Table Info

Table 2.

List of on-going nano based clinical trials for cancer immunotherapy

S. No	Title of the study	Nano-particle used	Target	Developer	Clinical stage	Clinical trial code/Ref
1	A randomized, double-blind, placebo controlled phase III study to investigate efficacy and safety of first-line treatment with HLX10 + chemotherapy (carboplatin-nanoparticle albumin bound (nab) paclitaxel) in patients with stage IIIB/IIIC or IV NSCLC	Albumin	Squamous non-small cell lung lancer	Shanghai Henlius Biotech	Phase 3	NCT04033354
2	A study to evaluate safety/tolerability of immunotherapy combinations in participants with triple-negative breast cancer or gynecologic malignancies	Albumin	Breast cancer, ovarian cancer	Arcus Biosciences, Inc., Infinity Pharmaceuticals, Inc.	Phase 1	NCT03719326
3	Bispecific antibody armed activated T-cells with aldesleukin and sargramostim in treating patients with locally advanced or metastatic pancreatic cancer	Albumin	Metastatic pancreatic adenocarcinoma, pancreatic carcinoma	Barbara Ann Karmanos Cancer Institute, National Cancer Institute (NCI)	Phase 1, 2	NCT02620865
4	NBTXR3 activated by radiation therapy for the treatment of locally advanced or borderline-resectable pancreatic cancer	Hafnium oxide	Borderline resectable pancreatic adenocarcinoma, locally advanced pancreatic ductal adenocarcinoma, resectable pancreatic ductal adenocarcinoma	M.D. Anderson Cancer Center, NCI	Phase 1	NCT04484909
5	Investigating the effects of Mikei® red reishi essence EX on the immune system of prostate cancer patients and patients with non-cancerous conditions of the prostate	Gold	Prostate cancer	Nikkei (Canada) Marketing Limited	NA	NCT03589781
6	IMX-110 in patients with advanced Solid tumors	NA	Solid tumor, advanced solid tumors, pancreatic cancer, breast cancer, ovarian oancer	Immix Biopharma Australia Pty Ltd, Immix Biopharma, Inc.	Phase 1, 2	NCT03382340

Declarations

Author contributions

SRKP designed the main theme of this review and involved in the development of a hypothesis. He collected the data and contributed to the writing of this review. CFR involved in the collection of data, development of the hypothesis, and drafting the tables. KS guided the design of this review and hypothesis. He edited the overall manuscript and authenticated the technical value of this manuscript.

Conflicts of interest

The authors declare that they have no conflict of interest in the publication.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

KS would like to acknowledge the financial support by Science and Engineering Research Board of India (EMR/2016/003035). CFR acknowledges Kalasalingam Academy of Research and Education for financial assistance in the form of Post-graduate Scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Hu T, Li Z, Gao CY, Cho CH. Mechanisms of drug resistance in colon cancer and its therapeutic strategies. World J Gastroenterol. 2016;22:6876–89. [DOI] [PubMed] [PMC]

Song W, Musetti SN, Huang L. Nanomaterials for cancer immunotherapy. Biomaterials. 2017;148:16–30. [DOI] [PubMed] [PMC]

Keogh E, Fikes J, Southwood S, Celis E, Chesnut R, Sette A. Identification of new epitopes from four different tumor-associated antigens: recognition of naturally processed epitopes correlates with HLA-A*0201-binding affinity. J Immunol. 2001;167:787–96. [DOI] [PubMed]

Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Sakaguchi K, Appella E, et al. Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection. Proc Natl Acad Sci U S A. 1994;91:6458–62. [DOI] [PubMed] [PMC]

Rosenberg SA. Cancer vaccines based on the identification of genes encoding cancer regression antigens. Immunol Today. 1997;18:175–82. [DOI] [PubMed]

Pule MA, Savoldo B, Myers GD, Rossig C, Russell H V, Dotti G, et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med. 2008;14:1264–70. [DOI] [PubMed] [PMC]

Louis CU, Savoldo B, Dotti G, Pule M, Yvon E, Myers GD, et al. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood. 2011;118:6050–6. [DOI] [PubMed] [PMC]

Brown CE, Alizadeh D, Starr R, Weng L, Wagner JR, Naranjo A, et al. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. N Engl J Med. 2016;375:2561–9. [DOI] [PubMed] [PMC]

Junghans RP, Ma Q, Rathore R, Gomes EM, Bais AJ, Lo ASY, et al. Phase I trial of anti-PSMA designer CAR-T cells in prostate cancer: possible role for interacting interleukin 2-T cell pharmacodynamics as a determinant of clinical response. Prostate. 2016;76:1257–70. [DOI] [PubMed]

10.

Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N Engl J Med. 2020;382:545–53. [DOI] [PubMed] [PMC]

11.

Xu J, Tian K, Zhang H, Li L, Liu H, Liu J, et al. Chimeric antigen receptor-T cell therapy for solid tumors require new clinical regimens. Expert Rev Anticancer Ther. 2017;17:1099–106. [DOI] [PubMed]

12.

Hariharan K, Braslawsky G, Black A, Raychaudhuri S, Hanna N. The induction of cytotoxic T cells and tumor regression by soluble antigen formulation. Cancer Res. 1995;55:3486–9. [PubMed]

13.

Slingluff CL Jr. The present and future of peptide vaccines for cancer: single or multiple, long or short, alone or in combination? Cancer J. 2011;17:343–50. [DOI] [PubMed] [PMC]

14.

Fadul CE, Fisher JL, Hampton TH, Lallana EC, Li Z, Gui J, et al. Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy. J Immunother. 2011;34:382–9. [DOI] [PubMed] [PMC]

15.

Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365:725–33. [DOI] [PubMed] [PMC]

16.

Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23. [DOI] [PubMed] [PMC]

17.

Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480:480–9. [DOI] [PubMed] [PMC]

18.

Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32. [DOI] [PubMed]

19.

Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–39. [DOI] [PubMed] [PMC]

20.

Prasad V, Kaestner V. Nivolumab and pembrolizumab: monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Semin Oncol. 2017;44:132–5. [DOI] [PubMed]

21.

Hoos A. Development of immuno-oncology drugs—from CTLA4 to PD1 to the next generations. Nat Rev Drug Discov. 2016;15:235–47. [DOI] [PubMed]

22.

Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol. 2016;13:273–90. [DOI] [PubMed] [PMC]

23.

Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 2012;12:265–77. [DOI] [PubMed] [PMC]

24.

Gajewski TF, Woo SR, Zha Y, Spaapen R, Zheng Y, Corrales L, et al. Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr Opin Immunol. 2013;25:268–76. [DOI] [PubMed]

25.

Muller AJ, Scherle PA. Targeting the mechanisms of tumoral immune tolerance with small-molecule inhibitors. Nat Rev Cancer. 2006;6:613–25. [DOI] [PubMed]

26.

Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2:751–60. [DOI] [PubMed]

27.

Mitragotri S, Anderson DG, Chen X, Chow EK, Ho D, Kabanov AV, et al. Accelerating the translation of nanomaterials in biomedicine. ACS Nano. 2015;9:6644–54. [DOI] [PubMed] [PMC]

28.

Weissig V, Pettinger TK, Murdock N. Nanopharmaceuticals (part 1): products on the market. Int J Nanomedicine. 2014;9:4357–73. [DOI] [PubMed] [PMC]

29.

Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm. 2008;5:505–15. [DOI] [PubMed] [PMC]

30.

Tang L, Yang X, Yin Q, Cai K, Wang H, Chaudhury I, et al. Investigating the optimal size of anticancer nanomedicine. Proc Natl Acad Sci U S A. 2014;111:15344–9. [DOI] [PubMed] [PMC]

31.

Yu H, Tang Z, Zhang D, Song W, Zhang Y, Yang Y, et al. Pharmacokinetics, biodistribution and in vivo efficacy of cisplatin loaded poly (L-glutamic acid)-g-methoxy poly (ethylene glycol) complex nanoparticles for tumor therapy. J Control Release. 2015;205:89–97. [DOI] [PubMed]

32.

Elamanchili P, Diwan M, Cao M, Samuel J. Characterization of poly (D, L-lactic-co-glycolic acid) based nanoparticulate system for enhanced delivery of antigens to dendritic cells. Vaccine. 2004;22:2406–12. [DOI] [PubMed]

33.

Neumann S, Young K, Compton B, Anderson R, Painter G, Hook S. Synthetic TRP2 long-peptide and α-galactosylceramide formulated into cationic liposomes elicit CD8⁺ T-cell responses and prevent tumour progression. Vaccine. 2015;33:5838–44. [DOI] [PubMed]

34.

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34. [DOI] [PubMed] [PMC]

35.

Jiang Y, Krishnan N, Zhou J, Chekuri S, Wei X, Kroll A V, et al. Engineered cell-membrane-coated nanoparticles directly present tumor antigens to promote anticancer immunity. Adv Mater. 2020;32:e2001808. [DOI] [PubMed] [PMC]

36.

Ou W, Thapa RK, Jiang L, Soe ZC, Gautam M, Chang JH, et al. Regulatory T cell-targeted hybrid nanoparticles combined with immuno-checkpoint blockage for cancer immunotherapy. J Control Release. 2018;281:84–96. [DOI] [PubMed]

37.

Schuster M, Nechansky A, Kircheis R. Cancer immunotherapy. Biotechnol J. 2006;1:138–47. [DOI] [PubMed]

38.

Marincola FM, Jaffee EM, Hicklin DJ, Ferrone S. Escape of human solid tumors from T-cell recognition: Molecular mechanisms and functional significance. Adv Immunol. 2000;74:181–273. [DOI] [PubMed]

39.

Ochsenbein AF, Sierro S, Odermatt B, Pericin M, Karrer U, Hermans J, et al. Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction. Nature. 2001;411:1058–64. [DOI] [PubMed]

40.

Tamada K, Geng D, Sakoda Y, Bansal N, Srivastava R, Li Z, et al. Redirecting gene-modified T cells toward various cancer types using tagged antibodies. Clin Cancer Res. 2012;18:6436–45. [DOI] [PubMed]

41.

Schlimper C, Hombach AA, Abken H, Schmidt-Wolf IGH. Improved activation toward primary colorectal cancer cells by antigen-specific targeting autologous cytokine-induced killer cells. Clin Dev Immunol. 2012;2012:238924. [DOI] [PubMed] [PMC]

42.

Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010;18:843–51. [DOI] [PubMed] [PMC]

43.

Hege KM, Bergsland EK, Fisher GA, Nemunaitis JJ, Warren RS, McArthur JG, et al. Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer. J Immunother cancer. 2017;5:22. [DOI] [PubMed] [PMC]

44.

Zhang C, Wang Z, Yang Z, Wang M, Li S, Li Y, et al. Phase I escalating-dose trial of CAR-T therapy targeting CEA+ metastatic colorectal cancers. Mol Ther. 2017;25:1248–58. [DOI] [PubMed] [PMC]

45.

Thistlethwaite FC, Gilham DE, Guest RD, Rothwell DG, Pillai M, Burt DJ, et al. The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity. Cancer Immunol Immunother. 2017;66:1425–36. [DOI] [PubMed] [PMC]

46.

Li Y, Duo Y, Bao S, He L, Ling K, Luo J, et al. EpCAM aptamer-functionalized polydopamine-coated mesoporous silica nanoparticles loaded with DM1 for targeted therapy in colorectal cancer. Int J Nanomedicine. 2017;12:6239–57. [DOI] [PubMed] [PMC]

47.

Zhang Q, Zhang H, Ding J, Liu H, Li H, Li H, et al. Combination therapy with EpCAM-CAR-NK-92 cells and regorafenib against human colorectal cancer models. J Immunol Res. 2018;2018:4263520. [DOI] [PubMed] [PMC]

48.

Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625–38. [DOI] [PubMed]

49.

Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014;6:224ra25. [DOI]

50.

Neelapu SS, Tummala S, Kebriaei P, Wierda W, Locke FL, Lin Y, et al. Toxicity management after chimeric antigen receptor T cell therapy: one size does not fit ‘ALL’. Nat Rev Clin Oncol. 2018;15:218. [DOI]

51.

Lanier LL. Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol. 2008;9:495–502. [DOI] [PubMed] [PMC]

52.

Wu J, Lanier LL. Natural killer cells and cancer. Adv Cancer Res. 2003;90:127–56. [DOI] [PubMed]

53.

López-Soto A, Gonzalez S, Smyth MJ, Galluzzi L. Control of metastasis by NK cells. Cancer Cell. 2017;32:135–54. [DOI] [PubMed]

54.

Souza-Fonseca-Guimaraes F, Cursons J, Huntington ND. The emergence of natural killer cells as a major target in cancer immunotherapy. Trends Immunol. 2019;40:142–58. [DOI] [PubMed]

55.

Burger MC, Zhang C, Harter PN, Romanski A, Strassheimer F, Senft C, et al. CAR-engineered NK cells for the treatment of glioblastoma: turning innate effectors into precision tools for cancer immunotherapy. Front Immunol. 2019;10:2683. [DOI] [PubMed] [PMC]

56.

Morvan MG, Lanier LL. NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer. 2016;16:7–19. [DOI] [PubMed]

57.

Ljunggren HG, Kärre K. In search of the ‘missing self’: MHC molecules and NK cell recognition. Immunol Today. 1990;11:237–44. [DOI] [PubMed]

58.

Brandstadter JD, Yang Y. Natural killer cell responses to viral infection. J Innate Immun. 2011;3:274–9. [DOI] [PubMed] [PMC]

59.

Wehner R, Dietze K, Bachmann M, Schmitz M. The bidirectional crosstalk between human dendritic cells and natural killer cells. J Innate Immun. 2011;3:258–63. [DOI] [PubMed]

60.

Shibuya A, Campbell D, Hannum C, Yssel H, Franz-Bacon K, McClanahan T, et al. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity. 1996;4:573–81. [DOI] [PubMed]

61.

Huang R, Wang X, Zhou Y, Xiao Y. RANKL-induced M1 macrophages are involved in bone formation. Bone Res. 2017;5:17019. [DOI] [PubMed] [PMC]

62.

Wang D, Lou J, Ouyang C, Chen W, Liu Y, Liu X, et al. Ras-related protein Rab10 facilitates TLR4 signaling by promoting replenishment of TLR4 onto the plasma membrane. Proc Natl Acad Sci. 2010;107:13806–11. [DOI] [PubMed] [PMC]

63.

Zhang C, Oberoi P, Oelsner S, Waldmann A, Lindner A, Tonn T, et al. Chimeric antigen receptor-engineered NK-92 cells: an off-the-shelf cellular therapeutic for targeted elimination of cancer cells and induction of protective antitumor immunity. Front Immunol. 2017;8:533. [DOI] [PubMed] [PMC]

64.

Walzer T, Dalod M, Robbins SH, Zitvogel L, Vivier E. Natural-killer cells and dendritic cells: “l’union fait la force.” Blood. 2005:2252–8. [DOI]

65.

Fernandez NC, Lozier A, Flament C, Ricciardi-Castagnoli P, Bellet D, Suter M, et al. Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med. 1999;5:405–11. [DOI] [PubMed]

66.

Veluchamy JP, Kok N, van der Vliet HJ, Verheul HMW, de Gruijl TD, Spanholtz J. The rise of allogeneic natural killer cells as a platform for cancer immunotherapy: recent innovations and future developments. Front Immunol. 2017;8:631. [DOI] [PubMed] [PMC]

67.

Liu E, Tong Y, Dotti G, Shaim H, Savoldo B, Mukherjee M, et al. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Leukemia. 2018;32:520–31. [DOI] [PubMed] [PMC]

68.

Poilil Surendran S, Moon MJ, Park R, Jeong YY. Bioactive nanoparticles for cancer immunotherapy. Int J Mol Sci. 2018;19:3877. [DOI]

69.

Fan Y, Moon JJ. Nanoparticle drug delivery systems designed to improve cancer vaccines and immunotherapy. Vaccines. 2015;3:662–85. [DOI] [PubMed] [PMC]

70.

Chithrani BD, Ghazani AA, Chan WCW. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 2006;6:662–8. [DOI] [PubMed]

71.

Bramwell VW, Perrie Y. Particulate delivery systems for vaccines: what can we expect? J Pharm Pharmacol. 2006;58:717–28. [DOI] [PubMed]

72.

Yan W, Chen W, Huang L. Mechanism of adjuvant activity of cationic liposome: phosphorylation of a MAP kinase, ERK and induction of chemokines. Mol Immunol. 2007;44:3672–81. [DOI] [PubMed]

73.

Yan W, Chen W, Huang L. Reactive oxygen species play a central role in the activity of cationic liposome based cancer vaccine. J Control Release. 2008;130:22–8. [DOI] [PubMed]

74.

Vangasseri DP, Cui Z, Chen W, Hokey DA, Falo LD Jr, Huang L. Immunostimulation of dendritic cells by cationic liposomes. Mol Membr Biol. 2006;23:385–95. [DOI] [PubMed]

75.

Kaur R, Bramwell VW, Kirby DJ, Perrie Y. Pegylation of DDA: TDB liposomal adjuvants reduces the vaccine depot effect and alters the Th1/Th2 immune responses. J Control release. 2012;158:72–7. [DOI] [PubMed]

76.

Tsai CC, Chang CH, Chen LC, Chang YJ, Lan KL, Wu YH, et al. Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice. Int J Nanomedicine. 2011;6:2607–19. [DOI] [PubMed] [PMC]

77.

Nakamura T, Yamazaki D, Yamauchi J, Harashima H. The nanoparticulation by octaarginine-modified liposome improves α-galactosylceramide-mediated antitumor therapy via systemic administration. J Control Release. 2013;171:216–24. [DOI] [PubMed]

78.

Patel JM, Vartabedian VF, Bozeman EN, Caoyonan BE, Srivatsan S, Pack CD, et al. Plasma membrane vesicles decorated with glycolipid-anchored antigens and adjuvants via protein transfer as an antigen delivery platform for inhibition of tumor growth. Biomaterials. 2016;74:231–44. [DOI] [PubMed] [PMC]

79.

McHugh RS, Nagarajan S, Wang YC, Sell KW, Selvaraj P. Proteintransferofglycosyl-phosphatidylinositol-B7-1 into tumor cell membranes: a novel approach to tumor immunotherapy. Cancer Res. 1999;59:2433–7. [PubMed]

80.

Molino NM, Neek M, Tucker JA, Nelson EL, Wang SW. Viral-mimicking protein nanoparticle vaccine for eliciting anti-tumor responses. Biomaterials. 2016;86:83–91. [DOI] [PubMed] [PMC]

81.

Kushnir N, Streatfield SJ, Yusibov V. Virus-like particles as a highly efficient vaccine platform: diversity of targets and production systems and advances in clinical development. Vaccine. 2012;31:58–83. [DOI] [PubMed] [PMC]

82.

Dewitte H, Van Lint S, Heirman C, Thielemans K, De Smedt SC, Breckpot K, et al. The potential of antigen and TriMix sonoporation using mRNA-loaded microbubbles for ultrasound-triggered cancer immunotherapy. J Control Release. 2014;194:28–36. [DOI] [PubMed]

83.

Bonehill A, Van Nuffel AMT, Corthals J, Tuyaerts S, Heirman C, François V, et al. Single-step antigen loading and activation of dendritic cells by mRNA electroporation for the purpose of therapeutic vaccination in melanoma patients. Clin Cancer Res. 2009;15:3366–75. [DOI] [PubMed]

84.

Shen L, Higuchi T, Tubbe I, Voltz N, Krummen M, Pektor S, et al. A trifunctional dextran-based nanovaccine targets and activates murine dendritic cells, and induces potent cellular and humoral immune responses in vivo. PLoS One. 2013;8:e80904. [DOI] [PubMed] [PMC]

85.

Broaders KE, Cohen JA, Beaudette TT, Bachelder EM, Fréchet JMJ. Acetalated dextran is a chemically and biologically tunable material for particulate immunotherapy. Proc Natl Acad Sci. 2009;106:5497–502. [DOI] [PubMed] [PMC]

86.

Zhang D, Wu T, Qin X, Qiao Q, Shang L, Song Q, et al. Intracellularly generated immunological gold nanoparticles for combinatorial photothermal therapy and immunotherapy against tumor. Nano Lett. 2019;19:6635–46. [DOI] [PubMed]

87.

Cho NH, Cheong TC, Min JH, Wu JH, Lee SJ, Kim D, et al. A multifunctional core-shell nanoparticle for dendritic cell-based cancer immunotherapy. Nat Nanotechnol. 2011;6:675–82. [DOI] [PubMed]

88.

Ong C, Cha BG, Kim J. Mesoporous silica nanoparticles doped with gold nanoparticles for combined cancer immunotherapy and photothermal therapy. ACS Appl Bio Mater. 2019;2:3630–8. [DOI]

89.

Leleux J, Roy K. Micro and nanoparticle-based delivery systems for vaccine immunotherapy: an immunological and materials perspective. Adv Healthc Mater. 2013;2:72–94. [DOI] [PubMed]

90.

Zhang C, Shi G, Zhang J, Song H, Niu J, Shi S, et al. Targeted antigen delivery to dendritic cell via functionalized alginate nanoparticles for cancer immunotherapy. J Control Release. 2017;256:170–81. [DOI] [PubMed]

91.

Silva JM, Videira M, Gaspar R, Préat V, Florindo HF. Immune system targeting by biodegradable nanoparticles for cancer vaccines. J Control release. 2013;168:179–99. [DOI] [PubMed]

92.

Shao K, Singha S, Clemente-Casares X, Tsai S, Yang Y, Santamaria P. Nanoparticle-based immunotherapy for cancer. ACS Nano. 2015;9:16–30. [DOI] [PubMed]

93.

Kasturi SP, Skountzou I, Albrecht RA, Koutsonanos D, Hua T, Nakaya HI, et al. Programming the magnitude and persistence of antibody responses with innate immunity. Nature. 2011;470:543–7. [DOI] [PubMed] [PMC]

94.

Querec TD, Akondy RS, Lee EK, Cao W, Nakaya HI, Teuwen D, et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol. 2009;10:116–25. [DOI] [PubMed] [PMC]

95.

Subbotin VM. Dendritic cell-based cancer immunotherapy: the stagnant approach and a theoretical solution. Drug Discov Today. 2014;19:834–7. [DOI] [PubMed]

96.

Scheicher C, Mehlig M, Dienes HP, Reske K. Uptake of bead-adsorbed versus soluble antigen by bone marrow derived dendritic cells triggers their activation and increases their antigen presentation capacity. Adv Exp Med Biol. 1995;378:253–5. [DOI] [PubMed]

97.

Nixon DF, Hioe C, Bian Z, Kuebler P, Li ML, Qiu H, et al. Synthetic peptides entrapped in microparticles can elicit cytotoxic T cell activity. Vaccine. 1996;14:1523–30. [DOI] [PubMed]

98.

Diwan M, Elamanchili P, Lane H, Gainer A, Samuel J. Biodegradable nanoparticle mediated antigen delivery to human cord blood derived dendritic cells for induction of primary T cell responses. J Drug Target. 2003;11:495–507. [DOI] [PubMed]

99.

Thiele L, Rothen-Rutishauser B, Jilek S, Wunderli-Allenspach H, Merkle HP, Walter E. Evaluation of particle uptake in human blood monocyte-derived cells in vitro. Does phagocytosis activity of dendritic cells measure up with macrophages? J Control Release. 2001;76:59–71. [DOI] [PubMed]

100.

Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707–12. [DOI] [PubMed]

101.

Disis ML, Gooley TA, Rinn K, Davis D, Piepkorn M, Cheever MA, et al. Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J Clin Oncol. 2002;20:2624–32. [DOI] [PubMed]

102.

Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92. [DOI] [PubMed]

103.

Wei H, Wang S, Zhang D, Hou S, Qian W, Li B, et al. Targeted delivery of tumor antigens to activated dendritic cells via CD11c molecules induces potent antitumor immunity in mice. Clin Cancer Res. 2009;15:4612–21. [DOI] [PubMed]

104.

Shukla S, Myers JT, Woods SE, Gong X, Czapar AE, Commandeur U, et al. Plant viral nanoparticles-based HER2 vaccine: Immune response influenced by differential transport, localization and cellular interactions of particulate carriers. Biomaterials. 2017;121:15–27. [DOI] [PubMed]

105.

Khaldoyanidi SK, Glinsky VV, Sikora L, Glinskii AB, Mossine VV, Quinn TP, et al. MDA-MB-435 human breast carcinoma cell homo-and heterotypic adhesion under flow conditions is mediated in part by Thomsen-Friedenreich antigen-galectin-3 interactions. J Biol Chem. 2003;278:4127–34. [DOI] [PubMed]

106.

Rao L, Yu G, Meng Q, Bu L, Tian R, Lin L, et al. Cancer cell membrane-coated nanoparticles for personalized therapy in patient-derived xenograft models. Adv Funct Mater. 2019;29:1905671. [DOI]

107.

Fang RH, Kroll A V, Gao W, Zhang L. Cell membrane coating nanotechnology. Adv Mater. 2018;30:e1706759. [DOI] [PubMed] [PMC]

108.

Zhang Q, Dehaini D, Zhang Y, Zhou J, Chen X, Zhang L, et al. Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis. Nat Nanotechnol. 2018;13:1182–90. [DOI] [PubMed]

109.

Hu CMJ, Fang RH, Wang KC, Luk BT, Thamphiwatana S, Dehaini D, et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature. 2015;526:118–21. [DOI] [PubMed] [PMC]

110.

Parodi A, Quattrocchi N, Van De Ven AL, Chiappini C, Evangelopoulos M, Martinez JO, et al. Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat Nanotechnol. 2013;8:61–8. [DOI] [PubMed] [PMC]

111.

Hu CMJ, Zhang L, Aryal S, Cheung C, Fang RH, Zhang L. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc Natl Acad Sci. 2011;108:109805. [DOI]

112.

Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011;364:2119–27. [DOI] [PubMed] [PMC]

113.

Hamdy S, Molavi O, Ma Z, Haddadi A, Alshamsan A, Gobti Z, et al. Co-delivery of cancer-associated antigen and Toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8+ T cell-mediated anti-tumor immunity. Vaccine. 2008;26:5046–57. [DOI] [PubMed]

114.

Xu Z, Ramishetti S, Tseng YC, Guo S, Wang Y, Huang L. Multifunctional nanoparticles co-delivering Trp2 peptide and CpG adjuvant induce potent cytotoxic T-lymphocyte response against melanoma and its lung metastasis. J Control Release. 2013;172:259–65. [DOI] [PubMed]

115.

Deng G, Sun Z, Li S, Peng X, Li W, Zhou L, et al. Cell-membrane immunotherapy based on natural killer cell membrane coated nanoparticles for the effective inhibition of primary and abscopal tumor growth. ACS Nano. 2018;12:12096–108. [DOI] [PubMed]

116.

Yang R, Xu J, Xu L, Sun X, Chen Q, Zhao Y, et al. Cancer cell membrane-coated adjuvant nanoparticles with mannose modification for effective anticancer vaccination. ACS Nano. 2018;12:5121–9. [DOI] [PubMed]

117.

Turtle CJ, Riddell SR. Artificial antigen presenting cells for use in adoptive immunotherapy. Cancer J. 2010;16:374–81. [DOI] [PubMed] [PMC]

118.

Eggermont LJ, Paulis LE, Tel J, Figdor CG. Towards efficient cancer immunotherapy: advances in developing artificial antigen-presenting cells. Trends Biotechnol. 2014;32:456–65. [DOI] [PubMed] [PMC]

119.

Fang RH, Zhang L. Nanoparticle-based modulation of the immune system. Annu Rev Chem Biomol Eng. 2016;7:305–26. [DOI] [PubMed]

120.

Gorbet MJ, Ranjan A. Cancer immunotherapy with immunoadjuvants, nanoparticles, and checkpoint inhibitors: recent progress and challenges in treatment and tracking response to immunotherapy. Pharmacol Ther. 2020;207:107456. [DOI] [PubMed] [PMC]

121.

Long G V, Atkinson V, Cebon JS, Jameson MB, Fitzharris BM, McNeil CM, et al. Standard-dose pembrolizumab in combination with reduced-dose ipilimumab for patients with advanced melanoma (KEYNOTE-029): an open-label, phase 1b trial. Lancet Oncol. 2017;18:1202–10. [DOI] [PubMed]

122.

Deeks ED. Pembrolizumab: a review in advanced melanoma. Drugs. 2016;76:375–86. [DOI] [PubMed]

123.

Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18:1182–91. [DOI] [PubMed] [PMC]

124.

Luo W, Wang Z, Tian P, Li W. Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. J Cancer Res Clin Oncol. 2018;144:1851–9. [DOI] [PubMed]

125.

Brower V. Anti-PD-L1 inhibitor durvalumab in bladder cancer. Lancet Oncol. 2016;17:e275. [DOI]

126.

Zheng P, Zhou Z. Human cancer immunotherapy with PD-1/PD-L1 blockade. Biomark Cancer. 2015;7 Suppl 2:15–8. [DOI] [PubMed] [PMC]

127.

Hargadon KM, Johnson CE, Williams CJ. Immune checkpoint blockade therapy for cancer: an overview of FDA-approved immune checkpoint inhibitors. Int Immunopharmacol. 2018;62:29–39. [DOI] [PubMed]

128.

Chen Q, Xu L, Liang C, Wang C, Peng R, Liu Z. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat Commun. 2016;7:13193. [DOI] [PubMed] [PMC]

129.

Traini G, Ruiz-de-Angulo A, Blanco-Canosa JB, Zamacola Bascarán K, Molinaro A, Silipo A, et al. Cancer Immunotherapy of TLR4 agonist-antigen constructs enhanced with pathogen-mimicking magnetite nanoparticles and checkpoint blockade of PD-L1. Small. 2019;15:e1803993. [DOI] [PubMed]

130.

van der Zanden SY, Luimstra JJ, Neefjes J, Borst J, Ovaa H. Opportunities for small molecules in cancer immunotherapy. Trends Immunol. 2020;41:493–511. [DOI] [PubMed]

131.

Smith M, García-Martínez E, Pitter MR, Fucikova J, Spisek R, Zitvogel L, et al. Trial watch: Toll-like receptor agonists in cancer immunotherapy. Oncoimmunology. 2018;7:e1526250. [DOI] [PubMed] [PMC]

132.

Guzik K, Zak KM, Grudnik P, Magiera K, Musielak B, Törner R, et al. Small-molecule inhibitors of the programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) interaction via transiently induced protein states and dimerization of PD-L1. J Med Chem. 2017;60:5857–67. [DOI] [PubMed]

133.

Ganesan A, Ahmed M, Okoye I, Arutyunova E, Babu D, Turnbull WL, et al. Comprehensive in vitro characterization of PD-L1 small molecule inhibitors. Sci Rep. 2019;9:1–19. [DOI] [PubMed] [PMC]

134.

Li SD, Huang L. Pharmacokinetics and biodistribution of nanoparticles. Mol Pharm. 2008;5:496–504. [DOI] [PubMed]

135.

Hashida M, Opanasopit P, Nishikawa M. Factors affecting drug and gene delivery: effects of interaction with blood components. Crit Rev Ther Drug Carr Syst. 2002;19:191–233. [DOI]

136.

Dobrovolskaia MA, McNeil SE. Immunological properties of engineered nanomaterials. Nat Nanotechnol. 2007;2:469–78. [DOI] [PubMed]

137.

Boraschi D, Costantino L, Italiani P. Interaction of nanoparticles with immunocompetent cells: nanosafety considerations. Nanomedicine. 2012;7:121–31. [DOI] [PubMed]

138.

Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 2003;425:516–21. [DOI] [PubMed]

139.

Maynard AD, Warheit DB, Philbert MA. The new toxicology of sophisticated materials: nanotoxicology and beyond. Toxicol Sci. 2011;120 Suppl 1:S109–29. [DOI] [PubMed] [PMC]

140.

Hegde PS, Chen DS. Top 10 challenges in cancer immunotherapy. Immunity. 2020;52:17–35. [DOI] [PubMed]

141.

Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027–34. [DOI] [PubMed] [PMC]

142.

Dong Y, Sun Q, Zhang X. PD-1 and its ligands are important immune checkpoints in cancer. Oncotarget. 2017;8:2171–86. [DOI] [PubMed] [PMC]

143.

Ebert PJR, Cheung J, Yang Y, McNamara E, Hong R, Moskalenko M, et al. MAP kinase inhibition promotes T cell and anti-tumor activity in combination with PD-L1 checkpoint blockade. Immunity. 2016;44:609–21. [DOI] [PubMed]

144.

Shrimali RK, Ahmad S, Verma V, Zeng P, Ananth S, Gaur P, et al. Concurrent PD-1 blockade negates the effects of OX40 agonist antibody in combination immunotherapy through inducing T-cell apoptosis. Cancer Immunol Res. 2017;5:755–66. [DOI] [PubMed]

145.

Dranoff G. Experimental mouse tumour models: what can be learnt about human cancer immunology? Nat Rev Immunol. 2012;12:61–6. [DOI]

146.

Gould SE, Junttila MR, de Sauvage FJ. Translational value of mouse models in oncology drug development. Nat Med. 2015;21:431–9. [DOI] [PubMed]

147.

Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–17. [DOI] [PubMed] [PMC]

148.

Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, et al. Overall survival and long-term safety of nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2015;33:2004–12. [DOI] [PubMed] [PMC]

149.

Irvine DJ, Dane EL. Enhancing cancer immunotherapy with nanomedicine. Nat Rev Immunol. 2020;5:321–34. [DOI]

150.

Shen CJ, Jameson KL, Weiss J, Hackman T, Dixon R, Akulian JA, et al. NANORAY-1100: a phase I study of NBTXR3 activated by radiotherapy in patients with advanced cancers treated with anti-PD-1 therapy. J Clin Oncol. 2020;38 Suppl 5:TPS86. [DOI]

151.

Kyte JA, Andresen NK, Russnes HG, Fretland SØ, Falk RS, Lingjærde OC, et al. ICON: a randomized phase IIb study evaluating immunogenic chemotherapy combined with ipilimumab and nivolumab in patients with metastatic hormone receptor positive breast cancer. J Transl Med. 2020;18:269. [DOI] [PubMed] [PMC]

152.

Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22. [DOI] [PubMed]

153.

Liu L, Zong ZM, Liu Q, Jiang SS, Zhang Q, Cen LQ, et al. A novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene delivery vector for immunotherapy of hepatocellular carcinoma. Biomaterials. 2018;184:20–30. [DOI] [PubMed]

154.

Jeanbart L, Kourtis IC, Van Der Vlies AJ, Swartz MA, Hubbell JA. 6-Thioguanine-loaded polymeric micelles deplete myeloid-derived suppressor cells and enhance the efficacy of T cell immunotherapy in tumor-bearing mice. Cancer Immunol Immunother. 2015;64:1033–46. [DOI] [PubMed] [PMC]

155.

Yim H, Park W, Kim D, Fahmy TM, Na K. A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers. Biomaterials. 2014;35:9912–9. [DOI] [PubMed]

156.

Garg SM, Vakili MR, Molavi O, Lavasanifar A. Self-Associating Poly (ethylene oxide)-block-poly (α-carboxyl-ε-caprolactone) drug conjugates for the delivery of STAT3 inhibitor JSI-124: potential application in cancer immunotherapy. Mol Pharm. 2017;14:2570–84. [DOI] [PubMed]

157.

Perica K, Tu A, Richter A, Bieler JG, Edidin M, Schneck JP. Magnetic field-induced T cell receptor clustering by nanoparticles enhances T cell activation and stimulates antitumor activity. ACS Nano. 2014;8:2252–60. [DOI] [PubMed] [PMC]

158.

Lu K, He C, Guo N, Chan C, Ni K, Weichselbaum RR, et al. Chlorin-based nanoscale metal-organic framework systemically rejects colorectal cancers via synergistic photodynamic therapy and checkpoint blockade immunotherapy. J Am Chem Soc. 2016;138:12502–10. [DOI] [PubMed] [PMC]

159.

Luo Z, Wang C, Yi H, Li P, Pan H, Liu L, et al. Nanovaccine loaded with poly I:C and STAT3 siRNA robustly elicits anti-tumor immune responses through modulating tumor-associated dendritic cells in vivo. Biomaterials. 2015;38:50–60. [DOI] [PubMed]

160.

Kwong B, Liu H, Irvine DJ. Induction of potent anti-tumor responses while eliminating systemic side effects via liposome-anchored combinatorial immunotherapy. Biomaterials. 2011;32:5134–47. [DOI] [PubMed] [PMC]

161.

Wang C, Zhuang Y, Zhang Y, Luo Z, Gao N, Li P, et al. Toll-like receptor 3 agonist complexed with cationic liposome augments vaccine-elicited antitumor immunity by enhancing TLR3-IRF3 signaling and type I interferons in dendritic cells. Vaccine. 2012;30:4790–9. [DOI] [PubMed]

162.

Van Broekhoven CL, Parish CR, Demangel C, Britton WJ, Altin JG. Targeting dendritic cells with antigen-containing liposomes: a highly effective procedure for induction of antitumor immunity and for tumor immunotherapy. Cancer Res. 2004;64:4357–65. [DOI] [PubMed]

163.

Wu C, Guan X, Xu J, Zhang Y, Liu Q, Tian Y, et al. Highly efficient cascading synergy of cancer photo-immunotherapy enabled by engineered graphene quantum dots/photosensitizer/CpG oligonucleotides hybrid nanotheranostics. Biomaterials. 2019;205:106–19. [DOI] [PubMed]

164.

Guo L, Yan DD, Yang D, Li Y, Wang X, Zalewski O, et al. Combinatorial photothermal and immuno cancer therapy using chitosan-coated hollow copper sulfide nanoparticles. ACS Nano. 2014;8:5670–81. [DOI] [PubMed] [PMC]

165.

Marrache S, Choi JH, Tundup S, Zaver D, Harn DA, Dhar S. Immune stimulating photoactive hybrid nanoparticles for metastatic breast cancer. Integr Biol. 2013;5:215–23. [DOI]

166.

Mejías R, Pérez-Yagüe S, Gutiérrez L, Cabrera LI, Spada R, Acedo P, et al. Dimercaptosuccinic acid-coated magnetite nanoparticles for magnetically guided in vivo delivery of interferon gamma for cancer immunotherapy. Biomaterials. 2011;32:2938–52. [DOI] [PubMed]

167.

Jang B, Xu L, Moorthy MS, Zhang W, Zeng L, Kang M, et al. Lipopolysaccharide-coated CuS nanoparticles promoted anti-cancer and anti-metastatic effect by immuno-photothermal therapy. Oncotarget. 2017;8:105584–95. [DOI] [PubMed] [PMC]

168.

Cano-Mejia J, Burga RA, Sweeney EE, Fisher JP, Bollard CM, Sandler AD, et al. Prussian blue nanoparticle-based photothermal therapy combined with checkpoint inhibition for photothermal immunotherapy of neuroblastoma. Nanomedicine Nanotechnology, Biol Med. 2017;13:771–81. [DOI]

169.

Yu X, Gao D, Gao L, Lai J, Zhang C, Zhao Y, et al. Inhibiting metastasis and preventing tumor relapse by triggering host immunity with tumor-targeted photodynamic therapy using photosensitizer-loaded functional nanographenes. ACS Nano. 2017;11:10147–58. [DOI] [PubMed]

170.

Duan X, Chan C, Guo N, Han W, Weichselbaum RR, Lin W. Photodynamic therapy mediated by nontoxic core-shell nanoparticles synergizes with immune checkpoint blockade to elicit antitumor immunity and antimetastatic effect on breast cancer. J Am Chem Soc. 2016;138:16686–95. [DOI] [PubMed] [PMC]

171.

Harini L, Srivastava S, Gnanakumar GP, Karthikeyan B, Ross C, Krishnakumar V, et al. An ingenious non-spherical mesoporous silica nanoparticle cargo with curcumin induces mitochondria-mediated apoptosis in breast cancer (MCF-7) cells. Oncotarget. 2019;10:1193–208. [DOI] [PubMed] [PMC]

172.

Ma W, Zhu D, Li J, Chen X, Xie W, Jiang X, et al. Coating biomimetic nanoparticles with chimeric antigen receptor T cell-membrane provides high specificity for hepatocellular carcinoma photothermal therapy treatment. Theranostics. 2020;10:1281–95. [DOI] [PubMed] [PMC]

173.

Xu J, Xu L, Wang C, Yang R, Zhuang Q, Han X, et al. Near-infrared-triggered photodynamic therapy with multitasking upconversion nanoparticles in combination with checkpoint blockade for immunotherapy of colorectal cancer. ACS Nano. 2017;11:4463–74. [DOI] [PubMed]