Table Info

Table 1.

Previous studies of anti-CD16 × IL-15 TriKEs with different specificity in various cancer models

Antibody format	Ligand specificity	Tumor type	Target model	References
scFv-IL-scFv	CD33	Hematologic malignancy	AML	[7]
scFv-IL-scFv	EpCAM	Carcinomas	Carcinomas	[13]
scFv-IL-scFv	CD133	Solid tumor and hematologic malignancy	Colorectal carcinoma and Burkitt lymphoma	[14]
scFv-IL-scFv	CD19	Hematologic malignancy	B-CLL CD19⁺ tumor	[15]
scFv-IL-scFv	CD19	Hematologic malignancy	CD19⁺ tumor	[16]
sdAb-IL-scFv	B7-H3	Solid tumor	Ovarian cancer	[20]
sdAb-IL-scFv	CD33	Hematologic malignancy	AML	[25]
sdAb-IL-scFv	HER2	Solid tumor	Ovarian cancer	[26]
sdAb-IL-scFv	CLEC12A	Hematologic malignancy	AML	[9]
sdAb-IL-scFv	TEM8	Solid tumor	NSCLC	[10]
sdAb-IL-scFv	Mesothelin	Solid tumor	NSCLC	[27]
sdAb-IL-scFv	BCMA	Hematologic malignancy	MM	[11]

EpCAM: epithelial cell adhesion molecule; AML: acute myeloid leukemia; B-CLL: B cell chronic lymphocytic leukemia; NSCLC: non-small cell lung cancer; MM: multiple myeloma; HER2: human epidermal growth factor receptor 2; CLEC12A: C-type lectin domain family 12 member A; B7-H3: B7 homolog 3; BCMA: B-cell maturation antigen; TEM8: tumor endothelial marker 8

Declarations

Author contributions

PW: Conceptualization, Writing—original draft, Writing—review & editing. AP: Writing—review & editing, Supervision. SO: Writing—review & editing, Validation, Supervision. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Cancer today [Internet]. Lyon, France: IARC; c1965-2024 [cited 2023 Sep 30]. Available from: https://gco.iarc.fr/today

Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48. [DOI] [PubMed]

Facts: updated data on blood cancers [Internet]. LLS; c2015 [cited 2023 Dec 1]. Available from: https://www.lls.org/booklet/facts-updated-data-blood-cancers

Malvezzi M, Santucci C, Boffetta P, Collatuzzo G, Levi F, La Vecchia C, et al. European cancer mortality predictions for the year 2023 with focus on lung cancer. Ann Oncol. 2023;34:410–9. [DOI] [PubMed]

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7–33. [DOI] [PubMed]

Huang J, Ngai CH, Deng Y, Tin MS, Lok V, Zhang L, et al. Cancer incidence and mortality in Asian countries: a trend analysis. Cancer Control. 2022;29. [DOI] [PubMed] [PMC]

Vallera DA, Felices M, McElmurry R, McCullar V, Zhou X, Schmohl JU, et al. IL15 trispecific killer engagers (TriKE) make natural killer cells specific to CD33⁺ targets while also inducing persistence, in vivo expansion, and enhanced function. Clin Cancer Res. 2016;22:3440–50. [DOI] [PubMed] [PMC]

Mei XB, Yang J. Novel strategies for redirecting NK cells in cancer immunotherapy. J Nutr Onco. 2017;2:66–72.

Arvindam US, van Hauten PMM, Schirm D, Schaap N, Hobo W, Blazar BR, et al. A trispecific killer engager molecule against CLEC12A effectively induces NK-cell mediated killing of AML cells. Leukemia. 2021;35:1586–96. [DOI] [PubMed] [PMC]

10.

Kaminski MF, Bendzick L, Hopps R, Kauffman M, Kodal B, Soignier Y, et al. TEM8 tri-specific killer engager binds both tumor and tumor stroma to specifically engage natural killer cell anti-tumor activity. J Immunother Cancer. 2022;10:e004725. [DOI] [PubMed] [PMC]

11.

Oh F, Felices M, Kodal B, Miller JS, Vallera DA. Immunotherapeutic development of a tri-specific NK cell engager recognizing BCMA. Immuno. 2023;3:237–49. [DOI]

12.

Felices M, Warlick E, Juckett M, Weisdorf D, Vallera D, Miller S, et al. 444 GTB-3550 tri-specific killer engager TriKE™ drives NK cells expansion and cytotoxicity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients. J Immunother Cancer. 2021;9:A473. [DOI]

13.

Schmohl JU, Felices M, Taras E, Miller JS, Vallera DA. Enhanced ADCC and NK cell activation of an anticarcinoma bispecific antibody by genetic insertion of a modified IL-15 cross-linker. Mol Ther. 2016;24:1312–22. [DOI] [PubMed] [PMC]

14.

Schmohl JU, Felices M, Oh F, Lenvik AJ, Lebeau AM, Panyam J, et al. Engineering of anti-CD133 trispecific molecule capable of inducing NK expansion and driving antibody-dependent cell-mediated cytotoxicity. Cancer Res Treat. 2017;49:1140–52. [DOI] [PubMed] [PMC]

15.

Felices M, Kodal B, Hinderlie P, Kaminski MF, Cooley S, Weisdorf DJ, et al. Novel CD19-targeted TriKE restores NK cell function and proliferative capacity in CLL. Blood Adv. 2019;3:897–907. [DOI] [PubMed] [PMC]

16.

Cheng Y, Zheng X, Wang X, Chen Y, Wei H, Sun R, et al. Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers. Cancer Biol Med. 2020;17:1026–38. [DOI] [PubMed] [PMC]

17.

Behar G, Sibéril S, Groulet A, Chames P, Pugnière M, Boix C, et al. Isolation and characterization of anti-FcγRIII (CD16) llama single-domain antibodies that activate natural killer cells. Protein Eng Des Sel. 2008;21:1–10. [DOI] [PubMed]

18.

Vincke C, Loris R, Saerens D, Martinez-Rodriguez S, Muyldermans S, Conrath K. General strategy to humanize a camelid single-domain antibody and identification of a universal humanized nanobody scaffold. J Biol Chem. 2009;284:3273–84. [DOI] [PubMed]

19.

Glorius P, Baerenwaldt A, Kellner C, Staudinger M, Dechant M, Stauch M, et al. The novel tribody [(CD20)2xCD16] efficiently triggers effector cell-mediated lysis of malignant B cells. Leukemia. 2013;27:190–201. [DOI] [PubMed]

20.

Vallera DA, Ferrone S, Kodal B, Hinderlie P, Bendzick L, Ettestad B, et al. NK-cell-mediated targeting of various solid tumors using a B7-H3 tri-specific killer engager in vitro and in vivo. Cancers (Basel). 2020;12:2659. [DOI] [PubMed] [PMC]

21.

Paul S, Lal G. The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front Immunol. 2017;8:1124. [DOI] [PubMed] [PMC]

22.

Tapia-Galisteo A, Compte M, Álvarez-Vallina L, Sanz L. When three is not a crowd: trispecific antibodies for enhanced cancer immunotherapy. Theranostics. 2023;13:1028–41. [DOI] [PubMed] [PMC]

23.

Maali A, Gholizadeh M, Feghhi-Najafabadi S, Noei A, Seyed-Motahari SS, Mansoori S, et al. Nanobodies in cell-mediated immunotherapy: on the road to fight cancer. Front Immunol. 2023;14:1012841. [DOI] [PubMed] [PMC]

24.

Zhu X, Marcus WD, Xu W, Lee HI, Han K, Egan JO, et al. Novel human interleukin-15 agonists. J Immunol. 2009;183:3598–607. [DOI] [PubMed] [PMC]

25.

Felices M, Lenvik TR, Kodal B, Lenvik AJ, Hinderlie P, Bendzick LE, et al. Potent cytolytic activity and specific IL15 delivery in a second-generation trispecific killer engager. Cancer Immunol Res. 2020;8:1139–49. [DOI] [PubMed] [PMC]

26.

Vallera DA, Oh F, Kodal B, Hinderlie P, Geller MA, Miller JS, et al. A HER2 tri-specific NK cell engager mediates efficient targeting of human ovarian cancer. Cancers (Basel). 2021;13:3994. [DOI] [PubMed] [PMC]

27.

Kennedy PR, Vallera DA, Ettestad B, Hallstrom C, Kodal B, Todhunter DA, et al. A tri-specific killer engager against mesothelin targets NK cells towards lung cancer. Front Immunol. 2023;14:1060905. [DOI] [PubMed] [PMC]

28.

Zhang J, Zheng H, Diao Y. Natural killer cells and current applications of chimeric antigen receptor-modified NK-92 cells in tumor immunotherapy. Int J Mol Sci. 2019;20:317. [DOI] [PubMed] [PMC]

29.

Liu S, Galat V, Galat Y, Lee YKA, Wainwright D, Wu J. NK cell-based cancer immunotherapy: from basic biology to clinical development. J Hematol Oncol. 2021;14:7. [DOI] [PubMed] [PMC]

30.

Terren I, Orrantia A, Vitalle J, Zenarruzabeitia O, Borrego F. NK cell metabolism and tumor microenvironment. Front Immunol. 2019;10:2278. [DOI] [PubMed] [PMC]

31.

Alter G, Malenfant JM, Altfeld M. CD107a as a functional marker for the identification of natural killer cell activity. J Immunol Methods. 2004;294:15–22. [DOI] [PubMed]

32.

Davies JOJ, Stringaris K, Barrett AJ, Rezvani K. Opportunities and limitations of natural killer cells as adoptive therapy for malignant disease. Cytotherapy. 2014;16:1453–66. [DOI] [PubMed] [PMC]

33.

Prager I, Watzl C. Mechanisms of natural killer cell-mediated cellular cytotoxicity. J Leukoc Biol. 2019;105:1319–29. [DOI] [PubMed]

34.

Li H, Feng Y, Luo Q, Li Z, Li X, Gan H, et al. Stimuli-activatable nanomedicine meets cancer theranostics. Theranostics. 2023;13:5386–417. [DOI] [PubMed] [PMC]

35.

Huang L, Zhu J, Xiong W, Feng J, Yang J, Lu X, et al. Tumor-generated reactive oxygen species storm for high-performance ferroptosis therapy. ACS Nano. 2023;17:11492–506. [DOI] [PubMed]

36.

Melaiu O, Lucarini V, Cifaldi L, Fruci D. Influence of the tumor microenvironment on NK cell function in solid tumors. Front Immunol. 2019;10:3038. [DOI] [PubMed] [PMC]

37.

Nakamura K, Matsunaga K. Susceptibility of natural killer (NK) cells to reactive oxygen species (ROS) and their restoration by the mimics of superoxide dismutase (SOD). Cancer Biother Radiopharm. 1998;13:275–90. [DOI] [PubMed]

38.

Garofalo C, De Marco C, Cristiani CM. NK cells in the tumor microenvironment as new potential players mediating chemotherapy effects in metastatic melanoma. Front Oncol. 2021;11:754541. [DOI] [PubMed] [PMC]

39.

Zhou Y, Cheng L, Liu L, Li X. NK cells are never alone: crosstalk and communication in tumour microenvironments. Mol Cancer. 2023;22:34. [DOI] [PubMed] [PMC]

40.

Zahavi D, Weiner L. Monoclonal antibodies in cancer therapy. Antibodies (Basel). 2020;9:34. [DOI] [PubMed] [PMC]

41.

Felices M, Lenvik TR, Davis ZB, Miller JS, Vallera DA. Generation of BiKEs and TriKEs to improve NK cell-mediated targeting of tumor cells. Methods Mol Biol. 2016;1441:333–46. [DOI] [PubMed] [PMC]

42.

Hallett WHD, Ames E, Alvarez M, Barao I, Taylor PA, Blazar BR, et al. Combination therapy using IL-2 and anti-CD25 results in augmented natural killer cell-mediated antitumor responses. Biol Blood Marrow Transplant. 2008;14:1088–99. [DOI] [PubMed] [PMC]

43.

Abbas AK. The surprising story of IL-2: from experimental models to clinical application. Am J Pathol. 2020;190:1776–81. [DOI] [PubMed]

44.

Guan H, Nagarkatti PS, Nagarkatti M. Blockade of hyaluronan inhibits IL-2-induced vascular leak syndrome and maintains effectiveness of IL-2 treatment for metastatic melanoma. J Immunol. 2007;179:3715–23. [DOI] [PubMed]

45.

Miyazato K, Hayakawa Y. Pharmacological targeting of natural killer cells for cancer immunotherapy. Cancer Sci. 2020;111:1869–75. [DOI] [PubMed] [PMC]

46.

Conlon KC, Miljkovic MD, Waldmann TA. Cytokines in the treatment of cancer. J Interferon Cytokine Res. 2019;39:6–21. [DOI] [PubMed] [PMC]

47.

Bogen JP, Carrara SC, Fiebig D, Grzeschik J, Hock B, Kolmar H. Design of a trispecific checkpoint inhibitor and natural killer cell engager based on a 2 + 1 common light chain antibody architecture. Front Immunol. 2021;12:669496. [DOI] [PubMed] [PMC]

48.

Benmebarek MR, Karches CH, Cadilha BL, Lesch S, Endres S, Kobold S. Killing mechanisms of chimeric antigen receptor (CAR) T cells. Int J Mol Sci. 2019;20:1283. [DOI] [PubMed] [PMC]

49.

Messmer AS, Que YA, Schankin C, Banz Y, Bacher U, Novak U, et al. CAR T-cell therapy and critical care. Wien Klin Wochenschr. 2021;133:1318–25. [DOI] [PubMed] [PMC]

50.

Kochenderfer JN, Rosenberg SA. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol. 2013;10:267–76. [DOI] [PubMed] [PMC]

51.

Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, et al. KTE-X19 CAR T-Cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382:1331–42. [DOI] [PubMed] [PMC]

52.

Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531–44. [DOI] [PubMed] [PMC]

53.

Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–48. [DOI] [PubMed] [PMC]

54.

Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak O, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017;377:2545–54. [DOI] [PubMed] [PMC]

55.

Mitra A, Barua A, Huang L, Ganguly S, Feng Q, He B. From bench to bedside: the history and progress of CAR T cell therapy. Front Immunol. 2023;14:1188049. [DOI] [PubMed] [PMC]

56.

Sun S, Hao H, Yang G, Zhang Y, Fu Y. Immunotherapy with CAR-modified T cells: toxicities and overcoming strategies. J Immunol Res. 2018;2018:2386187. [DOI] [PubMed] [PMC]

57.

Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11:69. [DOI] [PubMed] [PMC]

58.

Bugelski PJ, Achuthanandam R, Capocasale RJ, Treacy G, Bouman-Thio E. Monoclonal antibody-induced cytokine-release syndrome. Expert Rev Clin Immunol. 2009;5:499–521. [DOI] [PubMed]

59.

Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124:188–95. Erratum in: Blood. 2015;126:1048. [DOI] [PubMed] [PMC]

60.

Fitzgerald JC, Weiss SL, Maude SL, Barrett DM, Lacey SF, Melenhorst JJ, et al. Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia. Crit Care Med. 2017;45:e124–31. [DOI] [PubMed] [PMC]

61.

Sterner RM, Kenderian SS. Myeloid cell and cytokine interactions with chimeric antigen receptor-T-cell therapy: implication for future therapies. Curr Opin Hematol. 2020;27:41–8. [DOI] [PubMed]

62.

Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7:303ra139. [DOI] [PubMed] [PMC]

63.

Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J Med. 2011;364:1844–54. [DOI] [PubMed] [PMC]

64.

Lo Nigro C, Macagno M, Sangiolo D, Bertolaccini L, Aglietta M, Merlano MC. NK-mediated antibody-dependent cell-mediated cytotoxicity in solid tumors: biological evidence and clinical perspectives. Ann Transl Med. 2019;7:105. [DOI] [PubMed] [PMC]

65.

Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN. Clinical use of dendritic cells for cancer therapy. Lancet Oncol. 2014;15:e257–67. [DOI] [PubMed]

66.

Franzin R, Netti GS, Spadaccino F, Porta C, Gesualdo L, Stallone G, et al. The use of immune checkpoint inhibitors in oncology and the occurrence of AKI: where do we stand? Front Immunol. 2020;11:574271. [DOI] [PubMed] [PMC]

67.

Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271:1734–6. [DOI] [PubMed]

68.

van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (Gm-Csf)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med. 1999;190:355–66. [DOI] [PubMed] [PMC]

69.

Sullivan RJ, Weber JS. Immune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies. Nat Rev Drug Discov. 2022;21:495–508. [DOI] [PubMed]

70.

Wang SJ, Dougan SK, Dougan M. Immune mechanisms of toxicity from checkpoint inhibitors. Trends Cancer. 2023;9:543–53. [DOI] [PubMed]

71.

Johnson DB, Nebhan CA, Moslehi JJ, Balko JM. Immune-checkpoint inhibitors: long-term implications of toxicity. Nat Rev Clin Oncol. 2022;19:254–67. [DOI] [PubMed] [PMC]

72.

Baldo BA. Side effects of cytokines approved for therapy. Drug Saf. 2014;37:921–43. [DOI] [PubMed] [PMC]

73.

Sleijfer S, Bannink M, Van Gool AR, Kruit WH, Stoter G. Side effects of interferon-α therapy. Pharm World Sci. 2005;27:423–31. [DOI] [PubMed]

74.

Tay SS, Carol H, Biro M. TriKEs and BiKEs join CARs on the cancer immunotherapy highway. Hum Vaccin Immunother. 2016;12:2790–6. [DOI] [PubMed] [PMC]

75.

Descotes J. Immunotoxicity of monoclonal antibodies. MAbs. 2009;1:104–11. [DOI] [PubMed] [PMC]

76.

Le Basle Y, Chennell P, Tokhadze N, Astier A, Sautou V. Physicochemical stability of monoclonal antibodies: a review. J Pharm Sci. 2020;109:169–90. [DOI] [PubMed]

77.

Brennan FR, Morton LD, Spindeldreher S, Kiessling A, Allenspach R, Hey A, et al. Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies. MAbs. 2010;2:233–55. [DOI] [PubMed] [PMC]

78.

Cruz E, Kayser V. Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy. Biologics. 2019;13:33–51. [DOI] [PubMed] [PMC]

79.

Ceschi A, Noseda R, Palin K, Verhamme K. Immune checkpoint inhibitor-related cytokine release syndrome: analysis of WHO global pharmacovigilance database. Front Pharmacol. 2020;11:557. [DOI] [PubMed] [PMC]

80.

Zhao Z, Zhang C, Zhou L, Dong P, Shi L. Immune checkpoint inhibitors and neurotoxicity. Curr Neuropharmacol. 2021;19:1246–63. [DOI] [PubMed] [PMC]

81.

Asaadi Y, Jouneghani FF, Janani S, Rahbarizadeh F. A comprehensive comparison between camelid nanobodies and single chain variable fragments. Biomark Res. 2021;9:87. [DOI] [PubMed] [PMC]

82.

Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836–47. [DOI] [PubMed] [PMC]

83.

Allen C, Zeidan AM, Bewersdorf JP. BiTEs, DARTS, BiKEs and TriKEs—are antibody based therapies changing the future treatment of AML? Life (Basel). 2021;11:465. [DOI] [PubMed] [PMC]

84.

Schmohl JU, Felices M, Todhunter D, Taras E, Miller JS, Vallera DA. Tetraspecific scFv construct provides NK cell mediated ADCC and self-sustaining stimuli via insertion of IL-15 as a cross-linker. Oncotarget. 2016;7:73830–44. [DOI] [PubMed] [PMC]

85.

Zhao X, Pan X, Wang Y, Zhang Y. Targeting neoantigens for cancer immunotherapy. Biomark Res. 2021;9:61. [DOI] [PubMed] [PMC]

86.

Ma W, Pham B, Li T. Cancer neoantigens as potential targets for immunotherapy. Clin Exp Metastasis. 2022;39:51–60. [DOI] [PubMed] [PMC]

87.

Wathikthinnakon M, Luangwattananun P, Sawasdee N, Chiawpanit C, Lee VS, Nimmanpipug P, et al. Combination gemcitabine and PD-L1xCD3 bispecific T cell engager (BiTE) enhances T lymphocyte cytotoxicity against cholangiocarcinoma cells. Sci Rep. 2022;12:6154. [DOI] [PubMed] [PMC]

88.

Hu Z, Xu X, Wei H. The adverse impact of tumor microenvironment on NK-cell. Front Immunol. 2021;12:633361. [DOI] [PubMed] [PMC]

89.

Romee R, Foley B, Lenvik T, Wang Y, Zhang B, Ankarlo D, et al. NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17). Blood. 2013;121:3599–608. [DOI] [PubMed] [PMC]

90.

Wang H, Zhang X, Wald D, Gong S, Wang W, Wang J. Downregulation of CD16 surface expression on NK cells is a favorable prognostic factor in acute myeloid leukemia. Blood. 2022;140:11834–5. [DOI]

91.

Wensveen FM, Jelenčić V, Polić B. NKG2D: a master regulator of immune cell responsiveness. Front Immunol. 2018;9:441. [DOI] [PubMed] [PMC]

92.

Zhang C, Hu Y, Shi C. Targeting natural killer cells for tumor immunotherapy. Front Immunol. 2020;11:60. [DOI] [PubMed] [PMC]

93.

Balaian L, Ball ED. Anti-CD33 monoclonal antibodies enhance the cytotoxic effects of cytosine arabinoside and idarubicin on acute myeloid leukemia cells through similarities in their signaling pathways. Exp Hematol. 2005;33:199–211. [DOI] [PubMed]

94.

Reusing SB, Vallera DA, Manser AR, Vatrin T, Bhatia S, Felices M, et al. CD16xCD33 bispecific killer cell engager (BiKE) as potential immunotherapeutic in pediatric patients with AML and biphenotypic ALL. Cancer Immunol Immunother. 2021;70:3701–8. [DOI] [PubMed] [PMC]

95.

Wang X, Lu P, Zhu L, Qin L, Zhu Y, Yan G, et al. Anti-CD133 antibody-targeted therapeutic immunomagnetic albumin microbeads loaded with vincristine-assisted to enhance anti-glioblastoma treatment. Mol Pharm. 2019;16:4582–93. [DOI] [PubMed]

96.

Jiang Z, Sun H, Yu J, Tian W, Song Y. Targeting CD47 for cancer immunotherapy. J Hematol Oncol. 2021;14:180. [DOI] [PubMed] [PMC]

97.

Zhang C, Röder J, Scherer A, Bodden M, Pfeifer Serrahima J, Bhatti A, et al. Bispecific antibody-mediated redirection of NKG2D-CAR natural killer cells facilitates dual targeting and enhances antitumor activity. J Immunother Cancer. 2021;9:e002980. [DOI] [PubMed] [PMC]