Immunotherapy has gathered significant attention and is now a widely used cancer treatment that uses the body’s immune system to fight cancer. Despite initial successes, its broader clinical application is hindered by limitations such as heterogeneity in patient response and challenges associated with the tumor immune microenvironment. Recent advancements in nanotechnology have offered innovative solutions to these barriers, providing significant enhancements to cancer immunotherapy. Nanotechnology-based approaches exhibit multifaceted mechanisms, including effective anti-tumor immune responses during tumorigenesis and overcoming immune suppression mechanisms to improve immune defense capacity. Nanomedicines, including nanoparticle-based vaccines, liposomes, immune modulators, and gene delivery systems, have demonstrated the ability to activate immune responses, modulate tumor microenvironments, and target specific immune cells. Success metrics in preclinical and early clinical studies, such as improved survival rates, enhanced tumor regression, and elevated immune activation indices, highlight the promise of these technologies. Despite these achievements, several challenges remain, including scaling up manufacturing, addressing off-target effects, and navigating regulatory complexities. The review emphasizes the need for interdisciplinary approaches to address these barriers, ensuring broader clinical adoption. It also provides insights into interdisciplinary approaches, advancements, and the transformative potential of nano-immunotherapy and promising results in checkpoint inhibitor delivery, nanoparticle-mediated photothermal therapy, immunomodulation as well as inhibition by nanoparticles and cancer vaccines.

Small cell lung cancer (SCLC) is an aggressive tumor characterized by early metastasis and resistance to treatment, making it a prime target for therapeutic investigation. The current standard of care for frontline treatment involves a combination of chemotherapeutic agents and immune checkpoint inhibitors (ICIs), though durability of response remains limited. The genetic heterogeneity of SCLC also complicates the development of new therapeutic options. Adoptive cell therapies show promise by targeting specific mutations in order to increase efficacy and minimize toxicity. There has been significant investigation in three therapeutic classes for application towards SCLC: antibody drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR)-T cell therapies. This review summarizes the recent advances and challenges in the development of adoptive cell therapies. Genetic targets such as delta-like ligand 3 (DLL3), trophoblast cell surface antigen 2 (Trop2), B7-H3 (CD276), gangliosides disialoganglioside GD2 (GD2) and ganglioside GM2 (GM2) have been found to be expressed in SCLC, which makes them prime targets for therapy development. While investigated therapies such as rovalpituzumab tesirine (Rova-T) have failed, several insights from these trials have led to the development of compelling new agents such as sacituzumab govitecan (SG), ifinatamab deruxtecan (I-DXd), tarlatamab, and DLL3-targeted CAR-T cells. Advancing development of molecular testing and improving targeted approaches remain integral to pushing forward the progress of adoptive cell therapies in SCLC.

Cervical cancer remains a significant global health challenge, ranking as the fourth most common cancer among women. Persistent infection with high-risk human papillomavirus (HPV) is the primary etiological factor, leading to immune evasion mechanisms that promote tumor development and progression. Immunotherapy has emerged as a transformative approach in the management of cervical cancer, aiming to restore and enhance the body’s immune response against tumor cells. Checkpoint inhibitors targeting programmed death-1 (PD-1) and its ligand (PD-L1) have shown promising results in patients with advanced or recurrent cervical cancer. Pembrolizumab, a PD-1 inhibitor, has been approved for PD-L1-positive cervical cancer, demonstrating durable responses. However, low response rates necessitate exploration of combination strategies. Trials are underway combining checkpoint inhibitors with chemotherapy, radiation, or other immunotherapeutic agents to enhance efficacy. Therapeutic vaccines targeting HPV antigens, such as E6 and E7 oncoproteins, are also a focus of active research. These vaccines aim to elicit robust cytotoxic T-cell responses, offering a potential strategy for early intervention and disease control. Adoptive T-cell therapies, including engineered T-cell receptor (TCR) and chimeric antigen receptor (CAR)-T cells, represent cutting-edge advancements, though challenges with tumor heterogeneity and off-target effects persist. However, challenges such as limited response rates and immune evasion mechanisms remain. The tumor microenvironment (TME) in cervical cancer, characterized by immunosuppressive cells and cytokines, poses a significant barrier to effective immunotherapy. Emerging approaches targeting the TME, such as cytokine modulation, hold promise in overcoming resistance mechanisms. Key gaps include a lack of biomarkers for patient selection, insufficient understanding of TME dynamics, and suboptimal strategies for overcoming antigen heterogeneity and immune resistance. This review addresses these issues by providing a comprehensive analysis of the current landscape of cervical cancer immunotherapy, identifying critical barriers, and highlighting emerging approaches, such as combination therapies, novel immune targets, and strategies to modulate the TME, to guide future research and clinical practice.