Cellular Immunotherapy for Cervical Cancer: Next Therapeutics Frontiers

Cervical cancer, particularly its advanced stages, requires novel therapeutic paradigms. Cellular immunotherapy exploits the constitutive expression of HPV E6/E7 oncoproteins as near-ideal tumor-specific antigens. This review systematically evaluates four principal platforms under investigation: tumor-infiltrating lymphocytes (TILs), TCR-engineered T cells, CAR-T cells, and CAR-NK cells. We critically analyze the preclinical rationale, clinical trial landscape, safety considerations, and manufacturing challenges for each modality. TIL therapy has achieved durable complete responses and an FDA Breakthrough Therapy designation. TCR-T cells enable precise targeting of intracellular viral epitopes but are HLA-restricted. CAR-T cells offer potent, MHC-independent recognition, yet face on-target/off-tumor toxicity and a suppressive tumor microenvironment. CAR-NK cells present a favorable safety profile and off-the-shelf potential. We conclude that the future of this field lies in rational combination strategies (e.g., with immune checkpoint blockade) and next-generation engineering (e.g., armored CARs, logic gates, allogeneic platforms) to overcome manufacturing complexity, toxicity, and high costs. Overcoming these barriers is essential to extend these therapies to resource-limited settings where the burden of cervical cancer is highest.