Breaking barriers in gynecologic malignancies with adoptive cell transfers and nanomedicine

Gynecologic cancers remain challenging malignancies to treat, with little improvement in survival outcomes since the introduction of platinum-based chemotherapy in the 1970s. These tumors are characterized by dense extracellular matrices, heterogeneous immune infiltrates, and immunosuppressive microenvironments that limit the success of standard therapies. Adoptive cell transfers (ACTs) have shown promise in overcoming these barriers, yet their development in gynecologic oncology lags behind that of other cancers. This perspective outlines factors contributing to this gap, current ACT approaches, including tumor-infiltrating lymphocytes, T-cell receptor-engineered T-cells, and chimeric antigen receptor cells, and evaluates their relevance in ovarian, endometrial, and cervical cancers. We highlight emergent strategies that integrate immune cell trafficking with biomaterials designed to improve localization, retention, and controlled drug release within tumors. We consider the relative advantages and limitations of each approach and offer practical considerations for developing these technologies to reshape clinical treatment paradigms for gynecologic cancers.