Clinical trial landscape and translational priorities for adoptive T-cell and NK-cell therapies in gynecologic malignancies.

Background: Adoptive T-cell and natural killer (NK)-cell therapies are expanding across solid tumors, but their registered development in gynecologic malignancies remains difficult to interpret because many studies use basket designs and registry records vary in detail. Methods: We conducted a cross-sectional analysis of therapeutic adoptive T-cell and NK-cell trial records identified from TrialTrove, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. Trials were classified into three mutually exclusive evidence-specificity groups: single gynecologic disease family specific, multiple gynecologic disease families only, and broader baskets including non-gynecologic cancers. We evaluated source sensitivity, target applicability, field-specific registry visibility, and the availability of posted registry safety results. A complementary registry-informed exploratory survey of 25 experts assessed translational barriers and development priorities using domain-specific 1-5 scales. Results: Among 442 unique records screened, 211 therapeutic trials met the eligibility criteria. Of these, 43 were restricted to a single gynecologic disease family, 2 included multiple gynecologic disease families only, and 166 were broader basket trials permitting enrollment of non-gynecologic malignancies. The public-registry-linked and public-search-captured sensitivity subsets included 200 and 141 records, respectively, with broadly similar structural patterns across datasets. The landscape was predominantly early phase, with 149 Phase I and 50 Phase I/II trials. CAR-T, TIL, and TCR-T were the leading modalities, accounting for 79, 60, and 42 trials, respectively. Only 20 records had posted registry results with an adverse-event module, indicating limited availability of registry-reported safety data. In the exploratory expert survey, an immunosuppressive tumor microenvironment and a lack of gynecologic-specific cohorts were identified as leading barriers, whereas ovarian cancer, TIL therapy, MSLN, target reporting, and registry completeness emerged as prominent development priorities. Conclusions: Registered cellular-therapy activity in gynecologic malignancies is broad but remains early phase, largely basket-derived, and unevenly visible in registry fields. Separating disease-specific trials from broader eligibility-only baskets, testing source sensitivity, and distinguishing modality biology from missing target reporting provide a more reproducible basis for future trial planning.