eligibility_summary
Key eligibility: ≥21, consent, ECOG 0–1, life expectancy >12 wks, contraception, adequate hepatic/renal/lung/bone marrow, metastatic disease refractory to ≥2 lines, measurable disease, Vit D ≥20 ng/mL, NKG2D+ tumor. Exclusions: unresolved ≥G2 toxicity, unstable brain mets, uncontrolled disease/infection, HBV/HIV, major autoimmune, recent trials/surgery/radiation, cardiac issues/QTc>470, noncompliance. Withdraw for progression, illness, AEs, >4-wk delays, or patient choice.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Intervention: CTM-N2D, an allogeneic, mRNA-electroporated NKG2D-based CAR-grafted gamma-delta T-cell therapy. Mechanism: engineered gamma-delta T cells use a CAR with the NKG2D ectodomain to bind NKG2D ligands (MICA/B, ULBP1-6) broadly expressed on stressed tumor cells, while retaining native gamma-delta T-cell receptors (gamma-delta TCR, endogenous NKG2D, DNAM-1) to enhance recognition and cytotoxicity against stress-induced antigens. Adjuncts: lymphodepletion with fludarabine (antimetabolite) and cyclophosphamide (alkylator), zoledronic acid (bisphosphonate) pre-infusion to prime Vgamma9Vdelta2 cells, subcutaneous IL-2 (cytokine) post-infusion to support persistence. Targets/pathways: tumor cells expressing NKG2DL, NKG2D/NKG2DL axis and DNAM-1-mediated activation, potential off-tumor effects when NKG2DLs are stress-upregulated.