Phase 1 TCR1188-ABC KRAS G12V TCR + ILT4 (LILRB2)–redirected base-edited T cells

This University of Pennsylvania first-in-human, Phase 1, open-label 3+3 dose-escalation study tests TCR1188-ABC: autologous CD4+ and CD8+ T cells that are base-edited and engineered to (1) express a high-affinity, HLA-A11:01–restricted T-cell receptor recognizing mutant KRAS G12V and (2) co-express an ILT4 (LILRB2)-binding scFv intended to redirect/engage ILT4-positive immunosuppressive myeloid cells in the tumor microenvironment. Patients receive lymphodepleting chemotherapy with fludarabine (a purine analog that blocks DNA synthesis) plus cyclophosphamide (an alkylating DNA crosslinker), followed by a single infusion of TCR1188-ABC cells; tocilizumab (IL-6 receptor–blocking monoclonal antibody, commonly used to manage CRS) is given per protocol. Eligible participants include metastatic KRAS G12V–mutant pancreatic adenocarcinoma, cholangiocarcinoma, colorectal cancer, or NSCLC, with HLA-A11:01 positivity and defined line-of-therapy minimums (e.g., later-line CRC). The key angle is combining neoantigen-precision TCR targeting (KRAS G12V) with a second “microenvironment” handle (ILT4/LILRB2), aiming to overcome myeloid-mediated resistance that often limits T-cell therapies in solid tumors; today’s care for these metastatic settings is sequential systemic therapy (platinum- and fluoropyrimidine-based chemo regimens, targeted agents when biomarkers fit, and immunotherapy in select groups), with limited durable options once standard lines fail.