ALT-801 + cisplatin + gemcitabine

**ALT-801 + cisplatin + gemcitabine** is an experimental anti-cancer combination regimen consisting of three agents: - ALT-801, a bifunctional recombinant fusion protein combining interleukin-2 (IL-2) and a single-chain T cell receptor (scTCR) domain that specifically targets the p53 (aa264-272)/HLA-A*0201 peptide complex on tumor cells, thereby focusing immune activation on p53-positive, HLA-A*0201-positive cancers. ALT-801 induces the proliferation and activation of both CD4+ and CD8+ T cells as well as repolarization of tumor-associated macrophages (TAMs) from an M2 (tumor-promoting) to M1 (tumor-killing) phenotype, principally via interferon-gamma (IFN-γ) signaling. - Cisplatin and gemcitabine are chemotherapeutic agents; cisplatin is a platinum-based DNA crosslinker, and gemcitabine is a nucleoside analog inhibiting DNA synthesis. Preclinical studies suggest cisplatin may enhance p53 antigen presentation, thereby potentially increasing the effectiveness of ALT-801 immunotherapy in tumors by increasing p53 levels and thus the density of the ALT-801 target on cancer cells. This combination has been under phase 1 clinical evaluation in solid tumors including urothelial carcinoma and melanoma, but remains experimental[1][2].