ALT-801 + cisplatin

ALT-801 + cisplatin is an experimental combination therapy for cancer, particularly under investigation for melanoma and urothelial cancer. ALT-801 is a bifunctional fusion protein consisting of interleukin-2 (IL-2) linked to a soluble, single-chain T cell receptor domain. This receptor recognizes a peptide epitope (amino acids 264-272) of the human p53 antigen presented by HLA-A*0201 on cancer cells. The rationale behind this combination is that chemotherapy agents like cisplatin can increase the expression of p53 in tumor cells, making them more susceptible to targeted immunotherapy by ALT-801. ALT-801 directs immune activation specifically to tumor cells overexpressing the p53/HLA-A*0201 complex, leading to the activation and proliferation of T cells and repolarization of tumor-associated macrophages, ultimately resulting in an antitumor immune response. Cisplatin is a well-established chemotherapy drug that induces DNA crosslinks and apoptosis, and can synergistically enhance p53 expression[1][2][4][6].