Nitric oxide-modified tumor cell proteins

This target refers to the broad array of intracellular proteins within tumor cells that are modified ex vivo using nitric oxide (NO) donors, primarily through the process of S-nitrosylation of cysteine residues. This modification is utilized in the development of experimental cancer vaccines to enhance the immunogenicity of tumor cells (Shami et al., 2004, Leukemia Research). S-nitrosylation can lead to protein conformational changes, altered proteolytic processing, and the creation of neoepitopes, which help the immune system overcome self-tolerance to tumor antigens (ChEMBL, Target CHEMBL2111410). When these modified proteins are introduced back into the patient as a vaccine, they stimulate a robust T-cell response, specifically targeting both the modified and unmodified versions of these proteins on the surface of live tumor cells. This therapeutic strategy has been explored in preclinical and early clinical models for various malignancies, including melanoma and leukemia, aiming to provide a more potent immune stimulus than standard tumor cell lysates. The approach is designed to bypass the need for identifying specific single antigens by targeting the entire modified proteome of the cancer cell.

Other names

Intracellular proteins in tumor cells modified ex vivo by nitric oxideS-nitrosylated tumor cell proteinsNO-modified tumor cell antigensS-nitrosylated tumor cell lysate

Induction of T-cell mediated immune response against tumor-associated antigens enhanced by S-nitrosylation