pHLIP-SIINFEKL

pHLIP-SIINFEKL is an experimental peptide-drug conjugate (PDC) designed to artificially induce neoantigen expression in immunologically "cold" tumors to enhance their susceptibility to immunotherapy. The construct consists of a pH-low insertion peptide (pHLIP) conjugated to SIINFEKL, an immunogenic peptide derived from ovalbumin. pHLIP selectively targets and inserts into the membranes of cells within the acidic tumor microenvironment (TME), characteristic of the Warburg effect, delivering the SIINFEKL cargo intracellularly. Once inside the tumor cell, SIINFEKL is proteolytically processed and presented on the cell surface via the Major Histocompatibility Complex (MHC) class I pathway. This presentation "decorates" the tumor with a recognizable antigen, enabling SIINFEKL-specific CD8+ T cells (such as OT-I T cells) to identify and eliminate the tumor cells. Developed by researchers at Yale University, pHLIP-SIINFEKL has demonstrated the ability to suppress tumor growth and recruit activated T cells in preclinical models of melanoma, colon adenocarcinoma, and sarcoma.

Other names

pHLIP-peptide conjugate