Homocitrullinated Binding immunoglobulin Protein peptide (Homocitrullinated BiP)

Homocitrullinated Binding immunoglobulin Protein (BiP) peptide is a stress-induced post-translationally modified (siPTM) antigen that serves as a target for cancer immunotherapy. BiP, also known as HSPA5 or GRP78, is an endoplasmic reticulum-resident chaperone protein that is significantly upregulated in cancer cells as part of the unfolded protein response to environmental stressors like hypoxia and nutrient deprivation (UniProt P11021; Brentville et al., 2020). Homocitrullination, also known as carbamylation, is a non-enzymatic modification where lysine residues are converted to homocitrulline by cyanate, a process that is enhanced in the inflammatory and stressful conditions of the tumor microenvironment (Brentville et al., 2021). These modified peptides are processed and presented on the cell surface via Major Histocompatibility Complex (MHC) class II molecules, where they can be recognized by CD4+ T-cells as foreign neoantigens (Scancell, 2024). Therapeutic vaccines, such as Scancell's Modi-1, incorporate homocitrullinated BiP peptides to stimulate a potent Th1-mediated immune response, leading to the destruction of tumor cells while potentially sparing normal tissues that do not present these modifications at high levels (Brentville et al., 2020). This target is particularly relevant for treating solid tumors, including triple-negative breast cancer, ovarian cancer, and pancreatic cancer, where BiP is highly expressed and modified (Scancell, 2024).

Other names

Carbamylated BiPHomocitrullinated HSPA5Homocitrullinated GRP78Carbamylated HSPA5Carbamylated GRP78Homocitrullinated 78 kDa glucose-regulated protein

Induction of CD4+ T-cell mediated immune response against cells presenting homocitrullinated peptides on MHC class II molecules.