In Vivo Evaluation of Pam₂Cys-Modified Cancer-Testis Antigens as Potential Self-Adjuvanting Cancer Vaccines

Peptide-based vaccines, formulated with an appropriate adjuvant, offer a versatile platform for targeted cancer immunotherapy. While adjuvants are usually coadministered for nucleic acid and protein vaccines, synthetic peptide antigens afford a more effective opportunity to covalently and regioselectively graft immunostimulatory motifs directly onto the antigen scaffold to yield self-adjuvanting vaccines. Herein, we explore the synthesis of two tissue-restricted cancer-testis antigens (CTAs); New York oesophageal cell carcinoma 1 (NY-ESO-1) and B melanoma antigen 4 (BAGE4), both carrying the toll-like receptor (TLR) agonist, Pam₂Cys. These constructs were evaluated in vivo along with a lipid nanoparticle (LNP) preparation of the underexplored BAGE4 melanoma antigen.