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

## TL;DR

This study evaluates self-adjuvanting cancer vaccines by modifying cancer-testis antigens with Pam2Cys and testing them in vivo.

## Contribution

The novelty lies in covalently grafting Pam2Cys onto cancer-testis antigens to create self-adjuvanting vaccines.

## Key findings

- Pam2Cys-modified NY-ESO-1 and BAGE4 antigens were synthesized and tested in vivo.
- A lipid nanoparticle formulation of BAGE4 was also evaluated for its potential as a cancer vaccine.

## Abstract

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.

Peptide‐based vaccines, formulated with an appropriate adjuvant, offer a versatile platform for targeted cancer immunotherapy. Herein, we explore the synthesis of two tissue‐restricted cancer‐testis antigens; (NY‐ESO‐1 and BAGE4) covalently linked to the toll‐like receptor agonist, Pam2Cys. These constructs were evaluated in vivo along with a lipid nanoparticle formulation of BAGE4.