In Vivo Evaluation of Pam2Cys‐Modified Cancer‐Testis Antigens as Potential Self‐Adjuvanting Cancer Vaccines
Salwa Aljohani, Alex G. Edmonds, Valeria Castelletto, Jani Seitsonen, Ian W. Hamley, Peter Symonds, Victoria A. Brentville, Lindy G. Durrant, Nicholas J. Mitchell
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.
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…
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Taxonomy
TopicsImmunotherapy and Immune Responses · RNA Interference and Gene Delivery · vaccines and immunoinformatics approaches