Development of novel self-assembled vaccines based on tumour-specific antigenic peptide and TLR2 agonist for effective breast cancer immunotherapy via activating CD8+ T cells and enhancing their function

Abstract

Vaccines based on tumour-specific antigens are a promising approach for immunotherapy. However, the clinical efficacy of tumour-specific antigens is still challenging. Twelve conjugates with self-assembly properties were designed and synthesized using MAGE-A1 peptide and TLR2 agonist, combined with different covalent bonds. All the developed conjugates formed spherical nanoparticles with a diameter of approximately 150 nm, and enhanced the efficacy of the peptide vaccines with the better targeting of lymph nodes. All the conjugates could well bind to serum albumin and improve the plasma stability of the individual antigenic peptides. In particular, conjugate 6 (N-Ac PamCS-M-6) had a more significant ability to promote dendritic cell maturation, CD8⁺ T cell activation, and subsequent killing of tumour cells, with an in vivo tumour inhibition rate of 70 ± 2.9%. The interaction between specific response and the different conjugation modes was further explored, thereby providing a fundamental basis for novel immune anti-tumour molecular platforms.

Keywords: MAGE-A1; TLR2 agonist; conjugate; self-assembled; tumour vaccine.