Research Spotlight: A Potent Cancer Vaccine Adjuvant System for Particleization of Short, Synthetic CD8+ T Cell Epitopes

Posted on October 29, 2021

Graphical Abstract

How To Kill Cancer

To kill cancer cells, short-tumor-derived peptides (8-10 amino acids in length) must be recognized by the CD8+ T cell receptors. Short peptide epitopes are simple to produce and theoretically offer a means to induce CD8+ T cells against major histocompatibility complex I (MHC-1) antigen bearing target cells. This promising method for killing cancer cells has not produced the desired results in clinical studies.

How to Improve This Method for Treating Cancer

One suggested reason that this method has not produced great results is that peptide-based vaccines are incapable of sufficiently generating antigen-specific CD8+ T cells. Several systems have been studied in an attempt to improve peptide-based cancer vaccine systems including self-assembled nanoparticles, nanodiscs, and liposomes. The strong track record of liposomes in pharmaceutical products along with their high biocompatibility profile has made them a compelling system. Peptides can be loaded into liposomes through several methods such as encapsulation, or binding either covalently or non-covalently.

Researchers at the University of Buffalo are interested in a cobalt porphyrin-phospholipid (CoPoP) containing liposome due to its ability to bind peptides bearing polyhistidine-tags (his-tag). This binding is a spontaneous process that produces serum-stable antigen nanoparticles. The metal center of CoPoP is exposed to water twenty times less than metal centers of headgroup-functionalized metal-chelating lipids. Nanogram amounts of antigen delivered via CoPoP liposomes can elicit functional antibody responses when admixed with various pathogens such as malaria parasites, Lyme disease bacteria, and SARS-COV-2.

In this study, liposomes were prepared using CoPoP and the adjuvants PHAD (Avanti) and QS-21 (available from Croda-Denmark). The role of CoPop is to induce spontaneous particle formation while PHAD is a Toll-like receptor-4 agonist and QS-21 has strong binding ability with cholesterol as well as strong adjuvant effects. These liposomes were capable of inducing stable particle formation of short peptides and were effective for inducing antigen specific CD8+ T cells that inhibited tumor growth in mouse models.

This liposomal formulation works by encouraging the infiltration of antigen presenting cells (APCs) into the draining lymph nodes, increasing the efficiency of short-peptide delivery to APCs, and releasing the short-peptides for binding MHC-I. The adjuvanted CoPoP liposomes proved that they were capable of rejecting multiple types of tumor cell lines with durable immunity. Furthermore, the study showed that stable particle formation is key to this entire process. Without cobalt and its ability to form stable particles, the liposomes were incapable of inducing any kind of immune response.

If you’re interested in reading the entire scope of this study visit the publication HERE!

And, don’t forget to check out Avanti’s lipid-based adjuvant products HERE!

Image Credit: Graphical Abstract in Original Research Publication