Dual-Action Vaccine Shown to Attack, Shrink Solid Tumors

Breast tumor microenvironment. (NIH, Flickr. https://flic.kr/p/GA1wRk)

27 Oct. 2022. Research with lab animals shows an experimental cancer vaccine generates immune-system cells that infiltrate solid tumors and reduce the tumor’s protective environment. Results of the study conducted by the Vaccine Research Center at National Institutes of Health, testing a technology developed by Vaccitech plc in Oxford, U.K., appeared yesterday in the journal Cell (paid subscription required).

Vaccitech is a six year-old spin-off biopharmaceutical business from the Jenner Institute, a vaccine research center at University of Oxford developing protective and therapeutic vaccines that stimulate the immune system against infectious diseases and cancer.  Among the company’s technologies is a process called SnapVax that programs and assembles multiple antigens and immune-system regulators in nanoscale particles that target specific populations of T-cells in the immune system. Vaccitech says it’s developing therapies for cancer and autoimmune disorders with SnapVax, where nanoparticles with components link together into therapeutic chains.

For cancer therapies, Vaccitech says SnapVax vaccines stimulate T-cells, white blood cells in the in the immune system to produce proteins that kill cancer cells. In earlier preclinical studies, also conducted with NIH’s Vaccine Research Center and published in Jan. 2020 and Nov. 2020, vaccines made with antigen peptides using the SnapVax process generated CD8 and CD8+ T-cells in the adaptive immune system that produced cancer-killing proteins.

Promotes tumor shrinkage

The new study seeks to extend the SnapVax process to not only cancer-killing proteins but also to reduce the supportive microenvironment that protects tumors from immune-system responses. The team led by Vaccine Research Center immunologist Robert Seder tested vaccines with tumor antigen peptides, as in the earlier studies, to generate cancer-killing proteins from CD8+ T-cells in the adaptive immune system. Added to the peptides with SnapVax are Toll-like receptor agonist molecules to invoke the innate immune system. The researchers gave lab mice induced with solid-tumor cancers the SnapVax vaccine, as either an intravenous infusion or injection under the skin.

Results show both vaccine delivery methods produced cancer-killing proteins from CD 8+ T-cells in the mice, but only the intravenous method also generates an innate immune response against the microenvironment, promoting shrinkage of the tumors. The authors say after the SnapVax intravenous infusions, mice also show a reduction in a characteristic gene signature for tumor microenvironments. In addition, part of that tumor microenvironment or TME gene signature is also found in white blood cells in humans with cancer, and associated with less favorable outcomes.

Andrew Ishizuka, a co-author of the paper and senior V.P. for translational research at Vaccitech, says in a company statement, “It is broadly recognized that T-cells and checkpoint inhibitors that unleash their potential are essential, but this study highlights the critical importance of engaging the innate immune system to reverse suppressor populations in the TME that can otherwise inhibit T-cells.” The company applies this SnapVax technique to its therapy candidate for cancers from the human papilloma virus, code-named VTP-1100, and expects to request authorization for clinical trials in the first half of 2023.

Ishizuka and co-author Geoffrey Lynn were chief scientist and CEO respectively of Avidea Technologies, a spin-off enterprise from Johns Hopkins University. Lynn co-founded Avidea Technologies in 2016 to commercialize research on polymer-drug conjugates, from his doctoral studies in biomedical engineering at Oxford and with the NIH Vaccine Research Center. In Dec. 2021, Vaccitech acquired Avidea Technologies for $40 million.

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