Scientists from Trinity College Dublin have made an important breakthrough that offers promise for developing new immune therapies for cancer. They have discovered that a vaccine adjuvant - or "booster" - called C100 promotes potent anti-tumour immunity when it is injected directly into tumours in an animal model.

The scientists found that C100, derived from chitin - one of the most common building materials in nature, and which gives strength to the exoskeletons of crustaceans, insects, and the cell walls of fungi - is highly effective at stimulating a key sensing and signalling molecule which regulates anti-tumour immune responses.

Their highly promising work has been published today in the leading international journal Cell Reports Medicine.

Ed Lavelle, Professor of Vaccine Immunology in Trinity's School of Biochemistry and Immunology and based in the Trinity Biomedical Sciences Institute, is the senior author of the research. He said: "In situvaccines are a form of cancer immunotherapy which aim to transition the tumour itself into a vaccine. For this to work well, you need to use an adjuvant, 'or vaccine booster' to kickstart anti-tumour immunity.

"As you'd expect there are numerous hurdles to clear even when you have isolated a potential target. One such target is a sensing and signalling molecule known as 'STING', but until now adjuvants targeting it have failed to clear some key hurdles in the cellular environment."

While further work is required, the newly published study characterises C100’s mechanism of action and offers significant hope that it might clear some of these hurdles and ignite the immune response scientists and clinicians are hoping for.

The scientists now know how C100 exclusively activates one arm of a specific signalling pathway (cGAS-STING) without causing inflammatory responses that could interfere with anti-tumour immunity and which may otherwise prevent therapies achieving clinical success.

Additionally, the team discovered that injecting C100 led to synergistic therapeutic effects with a "checkpoint blocker", which can release the brakes on the immune response.

"This highlights the potential that C100 has for combination approaches with other cancer immunotherapies, which could help to improve response rates," said Joanna Turley, co-first author of the research article.

"Our work offers detailed new insights into how C100 works, which is critical as you need a functional blueprint to be able to design a therapeutic battle plan, and we now have significant hope that C100 can be developed into a highly effective adjuvant for use in cancer immune therapies in the future."

Joint first author, Ross Ward, added: "In situ vaccination has the advantage of not relying on identifying highly variable vaccine neoantigens, but requires potent and targeted adjuvants that can induce protective anti-tumour immunity. Our research indicates that C100 has substantial potential in this setting."

Turley JL, Ward RW, Huete-Carrasco J, Muñoz-Wolf N, Roche K, Jin L, Bowie A, Andersson M, Lavelle EC.
Intratumoral delivery of the chitin-derived C100 adjuvant promotes robust STING, IFNAR, and CD8+ T cell-dependent anti-tumor immunity.
Cell Rep Med. 2024 May 2:101560. doi: 10.1016/j.xcrm.2024.101560