Study reveals insights into antigen reactivity in prostate cancer

Cancer research in lab

Researchers from the University of California, San Francisco (UCSF) shared new data on foundational prostate cancer antigen research at the 2024 Annual Meeting of the American Association of Immunologists (AAI) in Chicago.

Prostate cancer’s low mutation burden has resulted in very few druggable neoantigens – leaving shared tumour-associated antigens (TAAs) as the primary targets for immunotherapeutic development.

However, the larger landscape of which shared prostate TAAs are immunogenic targets is challenging to assess and has not been systemically studied across patients. Further, it is unknown how antigen immunogenicity evolves as the disease progresses.

The research aimed to map antigen reactivity in prostate cancer to inform possible combinations of TAAs that could be used as treatment for the disease.

The research will be utilised to inform the development of Nutcracker Therapeutics’ mRNA drug candidate, NTX-470.

Novel immunotherapies for prostate cancer

Nutcracker Therapeutics’ scientists worked with UCSF researchers to create mRNAs encoding eight common and shared prostate TAAs, and employed a novel antigen recall assay to systematically study T cell immune responses in blood samples of patients with localised and metastatic prostate cancer.

Cellular immune responses to shared TAAs were tracked across cohorts and correlated with treatment and disease outcomes after immunotherapy. Single-cell genomic analysis was used to characterise TAA-reactive T cell effector phenotypes and to track TCR expansion.

Together, this in-depth analysis of TAA-reactive cellular responses in prostate cancer patients provides potentially transformative insights for the development of shared antigen-directed immunotherapeutics.

Samuel Deutsch, Chief Scientific Officer of Nutcracker Therapeutics, said: “We’re hopeful that with our continued work with our partners at UCSF, we can continue conducting research that sheds a light on the unknowns of different cancers, and informs the development of much-needed novel therapeutics – whether by Nutcracker Therapeutics or others in the field.” Read the DDW interview with Samuel Deutsch.

“There are many knowledge gaps that currently exist in prostate cancer research,” said UCSF Assistant Professor of Medicine, David Oh. “By systematically researching antigen reactivity using this programmable platform, and relating this to known clinical outcomes after immunotherapy, we aim to lay the groundwork to address these existing knowledge gaps, with the hopes of inspiring the development of a new generation of mRNA-based immunotherapeutics for prostate cancer.”

Diana Spencer, Senior Digital Content Editor, DDW

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