- Study used Nutcracker Therapeutics’ mRNA nanoparticles to map prostate cancer antigen reactivity across patient cohorts and clinical outcomes
- Longstanding research partnership between UCSF and Nutcracker Therapeutics underscores commitment to novel prostate cancer therapeutic development, including mRNA drug candidate NTX-470
Nutcracker Therapeutics, Inc., a biotechnology company dedicated to developing transformative RNA therapies through its proprietary technology platform, today detailed data presented by its partners at the University of California, San Francisco (UCSF) on foundational prostate cancer antigen research utilized to inform the development of its mRNA drug candidate, NTX-470. The data were presented by lead author Elena Montauti, Ph.D., from UCSF on May 4, during the 2024 Annual Meeting of the American Association of Immunologists (AAI) in Chicago.
It is well established that prostate cancer is a “cold cancer” with low immunogenicity. Its low mutation burden has resulted in very few druggable neoantigens – leaving shared tumor-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 presented at AAI aimed to map antigen reactivity in prostate cancer to inform possible combinations of TAAs that could be used as treatment for the disease.
Using its Nutshell® technologies, 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 localized 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 characterize 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.
“We’re proud to have a partnership with the talented individuals at the University of California, San Francisco,” said Chief Scientific Officer Samuel Deutsch, Ph.D. “The data presented at AAI reflects our deep commitment to new therapeutic strategies for prostate cancer, including the development of NTX-470. 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.”
“There are many knowledge gaps that currently exist in prostate cancer research,” said UCSF Assistant Professor of Medicine David Oh, M.D., Ph.D. “The means by which antigen recognition changes as the cancer progresses is still unknown – making it difficult to design and develop effective drugs for more advanced forms of prostate cancer. 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.”
The research presented at AAI was the result of a longstanding partnership between Nutcracker Therapeutics and UCSF. Currently, Nutcracker Therapeutics has partnerships with Dr. Lawrence Fong and Dr. Oh’s labs in cancer immunotherapy. This data – resulting from a collaboration with Dr. Oh – expands upon a previous demonstration of the data by UCSF at last year’s American Association for Cancer Research (AACR) annual meeting in 2023.
Previously, Nutcracker Therapeutics presented preclinical data at this year’s AACR Annual Meeting for NTX-470. This multimodal mRNA therapy for prostate cancer encodes both PSMA and STEAP1 antigens, and was shown to effectively engage CD3 T cells with reduced off-tumor binding, which may result in diminished treatment toxicity.
About Nutcracker Therapeutics, Inc.
Nutcracker Therapeutics, Inc. is an RNA therapeutics company that has combined the power of advanced engineering with high-precision biosynthesis to deploy a complete RNA platform that encompasses the design, delivery, and manufacturing of RNA medicines. Armed with this high-tech advantage, the company has initiated multiple therapeutic programs with the support of clinical investigators at leading institutions. Nutcracker Therapeutics’ technology platform has the potential to significantly reduce costs and cycle times for RNA therapeutic development, with dramatic advantages in speed and capacity scaling over other RNA manufacturing approaches.
For more information, visit www.nutcrackerx.com.
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Maggie Williard
HDMZ
Nutcrackerpr@hdmz.com
