UCSF, in Collaboration with Nutcracker Therapeutics, Unveils Groundbreaking Prostate Cancer Data at AAI 2024

Nutcracker Therapeutics, a biotechnology company focused on developing transformative RNA therapies through its proprietary technology platform, announced the presentation of key prostate cancer antigen research by its partners at the University of California, San Francisco (UCSF). The data, foundational to the development of Nutcracker’s mRNA drug candidate NTX-470, was 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.

Prostate cancer, known for its low immunogenicity and low mutation burden, offers limited druggable neoantigens, making shared tumor-associated antigens (TAAs) the primary targets for immunotherapeutic development. However, assessing the immunogenic landscape of shared prostate TAAs and understanding how antigen immunogenicity evolves with disease progression remain significant challenges. The research presented at AAI aimed to map antigen reactivity in prostate cancer to identify potential TAA combinations for treatment.

Utilizing Nutcracker’s Nutshell® technologies, the company’s scientists collaborated with UCSF researchers to create mRNAs encoding eight common and shared prostate TAAs. They employed a novel antigen recall assay to systematically study T cell immune responses in blood samples from patients with localized and metastatic prostate cancer. The study tracked cellular immune responses to shared TAAs across different cohorts and correlated these responses with treatment outcomes. Single-cell genomic analysis further characterized TAA-reactive T cell effector phenotypes and monitored TCR expansion. This comprehensive analysis offers transformative insights for developing shared antigen-directed immunotherapeutics.

“We’re proud to partner 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 innovative therapeutic strategies for prostate cancer, including NTX-470. We hope that our ongoing collaboration with UCSF will continue to illuminate unknown aspects of various cancers and aid in developing much-needed novel therapeutics.”

“There are many knowledge gaps in prostate cancer research,” said UCSF Assistant Professor of Medicine David Oh, M.D., Ph.D. “Understanding how antigen recognition changes as the cancer progresses is crucial for designing effective drugs for advanced prostate cancer. By systematically researching antigen reactivity with this programmable platform and relating it to clinical outcomes after immunotherapy, we aim to address these gaps and inspire the development of new mRNA-based immunotherapeutics for prostate cancer.”

This research, a result of a longstanding partnership between Nutcracker Therapeutics and UCSF, builds on a previous demonstration of data presented at the American Association for Cancer Research (AACR) annual meeting in 2023. Nutcracker Therapeutics has ongoing collaborations with Dr. Lawrence Fong and Dr. Oh’s labs in cancer immunotherapy.

Earlier this year, Nutcracker Therapeutics presented preclinical data at the AACR Annual Meeting for NTX-470. This multimodal mRNA therapy for prostate cancer encodes both PSMA and STEAP1 antigens and has demonstrated effective engagement of CD3 T cells with reduced off-tumor binding, potentially reducing treatment toxicity.

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