UCSF Presents Key Prostate Cancer Data at AAI 2024

Nutcracker Therapeutics, Inc., a biotechnology firm focused on the development of RNA therapies using its unique technology platform, recently highlighted research presented by the University of California, San Francisco (UCSF) at the 2024 Annual Meeting of the American Association of Immunologists (AAI) in Chicago. This research, which was presented by lead author Dr. Elena Montauti, concentrated on prostate cancer antigen studies that are instrumental in developing Nutcracker's mRNA drug candidate, NTX-470.

Prostate cancer is traditionally considered a "cold cancer" due to its low immunogenicity, which means it does not typically provoke a strong immune response. This characteristic is linked to a low mutation rate, resulting in a scarcity of neoantigens that can be targeted by drugs. Consequently, immunotherapeutic development in prostate cancer focuses on shared tumor-associated antigens (TAAs). However, identifying which shared TAAs are effective immunogenic targets across different patients and understanding how these antigens change as the disease advances remain significant challenges.

The research conducted by UCSF, in collaboration with Nutcracker Therapeutics, aimed to systematically map antigen reactivity in prostate cancer to identify potential TAA combinations for treatment. Using Nutcracker's proprietary Nutshell® technologies, scientists developed mRNAs for eight common shared prostate TAAs. They then used an innovative antigen recall assay to study T cell immune responses in blood samples from patients with both localized and metastatic prostate cancer.

The study monitored cellular immune responses to these TAAs across different patient groups and evaluated how these responses correlated with treatment outcomes after immunotherapy. Single-cell genomic analysis was utilized to detail TAA-reactive T cell effector phenotypes and track TCR expansion. This comprehensive analysis of TAA-reactive cellular responses in prostate cancer patients offers valuable insights that could significantly influence the creation of shared antigen-directed immunotherapeutics.

Dr. Samuel Deutsch, Chief Scientific Officer at Nutcracker Therapeutics, expressed pride in the partnership with UCSF, emphasizing the significance of the data presented at AAI. He highlighted the company's commitment to developing new therapeutic strategies for prostate cancer, including NTX-470, and the hope that continued collaboration with UCSF will lead to important discoveries in cancer research and the development of innovative therapeutics.

Dr. David Oh, Assistant Professor of Medicine at UCSF, noted that many gaps remain in prostate cancer research, particularly regarding how antigen recognition evolves as the disease progresses. This knowledge is crucial for designing effective treatments for advanced prostate cancer. By systematically studying antigen reactivity and correlating it with known clinical outcomes, the research aims to fill these gaps and inspire the creation of a new generation of mRNA-based immunotherapies for prostate cancer.

The research presented at AAI is part of an ongoing partnership between Nutcracker Therapeutics and UCSF, including collaborations with Dr. Lawrence Fong and Dr. David Oh’s labs in cancer immunotherapy. This latest data builds on previous findings presented by UCSF at the 2023 American Association for Cancer Research (AACR) annual meeting.

Earlier this year, Nutcracker Therapeutics showcased preclinical data on NTX-470 at the AACR Annual Meeting. This mRNA therapy targets prostate cancer by encoding PSMA and STEAP1 antigens, engaging CD3 T cells with reduced off-tumor binding, potentially lowering treatment toxicity.

Nutcracker Therapeutics combines engineering prowess with high-precision biosynthesis to develop RNA medicines efficiently. The company's advanced technology platform enables quicker and more scalable RNA therapeutic development, promising significant cost reductions and shorter development cycles compared to other RNA manufacturing methods.