Nutcracker Therapeutics’ Research Partner, the University of California, San Francisco, Presents Foundational Prostate Cancer Data at AAI 2024
May 15 2024 - 4:00PM
Business Wire
- 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