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Novel CAR design dually targets HER2+ breast cancer and MDSCs to improve efficacy in solid tumors

Project by Polygence alum Angel

Novel CAR design dually targets HER2+ breast cancer and MDSCs to improve efficacy in solid tumors

Project's result

My research paper and original diagrams are submitted for publication in the UCI Science Journal and are published in the RARS preprint. I presented my work as a Conference Talk at the 9th Polygence Symposium of Rising Scholars 2023. In addition,

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Summary

CAR T cell therapy is a promising immunotherapy that has been approved by the FDA for use in blood cancers, but has yet to be efficacious in solid tumors due to limitations including antigen escape, on-target off-tumor effects, tumor infiltration challenges, toxicities, and the immunosuppressive tumor microenvironment. Current strategies to overcome these obstacles are ongoing and include dual target CARs, combination therapy with checkpoint blockade, local CAR administration, and targeting immunosuppressive microenvironment cells. However, additional studies are still needed to continue to improve the efficacy of CAR T. In this proposal, we first review the function of T cells in the immune system, and discuss how CAR T cell therapy enhances immune response to cancer. We also review current strategies being tested to overcome limitations in CAR T cell therapy on solid tumors. We then propose a novel CAR design that targets HER2 on breast cancer and secretes a NBD peptide that is receptive to endocytosis into MDSCs through CD73. The NBD peptide blocks the Nf-Kb signaling pathway which reduces the immunosuppressive qualities of MDSCs in the tumor microenvironment. This design requires preclinical studies to validate its efficacy and safety before being used in clinical trials. If successful, this proposal could present a novel therapeutic option for patients with HER2 positive breast cancer that would then need to be followed up with clinical studies.

Ashley

Ashley

Polygence mentor

PhD Doctor of Philosophy candidate

Subjects

Medicine, Biology, Engineering

Expertise

Designing, engineering, and testing cancer immunotherapies, biological and bioengineering research

Review of mentor

My mentor had an extensive knowledge in the exact topic I was interested in pursuing for the project. She responded quickly to my messages and was very helpful during the writing process. She also has a great way of teaching topics, in a way that allows the student to work out an answer instead of just telling them the answer. She gave lots of great tips regarding college, paper writing, and navigating the science world in general.

Angel

Angel

Student

Graduation Year

2024

Project review

I was expecting to complete a research project centered around biotechnology in cancer treatment. However, I did not expect to produce such a highly-detailed research paper or learn as much as I did about CAR T cell therapy and the process of ideating new designs in biotech!