Tumor-derived Cell-membrane Coated NanoVaccine (TCC-NV) as personalized neoantigen immunotherapy to enhance efficacy of TNBC treatments

About This Grant

PROJECT ABSTRACT This proposal seeks to overcome critical limitations in personalized therapeutic strategies for triple-negative breast cancer (TNBC), an aggressive subtype marked by poor prognosis. We propose developing personalized cancer treatment, designed to stimulate antigen-presenting cells and induce robust, antigen-specific T cell responses against TNBC cells. We develop cost-effective Tumor-derived Cell-membrane Coated NanoVaccine (TCC-NV) armed with adjuvants, that bypass limitation of resource-intensive neoantigen prediction, prioritization, and validation process. Our proposed TCC-NV integrated with radiotherapy (RT) addresses the challenge of low mutation burden in TNBC that often limits personalized neoantigen-based treatments. This multifaceted approach leverages immune-competent mouse models that closely mimic human TNBC, focusing on the innate and adaptive immune system's role in anti-tumor responses. Specific Aims are: 1) Evaluate antitumor activity of TCC-NV in TNBC tumor models. 2) Investigate radiation impact on increasing neoepitope presentation and determine whether immune checkpoint inhibitors (ICI) therapy can synergize with TCC-NV to eradicate TNBC tumors. The TCC-NV platform's production simplicity facilitates clinical translation and increases the potential for future clinical success in personalized treatment of primary and metastatic TNBC. This mechanistic study is related to the mission of the NCI as it aims to contribute to closing the knowledge gap in understanding the role and function of neoantigen-based cancer vaccine therapy and to provide survival benefits for TNBC patients who urgently require more effective treatment strategies beyond traditional chemotherapy. Dr. Yazdimamaghani’ s career goals are to integrate research from nanomedicine, radiation biology, oncology, and immunology to launch a robust and successful research program by receiving a tenure track faculty position. By leading multidisciplinary research to push the boundaries of personalized cancer immunotherapy and mentoring the next generation of scientists in immunoengineering, he aims to build a successful career as an assistant professor. His vision is to establish a highly collaborative research team focused on unraveling the complex dynamics of immune cell-biomaterial-tissue interactions within the TME, driving the development of innovative immunotherapeutic strategies for effective disease treatment. The NCI Transition Career Development Award is a vital cornerstone for successfully launching his independent research laboratory. It provides essential support for developing expertise in grant writing, effective research management, communication skills, and fostering constructive collaborations. Closely collaborating with Dr. Charles Perou, a world-renowned expert in breast cancer genomics and molecular subtypes, and Dr. Benjamin Vincent, a specialist in cancer immunogenomics, ensures comprehensive expertise, support, and access to state-of-the-art resources for the proposed experiments. Both collaborators are affiliated with the UNC School of Medicine and the UNC Lineberger Comprehensive Cancer Center, fostering an ideal environment for advancing this research.