Kenneth Anderson, MD
Director, LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Dana-Farber
Kraft Family Professor of Medicine, Harvard Medical School
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BCMA-Specific Immunotherapy Approaches to Multiple Myeloma
Project Overview
- Despite availability of CAR T-cell therapy, new immunotherapy strategies are needed for treatment of multiple myeloma (MM).
- Dana-Farber has developed a portfolio of immunotherapy alternatives to CAR T-cell therapy that target B Cell maturation antigen (BMCA) for the treatment of MM.
- This technology is available to commercial, development, and/or licensing partners.
Technology
CAR T-cell therapies have been developed for MM that display high response rates in relapsed/refractory patients. These therapies achieve high success by targeting B Cell maturation antigen (BCMA), which is a receptor that is only expressed on myeloma and plasma cells but is not present in healthy tissue.
Despite their success, CAR T-cell therapies are not broadly applicable in a clinical setting. CAR T-cell treatment requires lymphodepletive chemotherapy and is associated with dangerous side effects, like cytokine release syndrome. For these reasons, CAR T-cell therapy must be administered in specialized treatment centers, limiting access for majority of patients. Additionally, cytotoxic T lymphocytes are susceptible to “exhaustion” (i.e., unable to proliferate) during the ex vivo expansion phase, limiting the overall possible immune response of the therapy. Novel immunotherapeutic approaches to MM treatment are still needed.
Dana-Farber offers a portfolio of immunotherapy alternatives to CAR T-cell therapy for the treatment of MM. These technologies target BMCA, so they retain the specificity that made CAR T‑cell therapy successful. However, they overcome the limitations of CAR T-cells by introducing alternative preparation methods for immunotherapies.
Underlying these technologies is a peptide-based immunotherapeutic approach, targeting BCMA by generating antigen-specific CD8+ cytotoxic T lymphocytes (CTLs) with effective and long-lasting immunity against MM cells. The technology identifies novel immunogenic native and heteroclitic HLAA2-specific BCMA peptides capable of eliciting MM-specific responses with highly effective anti-tumor activities.
Induced pluripotent stem cells (iPSC) are reprogrammed to differentiate into CTLs with specificity to the BMCA receptor. These CTLs demonstrate greater proliferative capacity than ex vivo expanded CAR T-cells and are therefore resistant to the CTL exhaustion that renders CAR T-cells ineffective. Furthermore, the iPSC-derived CTL demonstrated greater cytotoxicity to MM in in vitro studies compared to CAR T-cell derived CTL.
Further details:
Lin, Liang, et al. Preclinical evaluation of CD8+ anti-BCMA mRNA CAR T-cells for treatment of multiple myeloma. Leukemia 35.3 (2021): 752-763.
Team Members: Kenneth Anderson, MD, Nikhil Munshi, MD, Jooeun Bae, PhD
Applications
- Treatment of Multiple Myeloma
- Treatment of pre-cancerous blood disorders (e.g., smoldering multiple myeloma or monoclonal gammopathy of undetermined significance)
- Treatment of Waldenstrom’s macroglobulinemia
Opportunities
The Dana-Farber Cancer Institute is seeking commercial, development, and/or licensing partners for this technology.
Team Members
Nikhil Munshi, MD
Director of Basic and Correlative Science, Jerome Lipper Multiple Myeloma Center, Dana-Farber
Kraft Family Chair and Professor of Medicine, Harvard Medical School
Jooeun Bae, PhD
Lead Investigator, Dana-Farber and Harvard Medical School
