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CD229 CAR T cells (parental 2D3) is an investigational chimeric antigen receptor (CAR) T-cell therapy designed to target CD229 (also known as LY9), a cell surface receptor universally and strongly expressed on multiple myeloma plasma cells, memory B cells, and tumor-propagating cells. The therapy utilizes a CAR construct based on the fully human CD229-specific antibody clone 2D3. While the parental 2D3 CAR T cells demonstrate potent anti-tumor activity against myeloma cells, they also exhibit high affinity for healthy T cells expressing low levels of CD229, which can lead to on-target off-tumor toxicity. This specific parental version served as the baseline construct for the subsequent development of affinity-tuned, low-affinity variants intended to improve the safety profile by sparing healthy T cells. The research and development of this therapy have been led by investigators at the University of Utah and associated institutions.
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