CAR33VH

CAR33VH is a fully human, heavy-chain variable domain-based chimeric antigen receptor (CAR) specifically designed to target the CD33 antigen, which is highly expressed on the surface of acute myeloid leukemia (AML) cells. Unlike traditional CARs utilizing single-chain variable fragments (scFvs), CAR33VH employs only a human immunoglobulin heavy chain variable (VH) domain as its antigen binding region, derived from a human VH phage display library. This design allows for potentially reduced immunogenicity and improved manufacturability. CAR33VH CAR-T cells, produced via lentiviral transduction of healthy donor-derived CD4+ and CD8+ T lymphocytes, demonstrate robust and selective cytotoxicity against CD33-positive AML cell lines both in vitro and in animal models. Upon encountering CD33-expressing targets, CAR33VH T cells secrete proinflammatory cytokines such as IFN-gamma, TNF-alpha, and IL-2. Critically, the CAR33VH approach has shown a lack of overt toxicity toward CD34+ hematopoietic stem/progenitor cells in functional assays, suggesting a favorable safety profile compared to other CD33-targeted modalities. This construct represents the first CAR utilizing a human heavy chain variable-only binder for targeting the CD33 antigen and is intended for treatment of hematologic malignancies, primarily AML[1][3][5].