CD4-directed CAR-T cell therapy (CD4CAR) in CMML

Current understanding

CD4-directed chimeric antigen receptor T cells (CD4CAR) are engineered autologous or allogeneic T cells redirected against CD4, which is expressed on the malignant monocytic clone in chronic myelomonocytic leukemia (CMML). The mechanism leverages adoptive cellular immunotherapy to eliminate CD4+ monocytic blasts and progenitors, representing an HLA-independent, antigen-specific cytotoxic strategy distinct from hypomethylating agents or JAK inhibition. A Phase I 3+3 trial is testing this approach in relapsed/refractory CMML as a second-line therapy (evidence: early-phase clinical trial).

Evidence log

• 2026-06-24 — Chimeric Antigen Receptor T Cell Therapy Redirected to CD4 (CD4CAR)as a Second Line Treatment for Chronic Myelomonocytic Leukemia, CMML.: cross-connection with ciml-nk-cell-immunotherapy-mpn: Both are adoptive cellular immunotherapies targeting myeloid malignancy — CD4CAR uses antigen-specific engineered T cells against CD4+ monocytic CMML clones, while CIML NK leverages cytokine-primed innate effectors; together they delineate complementary T-cell vs NK-cell axes of immune-based MPN/CMML therapy. (novelty: 4)

Open questions

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