CD19directed

CD19-directed therapies are treatments that target the CD19 protein, a transmembrane antigen expressed on most B-lineage cells from early development through mature B cells, but typically absent on myeloid or nonhematopoietic cells. Because CD19 is broadly present on B-cell malignancies such as acute lymphoblastic leukemia and non-Hodgkin lymphoma, it has become a central target in modern B-cell–directed immunotherapy. CD19-directed approaches aim to eliminate malignant B cells while preserving other tissues, though some normal B cells are also affected.

Strategies include chimeric antigen receptor (CAR) T cells, anti-CD19 monoclonal antibodies and antibody-drug conjugates, and bispecific T-cell engagers that recruit endogenous T cells to CD19-positive cells. CAR T-cell therapies use a patient’s own T cells modified to express a CD19-targeting receptor and re-infused after lymphodepletion. Monoclonal antibodies can directly mediate cytotoxicity, or be conjugated to cytotoxic payloads. Bispecific agents, such as BiTEs, simultaneously bind CD19 on B cells and CD3 on T cells to stimulate T-cell–mediated killing.

Clinical products include CD19-directed CAR T cells such as tisagenlecleucel and axicabtagene ciloleucel, lisocabtagene maraleucel; anti-CD19 monoclonal antibodies and antibody-drug conjugates such as tafasitamab and loncastuximab tesirine; and bispecific antibodies like blinatumomab. These therapies have shown meaningful responses in certain pediatric and adult B-cell malignancies, particularly relapsed or refractory disease, but come with unique safety considerations.

Common adverse events include cytokine release syndrome and neurologic toxicities, as well as prolonged B-cell aplasia and infection risk. Monitoring, prompt management of CRS, and careful patient selection are essential. Research continues to refine indications, improve durability, and reduce toxicity for CD19-directed therapies.