ALLO-647 + fludarabine + cyclophosphamide

This therapy is a **combination lymphodepletion regimen** consisting of ALLO-647 (a humanized anti-CD52 monoclonal antibody), fludarabine (a purine analog antimetabolite), and cyclophosphamide (an alkylating agent)[2][3][5][6]. It is administered prior to **allogeneic CAR T-cell therapy** to deplete host lymphocytes, minimize rejection of infused cells, and enhance CAR T-cell expansion and persistence[2][3][5]. - **ALLO-647** selectively binds CD52, mediating antibody-dependent cellular cytotoxicity and depletion of CD52-positive lymphocytes, thereby providing profound and durable lymphodepletion[1][3][5]. - **Fludarabine** inhibits DNA synthesis by interfering with DNA polymerase and ribonucleotide reductase in rapidly dividing cells, leading to immunosuppression. - **Cyclophosphamide** alkylates and crosslinks DNA, leading to cell death, with pronounced immunosuppressive effects. This combination is primarily **used in the preparative regimen for allogeneic CAR T-cell therapy** (such as ALLO-501, ALLO-501A, and ALLO-715) in relapsed/refractory hematologic malignancies (notably lymphomas and multiple myeloma)[2][3][5].