Cancer Communications | 2021
CD70‐targeting CAR‐T cells have potential activity against CD19‐negative B‐cell Lymphoma
Abstract
To the Editor: CD19-targeting chimeric antigen receptor T (CAR-T) cell therapy is a revolutionary immunotherapy in treating relapsed or refractory B lineage malignancies. However, relapse with CD19-negative tumor after treatment with anti-CD19 CAR-T cells has been reported in different types of B-cell lymphoid malignancies, with a percentage exceeding 10% in patients with acute lymphoblastic leukemia [1] and up to 38% in patients with non-Hodgkin lymphoma (NHL) [2]. Thus, antigen escape constitutes a significant obstacle for anti-CD19 CAR-T therapy, underscoring the need to develop CAR-T cell therapies directed to alternative antigens. CD70, the membrane-binding ligand of the CD27 (a tumor necrosis factor receptor superfamily), has been reported to be expressed on the malignant cells of diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and follicular lymphomas (FL), as well as Hodgkin’s lymphoma, Waldenström macroglobulinemia, and multiple myeloma, but rarely on normal B cells or T cells [2–4]. In addition, CD70 is also expressed in various solid tumor types, such as renal cell carcinoma and mesothelioma [3]. Recently, targeting CD70 has emerged as potential novel immunotherapeutic strategy [4–6]. Here, we report on the development of novel, second-generation CAR-T cells against CD70, a target for CAR-T cell therapy of B-cell lymphoma that has not been fully realized. CAR-T cell-based cancer immunotherapy relies on not only the specificity but also association constant of singlechain variable fragment (scFv). The scFv used in the CAR is synthesized from parent antibody by fusing their light(VL) and heavy (VH)-chain variable domains into a single chain using a peptide flexible linker. A previous study demonstrated that the CAR targeting CD79b, in which the scFv was synthesized in a light-heavy (L/H) orientation of variable domain, had superior antigen-specific effector