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Blood Adv. 2019 Apr 23;3(8):1230-1243. doi: 10.1182/bloodadvances.2018029678.

Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma.

Author information

Division of Cancer Medicine, Department of Cellular Therapy, and.
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
KG Jebsen Centre for B-cell Malignancies, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
Division of Cancer Medicine, Department of Pathology, and.
Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway; and.
KG Jebsen Centre for Cancer Immunotherapy, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.


T cells modified to express chimeric antigen receptor (CAR) targeting CD19 (CD19CAR) have produced remarkable clinical responses in patients with relapsed/refractory B-cell acute lymphoblastic leukemia. CD19CAR T-cell therapy has also demonstrated prominent effects in B-cell non-Hodgkin lymphoma (B-NHL) patients. However, a subset of patients who relapse after CD19CAR T-cell therapy have outgrowth of CD19- tumor cells. Hence, development of alternative CARs targeting other B-cell markers represents an unmet medical need for B-cell acute lymphoblastic leukemia and B-NHL. Here, we confirmed previous data by showing that, overall, B-NHL has high expression of CD37. A second-generation CD37CAR was designed, and its efficacy in T cells was compared with that of CD19CAR. In vitro assessment of cytotoxicity and T-cell function upon coculture of the CAR T cells with different target B-cell lymphoma cell lines demonstrated comparable efficacy between the 2 CARs. In an aggressive B-cell lymphoma xenograft model, CD37CAR T cells were as potent as CD19CAR T cells in controlling tumor growth. In a second xenograft model, using U2932 lymphoma cells containing a CD19- subpopulation, CD37CAR T cells efficiently controlled tumor growth and prolonged survival, whereas CD19CAR T cells had limited effect. We further show that, unlike CD19CAR, CD37CAR was not sensitive to antigen masking. Finally, CD37CAR reactivity was restricted to B-lineage cells. Collectively, our results demonstrated that CD37CAR T cells also can effectively eradicate B-cell lymphoma tumors when CD19 antigen expression is lost and support further clinical testing for patients with relapsed/refractory B-NHL.

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