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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

1
Division of Cancer Medicine, Department of Cellular Therapy, and.
2
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
3
KG Jebsen Centre for B-cell Malignancies, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
4
Division of Cancer Medicine, Department of Pathology, and.
5
Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway; and.
6
KG Jebsen Centre for Cancer Immunotherapy, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.

Abstract

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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