Bispecific anti-CD22 T-cell engager efficiently promotes cell-mediated cytotoxicity of lymphoma, leukemia and sarcoma targets

Abstract

Abstract Immunotherapy has revolutionized cancer therapy. Two of the most recently FDA-approved immunotherapies for B-cell malignancies target CD19, in the form of a Bispecific T-Cell Engager (BiTE) antibody construct or CAR-T cells. Blinatumomab, and FDA-approved BiTE, binds to CD19 on B cells and to CD3 on T cells, mediating killer-target cell contact and T cell activation that results in effective elimination of B cells. Although CD19 is expressed by essentially all cases of B cell malignancies at clinical presentation, relapses with loss or reduction of CD19 surface expression are increasingly recognized as a cause of treatment failure. We have developed a novel BiTE consisting of humanized anti-CD22 and anti-CD3 single chain variable fragments, expressed as a single molecule and purified from tissue culture supernatant. Binding of the anti-CD22 and anti-CD3 moieties to B and T cells, respectively, was confirmed by flow cytometry. CD22-BiTE promoted cell-mediated cytotoxicity in a dose and E:T-dependent fashion, with a maximum NHL and ALL-specific killing activity of 90% in vitro. Besides canonical expression in B cells, CD22 has been reported in non-hematologic malignancies. Our analysis of TCGA data suggests CD22 is expressed in a variety of solid tumors, including sarcoma. We verified expression of CD22 message and protein in solid tumor cell lines. Accordingly, our CD22-BiTE mediated killing of HT1080 sarcoma cells in vitro. In conclusion, we report here the development of a new BiTE with killing activity against CD22+ malignancies which could represent a therapeutic option for B-cell malignancies and potentially solid tumors.