靶向 CD22 和 CD3 的新型双特异性 T 细胞衔接器（BiTE）具有体内外活性，并在急性淋巴细胞白血病（ALL）肿瘤模型中与 blinatumomab 协同作用

Immunotherapy has revolutionized cancer therapy. Two recently FDA-approved immunotherapies for B-cell malignancies target CD19, in the form of a Bispecific T-Cell Engager (BiTE) antibody construct or chimeric antigen receptor T (CAR-T) cells.

Blinatumomab, an FDA-approved BiTE, binds to CD19 on B cells and to CD3 on T cells, mediating effector-target cell contact and T-cell activation that results in effective elimination of target B cells. Although CD19 is expressed by essentially all B-cell malignancies at clinical presentation, relapses with loss or reduction in CD19 surface expression are increasingly recognized as a cause of treatment failure.

Therefore, there is a clear need to develop therapeutics for alternate targets.

We have developed a novel BiTE consisting of humanized anti-CD22 and anti-CD3 single chain variable fragments. Target binding of the anti-CD22 and anti-CD3 moieties was confirmed by flow cytometry. CD22-BiTE promoted in vitro cell-mediated cytotoxicity in a dose and effector: target (E:T)-dependent fashion.

Additionally, in an established acute lymphoblastic leukemia (ALL) xenograft mouse model, CD22-BiTE demonstrated tumor growth inhibition, comparable to blinatumomab.

Further, the combination of blinatumomab and CD22-BiTE yielded increased efficacy in vivo when compared to the single agents.

In conclusion, we report here the development of a new BiTE with cytotoxic activity against CD22 + cells which could represent an alternate or complementary therapeutic option for B-cell malignancies.