A CD19/CD22/CD3-targeting tri-specific antibody (tsAb) appears to be promising for preventing immune escape and enhancing therapeutic efficacy in B-cell acute lymphoblastic leukemia (B-ALL), according to research published in Blood.
Previous investigation of bispecific antibodies (bsAbs) targeting CD19 and CD3 has shown that these therapies are likely to be highly efficacious in B-ALL treatment. These include blinatumomab, catumaxomab, amivantamab-vmjw, and tebentafusp-tebn; the first-generation antibody, blinatumomab, in particular has drastically improved response rates among patients with relapsed or refractory disease.
There is, however, evidence that blinatumomab may have high relapse rates — of up to 50% — after 1 year. Subsequent research suggested that B-ALL cells may evolve antigen escape, which explains the high relapse rate.
Together, these previous studies suggest that a tsAb targeting CD19, CD22, and CD3 may be effective for inducing a response while preventing antigen escape. For this patient-derived xenograft model, researchers explored the efficacy of a novel tsAb, compared with that of bsAbs, in the B-ALL setting.
Analysis of the model showed that the optimized tsAb may improve induction of T-cell-specific cytotoxicity and cytokine production targeting CD19-positive or CD22-positive B-ALL cells. The tsAb also showed improved anti-tumor efficacy and prevented B-ALL immune escape compared with commonly used bsAbs, whether used as single-agents or in combination.
The authors also suggested that the tsAb may lead to long-term elimination of B-ALL cells — and potentially improve patient survival.
“Therefore, CD19/CD22/CD3…with design optimization could potentially serve as a promising therapeutic option for B-ALL patients showing blinatumomab resistance due to the heterogenicity of CD19 expression,” the authors wrote in their report.
Zhao L, Li S, Wei X, et al. A novel CD19/CD22/CD3 trispecific antibody enhances therapeutic efficacy and overcomes immune escape against B-ALL. Blood. 2022;140(16):1790-1802. doi:10.1182/blood.2022016243