Study on the anti-leukemia effect of a novel recombinant protein CD19scFv/CD80

Abstract

B-cell acute lymphoblastic leukemia (B-ALL) is a very common hematological malignancy. Despite the curative effect of chemotherapy observed in children and adults with B-ALL, still some patients fail to respond to chemotherapy and suffer from poor prognosis. Studies have shown that the costimulatory molecule CD80 (B7.1) is expressed at low levels on ALL cells, which avoids leukemia cells being recognized and killed by cytotoxic T cells (CTLs). However, almost all B-ALL cells express CD19 antigen. Therefore, in this study, the previously constructed recombinant CD19scFv/CD80 protein, consisting of the extracellular domain of human CD80 (B7.1) and a single-chain variable fragment antibody to human CD19 antigen (CD19scFv), was used as a bridge to decorate B-ALL cells with the costimulatory molecule CD80 through the binding of CD19scFv to CD19 antigen. Using this strategy, CTLs could be activated by B-ALL cells pretreated with CD19scFv/CD80 fusion protein, and thus, they could exert their killing effect on leukemia cells. In the in vitro study, it was observed B-ALL Nalm-6 cells cocultured with the recombinant CD19scFv/CD80 fusion protein were capable of inducing donor T-cell-specific expansion, cytokine production, and cytolytic activity. In a leukemic xenograft NOD/SCID mouse model, intravenous injection of CD19scFv/CD80 fusion protein was able to significantly prolong the survival time of mice with leukemia. In conclusion, the novel CD19scFv/CD80 fusion protein could effectively modify B-ALL cells, which evade the immune surveillance, into antigen-presenting cells, which could thus activate specific immune responses, thereby implying a potential clinical value.