SAR440234

We demonstrated that the combination of CD123 T cell engager (SAR440234) and veTc boosted tumor specific T cell immunity and enhanced anti-leukemia effect in vitro...This effect was associated with an increase in cytotoxic T cell subsets and clonotypic expansion. Thus, the combination of T cell engager with adoptive T cell transfer of vaccine educated T cells is a novel approach that merits further investigation in clinical trials.

Importantly, following the dose-escalation scheme 0.1/1/3/3 µg/kg, only limited cytokine release after the 4th administration was observed, suggesting that mitigation of cytokine release can be obtained by progressive intra-monkey dose escalation. Taken together, these results indicate that CD123-CODV-TCE leads to potent and specific leukemic cancer cell killing independently of CD123 receptor density and E:T ratio, and that studies monitoring cytokine release in monkeys can be useful for future clinical development of TCEs in the setting of R/R AML.

We demonstrated that the combination of DC/AML fusion vaccine and CD123TCE led to increase in tumor specific Tc immunity, both ex-vivo and in a xenograft murine model when compared to uneducated Tc with CD123TCE or educated Tc with isotype control. Most significantly, the combination treatment was shown to eradicate AML in this model with all animals remaining AML several months post inoculation.

We demonstrated that the combination of DC/AML fusion vaccine and CD123TCE led to increase in tumor specific T cell immunity, both ex-vivo and in a xenograft murine model when compared to uneducated T cells with CD123TCE or educated T cells with isotype control molecule. Most significantly, the combination treatment was shown to eradicate AML in this model with all animals remaining disease-free several months post inoculation.