Providing an IL-2 signal to adoptively transferred T cell therapies is expected to enhance engraftment, persistence, and functionality of infused cells ultimately leading to improved therapeutic outcomes.

Chimeric antigen receptor T cell (CAR-T) therapies have transformed the treatment of some hematological malignancies and are showing promising results in solid tumors. In the clinic, successful expansion and persistence of CAR-T cells has correlated with therapeutic outcomes, including durable complete responses and survival.Administration of IL-2 enhances CAR-T engraftment, persistence, and functionality in preclinical models. However, the clinical potential of utilizing IL-2 with CAR-T therapies is limited using current molecules due to the severe toxicity of high-dose IL-2 and the inadequate selectivity of existing engineered IL-2 variants, which expand multiple endogenous cell types in addition to transferred CAR-T cells.

We believe that a highly selective cis-targeted IL-2 fusion molecule that specifically activates only CAR-T cells, while exhibiting minimal activity on CAR-negative cells, may allow for superior efficacy and durability. This may also decrease the number of CAR-T cells required at infusion, reduce the need for preconditioning, and allow temporal control over cell activation.

In addition to the use of IL-2 fusion molecules for the support of CAR-T therapies, the modular nature of our cis-targeting platform enables the potential to: a.) deliver different, supportive cytokine signals to cell therapies, and b.) target a diverse set of cell therapies including those based on TCR-T, TILs, NK cells, and Tregs.

Cis-targeted IL-2 for cell therapies provides a means to selectively boost the transferred cells.

The problem: some patients have poor CAR-T engraftment, expansion, and functionality, and this leads to poor patient outcome

Adding cytokine support to CAR-T cells following infusion is expected to enhance engraftment, expansion, and functionality

 
 

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