(Sensei) Conditionally active CD28xVISTA bispecific antibodies induce myeloid-driven tumor-specific T-cell co-stimulation for improved cancer immunotherapy

Background

Tumor-specific recruitment of co-stimulatory bispecific antibodies (bsAbs) is emerging as a promising therapeutic strategy. We developed pH-selective CD28xVISTA bsAbs to act within the acidic tumor microenvironment (TME).These bsAbs are designed for selective tripartite “trans-activation” of CD28 in theTME, aiming for enhanced T-cell-mediated cancer cell killing while minimizing systemic T-cell activation and Cytokine Release Syndrome (CRS) risk.The trans-activation mechanism relies on engagement of VISTA on myeloid cells, where this immune checkpoint acts to suppress T-cell activation in the low pH environment (~pH 6) found in many tumors¹. We (Sensei) and others previously developed pH-selective monoclonal antibodies (mAbs) to inhibit this checkpoint^1,2. Here we exploit these findings to develop CD28xVISTA bsAbs for tumor-targeted CD28 agonism and T-cell co-stimulation.