Professor Luis Álvarez-Vallina, Spanish National Cancer Research Centre (CNIO)

Host: Accosiate Prof. Ken Howard

Next-generation adoptive cell therapies for cancer

T lymphocyte redirection has been addressed by two main approaches: systemic infusion of bispecific T cell engagers (TCEs), which simultaneously bind CD3 and a tumor-associated antigen (TAA), and adoptive transfer of genetically modified T cells expressing TAA-specific chimeric antigen receptors (CARs). We have developed a novel strategy based on in situ secretion of TCE antibodies by engineered T cells, termed STAb-T cells, which combines the active trafficking of adoptively transferred T cells to the tumor with polyclonal T cell recruitment by locally secreted TCEs. This approach integrates the strengths of CAR-T and TCEs, while potentially mitigating some of their limitations. Adoptive transfer of STAb-T cells has demonstrated potent antitumor activity in preclinical models of both solid and hematological malignancies. Importantly, this innovative platform is now approaching clinical translation, with the first-in-human trial of CD19-STAb expected to start soon, marking a new step in the evolution of adoptive cell therapies for cancer.