Chimeric Antigen Receptor-Modified T Cells and T Cell-Engaging Bispecific Antibodies: Different Tools for the Same...

Both chimeric antigen receptor (CAR) T cells and T cell-engaging antibodies (BiAb) have been approved for the treatment of hematological malignancies. However, despite targeting the same antigen, they represent very different classes of therapeutics, each with its distinct advantages and drawbacks. In this review, we compare BiAb and CAR T cells with regard to their mechanism of action, manufacturing, and clinical application. In addition, we present novel strategies to overcome limitations of either approach and to combine the best of both worlds.

By now there are multiple approaches combining the advantages of BiAb and CAR T cells. A major area of research is the application of both formats for solid tumor entities. This includes improving the infiltration of T cells into the tumor, counteracting immunosuppression in the tumor microenvironment, targeting antigen heterogeneity, and limiting off-tumor on-target effects. BiAb come with the major advantage of being an off-the-shelf product and are more controllable because of their half-life. They have also been reported to induce less frequent and less severe adverse events. CAR T cells in turn demonstrate superior response rates, have the potential for long-term persistence, and can be additionally genetically modified to overcome some of their limitations, e.g., to make them more controllable.