Harald Kolmar

Immune-Cell Engagement in Tumour Therapy: From Bispecific to Multispecific Antibodies

Therapeutic strategies for cancer treatment have led to the rise of bispecific and multispecific antibodies in recent years that are now gaining importance due to their power of binding multiple tumor-associated antigens (TAA) simultaneously and/or redirecting immune cells to the tumor microenvironment to enhance anti-tumor activities and combining different mechanisms of action. The design and generation of multifunctional antibodies is often hampered by the structural complexity of these molecules that require correct synthesis and assembly of different heavy and light chains thereby limiting their developability. We recently established a strategy for the generation of antibodies, where the light chain and the heavy chain binds different target proteins simultaneously. Furthermore, we established a procedure for expeditious generation of so-called common light chain antibodies where target binding is mainly mediated by the variable domain of the antibody heavy chain. By combining these formats and strategies we were able to generate tetrafunctional antibodies with prescribed binding characteristics aimed at optimizing TAA binding, immune cell engagement and simultaneous mitigating unwanted side effects such as overshooting cytokine release.