Bispecific antibodies for immune cell retargeting against cancer

Following the approval of the T cell engaging bispecific antibody blinatumomab, immune cell retargeting with bispecific or multispecific antibodies has emerged as a promising cancer immunotherapy strategy, offering alternative mechanisms compared to immune checkpoint blockade. As we gain more understanding of the complex tumor microenvironment, rules and design principles have started to take shape on how to best harness the immune system to achieve optimal anti-tumor activities.In the present review, we aim to summarize the most recent advances and challenges in using bispecific antibodies for immune cell retargeting and to provide insights into various aspects of antibody engineering. Discussed herein are studies that highlight the importance of considering antibody engineering parameters, such as binding epitope, affinity, valency, and geometry to maximize the potency and mitigate the toxicity of T cell engagers. Beyond T cell engaging bispecifics, other bispecifics designed to recruit the innate immune system are also covered.Diverse and innovative molecular designs of bispecific/multispecific antibodies have the potential to enhance the efficacy and safety of immune cell retargeting for the treatment of cancer. Whether or not clinical data support these different hypotheses, especially in solid tumor settings, remains to be seen.