Chapter Three - Applications of trimerbodies in cancer immunotherapy

ElsevierVolume 369, 2022, Pages 71-87International Review of Cell and Molecular BiologyAbstract

Trimerbodies, with their unique structural and functional properties, are the basis of a new generation of therapeutic antibodies, which due to their small size and plasticity are ideal for the generation of novel biological protein drugs with multiple competitive advantages over conventional full-length monoclonal antibodies. Since their emergence, trimerbodies have been used in preclinical cancer diagnosis and therapy. Trimerbodies are highly adaptable molecules, as they allow target-specific modulation of T cell–mediated anti-tumor immunity to enhance preexisting responses or to generate de novo immune responses. In fact, a tumor-specific humanized 4-1BB-agonistic trimerbody has shown a rather impressive safety and efficacy profile in preclinical studies making it a realistic option for clinical development. Moreover, thanks to the avidity effect they are endowed with considerable therapeutic potential as carriers to deliver cytotoxic payloads to tumors. In addition, molecular imaging studies could benefit from some intermediate-sized trivalent trimerbodies as promising candidates for targeted therapy and tumor imaging.

Keywords

Trimerbodies

Bispecific antibodies

Next-generation antibodies

Cancer immunotherapy

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