Consistent, long-term PD1 blockade using a syngeneic, engineered anti-PD1 antibody

Antibodies targeting immune checkpoint proteins are becoming an important branch of anti-cancer therapeutics. In order to further our understanding of the mechanisms underlying immunotherapy, new research tools are required, as widely used research reagents are not benefitting from the same protein engineering advances therapeutics can harness. The majority of antibodies used in vivo in mice are of rat or hamster origin, and are therefore immunogenic, leading to adverse immunological reactions and gradual loss of activity.

In this study, we compared short-term and long-term efficacy of the original rat IgG2a version of the anti-mouse PD1 antibody RMP1-14 against a recombinantly engineered version of RMP1-14 featuring an Fc Silent™ syngeneic mouse IgG2a Fc domain in a non-immunogenic HEP1-6 liver cancer model. Syngeneic mouse IgG2a Fc Silent™ antibodies showed better dose efficacy and more homogenous treatment responses, reducing tumor size in mouse models more effectively than the traditional rat monoclonal antibody.

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