In a therapeutic setting, mouse IgG2a isotype is superior to mIgG1 or mIgE in controlling tumor growth

In the last decades, antibody based tumor therapy has fundamentally improved the efficacy of treatment for cancer patients. Currently, almost all tumor-antigen targeting antibodies approved for clinical application are of IgG1 Fc-isotype. Similarly, the mouse homolog mIgG2a is the most commonly used in tumor mouse models. However, in mice the efficacy of antibody based tumor therapy is largely restricted to a prophylactic application. Direct isotype comparison studies in mice in a therapeutic setting are scarce. In this study, we assessed the efficacy of mouse tumor-targeting antibodies of different isotypes in a therapeutic setting using a highly systematic approach. To this end, we engineered and expressed antibodies of the same specificity but different isotypes, targeting the artificial tumor antigen CD90.1 / Thy1.1 expressed by B16 melanoma cells. Our experiments revealed that in a therapeutic setting mIgG2a was superior to both mIgE and mIgG1 in controlling tumor growth. Furthermore, the observed mIgG2a anti-tumor effect was entirely Fc-mediated as the protection was lost when antibodies with a Fc silenced mIgG2a isotype (LALA-PG mutations) was used. These data confirm mIgG2a superiority in a therapeutic tumour model.