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

Natasa Vukovic, Aina Segues Cistero, Shuyu Huang, Martin Waterfall, Alice Sijts, Dietmar Zaiss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

In the last decades, antibody-based tumor therapy has fundamentally improved the efficacy of treatment for patients with cancer. 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 antitumor effect was entirely Fc mediated as the protection was lost when an Fc-silenced mIgG2a isotype (LALA-PG mutations) was used. These data confirm mIgG2a superiority in a therapeutic tumor model.

Significance: 

Direct comparisons of different antibody isotypes of the same specificity in cancer settings are still scarce. Here, it is shown that mIgG2a has a greater effect compared with mIgG1 and mIgE in controlling tumor growth in a therapeutic setting.


Original languageEnglish
Pages (from-to)109-118
Number of pages27
JournalCancer research communications
Volume3
Issue number1
DOIs
Publication statusPublished - 6 Jan 2023

Keywords / Materials (for Non-textual outputs)

  • antibody isotype
  • tumor
  • IgG2a
  • LALA-PG
  • therapeutic setting

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