Fcgレセプターは抗PD-1/PD-L1抗体の抗腫瘍活性を調節する

文献

Rony Dahan, Emanuela Sega, John Engelhardt, Mark Selby, Alan J. Korman, and Jeffrey V. Ravetch, FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 published in Cancer Cell.

サマリー

Tumor cells are known to evade the immune system via expression of PD-L1 with antibody blockade of the PD-1/PD-L1 axis resulting in therapeutic responses across tumor types. The interaction of the fragment crystallizable (Fc) domain of therapeutic antibodies with Fcg receptors (FcgRs) has been shown to play a role in therapeutic activity. In this study, a group of researchers led by Dr. Jeffrey Ravetch at Rockefeller University investigated the impact of Fc and FcgRs interactions in the efficacy of PD-1 and PD-L1 antibodies.

Type I FcgRs are present as either activating receptors or inhibitory receptors with effector responses being mediated by the ratio of activating-to-inhibitory receptor binding. Increasing activator binding of the Fc portion of therapeutic IgGs can increase their therapeutic response. To test the role of FcgR binding in response to PD-1 and PD-L1 antibodies, the researchers created chimeric antibodies joining the Fab domain of existing rat antibodies and mouse Fc domains with different binding affinities for FcgRs. They discovered that the ability of PD-L1 antibodies to produce an anti-tumor response is dependent on Fc engagement with FcgRs. The chimeric antibody with preferential binding to inactivating FcgRs and a null variant lacking ability to bind FcgRs were less able to thwart tumor growth in mouse models than a chimeric antibody with high activating receptor binding. In contrast to this finding, the anti-PD-1 chimeric antibodies were not dependent on FcgR binding. In fact, these antibodies exhibited stronger anti-tumor activity in the absence of activating FcgR binding capabilities.

The group next turned their attention to the mechanism of the activating FcgR requirement for PD-L1 antibody activity by utilizing a mutant mouse lacking all activating FcgRs but retaining expression of the inhibitory FcgRIIb. Compared to wild type mice, this mutant showed less response to PD-L1 antibodies, again underscoring the importance of activating FcgRs in PD-L1 antibody response. By studying the splenic and tumor-infiltrating myeloid populations of these mice, the researchers were able to show that myeloid subsets within the tumor microenvironment were altered by activating FcgR interactions and activating FcgRs play a role in mediating depletion of immunosuppressive cells. Additional experiments showed activating FcgRs reduce the efficacy anti-PD-1 antibodies via reduction of CD8+ cells in the tumor microenvironment.

In this study, researchers demonstrated that PD-L1 and PD-1 antibodies have distinct FcgR requirements for optimal activity. This research highlights the value of considering Fc domain interactions in research and development of therapeutic antibodies.

文献で使用された抗体

カタログ番号 製品名 クローン名
BP0146 InVivoPlus anti-mouse PD-1 (CD279) RMP1-14
BP0101 InVivoPlus anti-mouse PD-L1 (B7-H1) 10F.9G2™
BP0083 InVivoPlus mouse IgG1 isotype control, unknown specificity MOPC-21
BP0085 InVivoPlus mouse IgG2a isotype control, unknown specificity C1.18.4
BP0090 InVivoPlus rat IgG2b isotype control, anti-keyhole limpet hemocyanin LTF-2
BP0089 InVivoPlus rat IgG2a isotype control, anti-trinitrophenol 2A3

関連するBio X Cell社製リコンビナント抗体

カタログ番号 製品名 クローン名
CP162 RecombiMAb anti-mouse PD-1 (CD279) RMP1-14-CP162
CP157 RecombiMAb anti-mouse PD-1 (CD279) RMP1-14-CP157
CP002 RecombiMAb anti-mouse PD-1 (CD279) (D265A) RMP1-14-CP002
CP168 RecombiMAb anti-mouse PD-L1 (B7-H1) 10F.9G2™-CP168
CP001 RecombiMAb anti-mouse PD-L1 (B7-H1) (D265A) 10F.9G2™-CP001

関連ページ

Bio X Cell社 – 抗PD-1抗体の選び方
Bio X Cell社 – 免疫チェックポイント関連商品

Bio X Cell社 紹介ページへ戻る

各商品の価格のお問合せ、商品仕様書のご依頼、その他のお問い合わせは下記までお願いします。
【商品取扱元】株式会社 東京未来スタイル
info@tokyofuturestyle.com
TEL:029-851-9222 FAX:029-851-9220

一覧へ戻る場合はこちらをクリックして下さい。