Supplementary Figures 1 through 3 from Antibody-Mediated Phosphatidylserine Blockade Enhances the Antitumor Responses to CTLA-4 and PD-1 Antibodies in Melanoma

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posted on 2023-04-03, 23:11 authored by Bruce D. Freimark, Jian Gong, Dan Ye, Michael J. Gray, Van Nguyen, Shen Yin, Michaela M.S. Hatch, Christopher C.W. Hughes, Alan J. Schroit, Jeff T. Hutchins, Rolf A. Brekken, Xianming Huang

Supplemental figure 1. Binding of mch1N11 antibody to PS in the presence of mouse beta 2-glycoprotein I. Supplemental Figure 2. Quantitative immunohistochemistry of K1735 tumors following combination therapy of PS-targeting antibody and anti-PD-1 antibody. Supplemental figure 3. Enhanced Production of IFNgamma by Splenocytes of Combination Therapy-treated Animals is Dependent on Presence of Tumor.

Funding

Peregrine Pharmaceuticals Inc.

History

ARTICLE ABSTRACT

In tumor-bearing animals, the membrane phospholipid phosphatidylserine (PS) suppresses immune responses, suggesting that PS signaling could counteract the antitumor effect of antibody-driven immune checkpoint blockade. Here, we show that treating melanoma-bearing mice with a PS-targeting antibody enhances the antitumor activity of downstream checkpoint inhibition. Combining PS-targeting antibodies with CTLA-4 or PD-1 blockade resulted in significantly greater inhibition of tumor growth than did single-agent therapy. Moreover, combination therapy enhanced CD4+ and CD8+ tumor-infiltrating lymphocyte numbers; elevated the fraction of cells expressing the proinflammatory cytokines IL2, IFNγ, and TNFα; and increased the ratio of CD8 T cells to myeloid-derived suppressor cells and regulatory T cells in tumors. Similar changes in immune cell profiles were observed in splenocytes. Taken together, these data show that antibody-mediated PS blockade enhances the antitumor efficacy of immune checkpoint inhibition. Cancer Immunol Res; 4(6); 531–40. ©2016 AACR.