Anti-SEMA4D antibody regulates immune-cell infiltration and inhibits growth of Tubo.A5 orthotopic mammary carcinoma. Anti-SEMA4D antibody regulates immune-cell.

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Anti-SEMA4D antibody regulates immune-cell infiltration and inhibits growth of Tubo.A5 orthotopic mammary carcinoma. Anti-SEMA4D antibody regulates immune-cell infiltration and inhibits growth of Tubo.A5 orthotopic mammary carcinoma. Tubo.A5 cells were implanted s.c. into mammary fat pad of Balb/c mice. A, weekly treatment with anti-SEMA4D/MAb67 or isotype-matched control antibodies (50 mg/kg i.p., starting 6 dpi, n = 14) resulted in maximal TGD of 133%**** and 86% CR****. B, tumor growth in individual mice is shown. At 90 days after implant (dotted line), 13 tumor-free mice, along with 6 naïve mice, were implanted with viable Tubo.A5 cells on the contralateral side. 0/12 mice developed tumors in MAb67-treated regressor mice, while 6 of 6 naïve mice developed tumors. Tumor-bearing animals were treated as above and tumors were harvested on day 39, before tumor rejection. At the time of harvest, the average tumor volumes were 528 and 323 mm3 for the control and MAb67 treatment groups, respectively, resulting in 38% tumor growth inhibition (P = 0.0015). C, frequency of F4/80+/CD11c+ APCs was assessed by IHC on tumor sections. D and E, TILs were enriched using Lympholyte-M from dissociated Tubo.A5 tumors. Pooled samples were analyzed for T cells and MDSCs by FACS, and levels of MCP-1 by CBA analysis. Tubo.A5 tumors treated with MAb67 exhibit increased T-cell infiltration, with decreased levels of immunosuppressive MDSCs and MCP-1. Elizabeth E. Evans et al. Cancer Immunol Res 2015;3:689-701 ©2015 by American Association for Cancer Research