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We recently showed that blocking Abs to mouse <jats:styled-content style=\"fixed-case\">SIRP<\/jats:styled-content>\u03b1 enhanced both the Ab\u2010dependent cellular phagocytosis (<jats:styled-content style=\"fixed-case\">ADCP<\/jats:styled-content>) activity of mouse macrophages for Burkitt's lymphoma Raji cells opsonized with an Ab to <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>20 (rituximab) in\u00a0vitro as well as the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in nonobese diabetic (<jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>)\/<jats:styled-content style=\"fixed-case\">SCID<\/jats:styled-content> mice. However, the effects of blocking Abs to human <jats:styled-content style=\"fixed-case\">SIRP<\/jats:styled-content>\u03b1 in preclinical cancer models have remained unclear given that such Abs have failed to interact with endogenous <jats:styled-content style=\"fixed-case\">SIRP<\/jats:styled-content>\u03b1 expressed on macrophages of immunodeficient mice. With the use of Rag2<jats:sup>\u2212\/\u2212<\/jats:sup>\u03b3<jats:sub>c<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup> mice harboring a transgene for human <jats:styled-content style=\"fixed-case\">SIRP<\/jats:styled-content>\u03b1 under the control of human regulatory elements (<jats:styled-content style=\"fixed-case\">hSIRP<\/jats:styled-content>\u03b1\u2010<jats:styled-content style=\"fixed-case\">DKO<\/jats:styled-content> mice), we here show that a blocking Ab to human <jats:styled-content style=\"fixed-case\">SIRP<\/jats:styled-content>\u03b1 significantly enhanced the <jats:styled-content style=\"fixed-case\">ADCP<\/jats:styled-content> activity of macrophages derived from these mice for human cancer cells. The anti\u2010human <jats:styled-content style=\"fixed-case\">SIRP<\/jats:styled-content>\u03b1 Ab also markedly enhanced the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in <jats:styled-content style=\"fixed-case\">hSIRP<\/jats:styled-content>\u03b1\u2010<jats:styled-content style=\"fixed-case\">DKO<\/jats:styled-content> mice. Our results thus suggest that the combination of Abs to human <jats:styled-content style=\"fixed-case\">SIRP<\/jats:styled-content>\u03b1 with therapeutic Abs specific for tumor antigens warrants further investigation for potential application to cancer immunotherapy. In addition, humanized mice, such as <jats:styled-content style=\"fixed-case\">hSIRP<\/jats:styled-content>\u03b1\u2010<jats:styled-content style=\"fixed-case\">DKO<\/jats:styled-content> mice, should prove useful for validation of the antitumor effects of checkpoint inhibitors before testing in clinical trials.<\/jats:p>","DOI":"10.1111\/cas.13548","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T07:32:37Z","timestamp":1519371157000},"page":"1300-1308","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Anti\u2010human <scp>SIRP<\/scp>\u03b1 antibody is a new tool for cancer immunotherapy"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9576-7030","authenticated-orcid":false,"given":"Yoji","family":"Murata","sequence":"first","affiliation":[{"name":"Division of Molecular and Cellular Signaling Department of Biochemistry and Molecular Biology 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