{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:26:38Z","timestamp":1761513998101,"version":"3.38.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recent advances in immuno-oncology have shown that the immune system can be activated to induce long-term, durable antitumor responses. For immuno-oncology drug development, immune activation is often explored using rat Abs in immunocompetent mouse models. Although these models can be used to show efficacy, antidrug immune responses to experimental protein-based therapeutics can arise. Immunogenicity of surrogate Abs may therefore represent an important obstacle to the evaluation of the antitumor efficacy of immunomodulator Abs in syngeneic models. A recent publication has shown that anti-glucocorticoid\u2013induced TNFR family\u2013related protein agonistic Ab DTA-1 (rat or murinized IgG2a) can induce the development of anaphylaxis in C57BL\/6 mice upon repeated i.p. dosing because of an anti-idiotypic anti-drug Ab immune response. This study was undertaken to address the impact of the immunogenicity derived from the Fc and variable domains. To this end, chimerized (rat V domains\/mouse constant regions) and murinized (95% mouse sequence) DTA-1\u2013based surrogate Abs with a murine IgG2c H chain isotype were created. Chimerization and murinization of DTA-1 did not affect receptor binding and glucocorticoid-induced TNFR family\u2013related protein\u2013induced T cell agonistic properties. Similar in vivo antitumor efficacy and intratumoral CD8+\/regulatory T cells were also observed. Finally, treatment of C57BL\/6 mice with the chimerized and murinized DTA-1 Abs on a C57BL\/6-matched IgG2c isotype resulted in reduced development and severity of anaphylaxis as measured by decline of body temperature, behavioral effects, serum IL-4, IgE, and anti-drug Ab levels. These results suggest that careful murinization and selection of a strain-matched H chain isotype are critical to generate ideal surrogate Abs for testing immuno-oncology mechanisms in vivo.<\/jats:p>","DOI":"10.4049\/jimmunol.1601512","type":"journal-article","created":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T00:30:31Z","timestamp":1493253031000},"page":"4502-4512","source":"Crossref","is-referenced-by-count":3,"title":["Murinization and H Chain Isotype Matching of the Anti-GITR Antibody DTA-1 Reduces Immunogenicity-Mediated Anaphylaxis in C57BL\/6 Mice"],"prefix":"10.1093","volume":"198","author":[{"given":"Nicole A","family":"Belmar","sequence":"first","affiliation":[{"name":"Oncology Biologics Department, AbbVie Biotherapeutics Inc. , Redwood City, CA 94063"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah W","family":"Chan","sequence":"additional","affiliation":[{"name":"Oncology Biologics Department, AbbVie Biotherapeutics Inc. , Redwood City, CA 94063"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melvin I","family":"Fox","sequence":"additional","affiliation":[{"name":"Oncology Biologics Department, AbbVie Biotherapeutics Inc. , Redwood City, CA 94063"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josue A","family":"Samayoa","sequence":"additional","affiliation":[{"name":"Oncology Biologics Department, AbbVie Biotherapeutics Inc. , Redwood City, CA 94063"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia M","family":"Stickler","sequence":"additional","affiliation":[{"name":"Oncology Biologics Department, AbbVie Biotherapeutics Inc. , Redwood City, CA 94063"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ninian N","family":"Tran","sequence":"additional","affiliation":[{"name":"Oncology Biologics Department, AbbVie Biotherapeutics Inc. , Redwood City, CA 94063"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiko","family":"Akamatsu","sequence":"additional","affiliation":[{"name":"Oncology Biologics Department, AbbVie Biotherapeutics Inc. , Redwood City, CA 94063"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Hollenbaugh","sequence":"additional","affiliation":[{"name":"Oncology Biologics Department, AbbVie Biotherapeutics Inc. , Redwood City, CA 94063"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3817-1203","authenticated-orcid":false,"given":"Fiona A","family":"Harding","sequence":"additional","affiliation":[{"name":"Oncology Biologics Department, AbbVie Biotherapeutics Inc. , Redwood City, CA 94063"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamsell M","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Oncology Biologics Department, AbbVie Biotherapeutics Inc. , Redwood City, CA 94063"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,6,1]]},"reference":[{"key":"2025030615150688300_r1","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nature10673","article-title":"Cancer immunotherapy comes of age","volume":"480","author":"Mellman","year":"2011","journal-title":"Nature"},{"key":"2025030615150688300_r2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1126\/science.aaa8172","article-title":"The future of immune checkpoint therapy","volume":"348","author":"Sharma","year":"2015","journal-title":"Science"},{"key":"2025030615150688300_r3","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","article-title":"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer","volume":"366","author":"Topalian","year":"2012","journal-title":"N. 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