{"id":42982,"date":"2025-09-10T18:47:42","date_gmt":"2025-09-10T16:47:42","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/09\/10\/ator-4066-a-bispecific-antibody-targeting-cd40-and-ceacam5-induces-strong-myeloid-and-t-cell-dependent-tumor-immunity-and-synergizes-with-pd-1-blockade\/"},"modified":"2025-09-10T18:47:42","modified_gmt":"2025-09-10T16:47:42","slug":"ator-4066-a-bispecific-antibody-targeting-cd40-and-ceacam5-induces-strong-myeloid-and-t-cell-dependent-tumor-immunity-and-synergizes-with-pd-1-blockade","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/09\/10\/ator-4066-a-bispecific-antibody-targeting-cd40-and-ceacam5-induces-strong-myeloid-and-t-cell-dependent-tumor-immunity-and-synergizes-with-pd-1-blockade\/","title":{"rendered":"ATOR-4066, a bispecific antibody targeting CD40 and CEACAM5, induces strong myeloid and T cell-dependent tumor immunity and synergizes with PD-1 blockade"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Sep 10. doi: 10.1158\/2326-6066.CIR-25-0075. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Despite recent progress within the field of immuno-oncology, immune suppression in the tumor microenvironment, defective antigen presentation, and low levels of tumor-specific T cells are key limitations of current cancer immunotherapies. CD40-targeting immunotherapies hold promises for addressing these limitations across solid tumors. Here, we describe ATOR-4066, a bispecific antibody that targets CD40 and CEACAM5 developed for immunotherapy of cancer using the Neo-X-Prime platform. ATOR-4066 showed potent CEACAM5-dependent activation in vitro with ability to activate intratumoral immune cells from patient derived material. In vivo, ATOR-4066 induced superior anti-tumor activity compared to CD40 mAb in MC38-CEA tumors and cured mice with well-established tumors with a heterogeneous CEACAM5 expression. Using RNA sequencing, flow cytometry and cytokine analysis, we show that ATOR-4066 promotes immune cell trafficking to tumors and activates both myeloid cells and T cells within the tumor microenvironment, with limited immune activation in the periphery. ATOR-4066 initially induces a T cell-independent anti-tumor response, yet a functional T cell response is critical for long-term tumor control and immunity directed to tumor antigens other than CEACAM5. Finally, we demonstrate that ATOR-4066 synergizes with PD-1 blockade in vitro. In conclusion, these data provide mechanistic evidence for the proposed mode of action and support further development of ATOR-4066 in CEACAM5 expressing cancers.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40928366\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250910124739&amp;v=2.18.0.post9+e462414\">40928366<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0075\">10.1158\/2326-6066.CIR-25-0075<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Sep 10. doi: 10.1158\/2326-6066.CIR-25-0075. Online ahead of print. ABSTRACT Despite recent progress within the field of immuno-oncology, immune suppression in the tumor microenvironment, defective antigen presentation, and low levels of tumor-specific T cells are key limitations of current cancer immunotherapies. CD40-targeting immunotherapies hold promises for addressing these limitations across solid tumors. &#8230; <a title=\"ATOR-4066, a bispecific antibody targeting CD40 and CEACAM5, induces strong myeloid and T cell-dependent tumor immunity and synergizes with PD-1 blockade\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/09\/10\/ator-4066-a-bispecific-antibody-targeting-cd40-and-ceacam5-induces-strong-myeloid-and-t-cell-dependent-tumor-immunity-and-synergizes-with-pd-1-blockade\/\" aria-label=\"Read more about ATOR-4066, a bispecific antibody targeting CD40 and CEACAM5, induces strong myeloid and T cell-dependent tumor immunity and synergizes with PD-1 blockade\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-42982","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/42982","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=42982"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/42982\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=42982"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=42982"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=42982"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}