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B7-H4 is evaluated as a breast-cancer antigen across molecular subtypes. PF-07260437, a B7-H4-targeting CD3 bispecific, induces B7-H4–dependent cytotoxicity in vitro and strong tumoricidal activity in xenograft models, often achieving complete responses. Mechanistically, it expands and activates T cells, and it enhances benefit when combined with palbociclib plus fulvestrant and anti–PD-1 in immune-competent models. Noninvasive CD8-PET imaging shows increased intratumoral CD8 T cells, and exploratory toxicology in cynomolgus monkeys supports manageable toxicity, supporting clinical testing for B7-H4–expressing solid tumors including breast cancer.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-novel-b7-h4xcd3-bispecific-t-cell-engager-pf-07260437-synergizes-with-breast-cancer-standard-of-care-and-immune-checkpoint-therapies/371626/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/a-novel-b7-h4xcd3-bispecific-t-cell-engager-pf-07260437-synergizes-with-breast-cancer-standard-of-care-and-immune-checkpoint-therapies/371626.png","ImageObject",300,407,{"name":92,"@type":93},"Bintang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",15,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is B7-H4 considered a promising antigen for breast cancer CD3 bispecific therapy?","Question",{"text":113,"@type":114},"B7-H4 is proposed as an attractive tumor-associated antigen with comprehensive coverage across breast cancer molecular subtypes. It enables targeting of tumor cells despite the difficulty of finding tumor-specific antigens for solid tumors.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What therapeutic effects does PF-07260437 produce in breast cancer models?",{"text":118,"@type":114},"PF-07260437 shows B7-H4–dependent cytotoxicity in vitro by directing cytotoxic T-cell killing to breast cancer cells. In vivo, treatment produces substantial tumoricidal activity in cell line- and patient-derived xenograft models, often resulting in complete responses.",{"name":120,"@type":111,"acceptedAnswer":121},"How does the document describe PF-07260437’s mechanism and how biomarkers are monitored clinically?",{"text":122,"@type":114},"Mechanistically, PF-07260437 increases T-cell number and activation, leading to efficient tumor killing. Clinically relevant noninvasive PET/CT using a CD8-targeting tracer demonstrates increases in intratumoral CD8 T cells, supporting CD8-PET as a potential biomarker assessment tool.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},371626,1790520731,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},962085564381,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","FIRST DISCLOSURE  \nA Novel B7-H4xCD3 Bispecific T-cell Engager (PF-07260437) Synergizes with Breast Cancer Standard of Care and Immune Checkpoint Therapies  \nKeith Abayasiriwardana1, Lei Wu1, Hanane Laklai1, Malgorzata Nocula-Lugowska2,  \nLioudmila Tchistiakova2, Jatin Narula2, Amy Jackson-Fisher1, Jonathon Golas1, My-Hanh Lam1, Veronika Grinstein1, Jung Wook Kang1, Jessica C. Kearney1, Christine Hosselet1, Erik Upeslacis1, LuAnna Lemon1, Yun Zhang3, Changhua Ji3, Bernard S. Buetow3, Martin B. Finkelstein3, Netonia Marshall1, Stephanie Bisulco1, Edward Rosfjord1, Divya Mathur1, Jennifer Athanacio1, Ashley Thomas1, Alexander Trageser1, Diane Fernandez1, Ziyue Karen Jiang4, Sripad Ram3, Edward Cabral4, Lisa Manzuk4, Kevin Maresca5, Anand Giddabasappa4, Clare Lees1,  \nAndrea T. Hooper1, Puja Sapra1, and Sudhakar Chintharlapalli1  \n|  |  | A |  | B | S |  | T | R |  | A |  | C | T |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |\n| 􀀶\u003Cbr>Immune checkpoint inhibitors have shown limited success in breast cancer, the most common and deadly cancer in women worldwide. Novel immune therapies, such as CD3-engaging bispecific antibodies, have shown clinical promise in hematologic malignancies. However, developing CD3 bispecifics for solid tumors has been challenging due to the difficulty in identifying tumor-specific antigens. B7-H4 is proposed as an attractive tumorassociated antigen for breast cancer therapeutics with comprehensive coverage regardless of breast cancer molecular subtype. We designed a B7-H4–targeting CD3 bispecific molecule, PF- 07260437, and demonstrated B7-H4–dependent pharmacology in vitro by directing cytotoxic T-cell killing to breast cancer cell lines. Treatment of cell line– and patient-derived xenograft in vivo models of human breast cancer with PF-07260437 induced substantial tumoricidal activity, often resulting in complete responses. Mechanistically, PF-07260437 increased T-cell number and activation, leading to efficient tumor killing. Additionally, combining PF-07260437 with standard of care (palbociclib plus fulvestrant) and a checkpoint inhibitor (anti–PD-1) showed combinatorial benefits in an immune-competent in vivo model. Clinically relevant noninvasive PET/CT imaging with a CD8-targeting tracer demonstrated PF-07260437–mediated increases in intratumoral CD8 T cells, highlighting the utility of CD8-PET technology to potentially assess biomarker changes in the clinic. Finally, the manageable toxicity profile of PF-07260437 was highlighted in\u003Cbr>an exploratory toxicology study in cynomolgus monkeys. These data support the clinical testing of PF-07260437 for treating B7-H4–expressing solid tumors, including breast cancer.\u003Cbr>\u003Cbr>T cell\u003Cbr>Infiltration\u003Cbr>T cell\u003Cbr>CXCL9\u003Cbr>CXCL10 MHC-indep\u003Cbr>cytolytic synapse\u003Cbr>B7-H4xCD3\u003Cbr>Activation\u003Cbr>T cell\u003Cbr>IL-2\u003Cbr>IFN-γ\u003Cbr>Cancer cell\u003Cbr>GzymB\u003Cbr>Introduction\u003Cbr>Breast cancer is the most common cancer among women, affecting 2.1 million women each year and causing the highest number of cancer-\u003Cbr>1Oncology R&D, Pfizer Worldwide Research, San Diego, California. 2Biomedicine Design, Pfizer Worldwide Research, Development and Medical, Cambridge, Massachusetts. 3Dr","cbCaifKqIoW8AkbB","https://ap.wps.com/l/cbCaifKqIoW8AkbB","pdf",31519446,17,"English","# Overview\n## Breast cancer challenge and rationale for CD3 bispecifics\n## PF-07260437 design and in vitro activity\n## In vivo efficacy and mechanisms\n## Combination with standard of care and PD-1 checkpoint inhibition\n## CD8-targeted PET/CT biomarker readout\n## Toxicology and translational implications","[{\"question\":\"Why is B7-H4 considered a promising antigen for breast cancer CD3 bispecific therapy?\",\"answer\":\"B7-H4 is proposed as an attractive tumor-associated antigen with comprehensive coverage across breast cancer molecular subtypes. It enables targeting of tumor cells despite the difficulty of finding tumor-specific antigens for solid tumors.\"},{\"question\":\"What therapeutic effects does PF-07260437 produce in breast cancer models?\",\"answer\":\"PF-07260437 shows B7-H4–dependent cytotoxicity in vitro by directing cytotoxic T-cell killing to breast cancer cells. In vivo, treatment produces substantial tumoricidal activity in cell line- and patient-derived xenograft models, often resulting in complete responses.\"},{\"question\":\"How does the document describe PF-07260437’s mechanism and how biomarkers are monitored clinically?\",\"answer\":\"Mechanistically, PF-07260437 increases T-cell number and activation, leading to efficient tumor killing. Clinically relevant noninvasive PET/CT using a CD8-targeting tracer demonstrates increases in intratumoral CD8 T cells, supporting CD8-PET as a potential biomarker assessment tool.\"}]","A Novel B7-H4xCD3 Bispecific T-cell Engager (PF-07260437) Synergizes with Breast Cancer Standard of Care and Immune Checkpoint Therapies | PDF",1790192478,43]