{"id":"04890","slug":"in-vivo-validated-anti-cd276--04890","source":{"id":"04890","dataset":"techtransfer","title":"In Vivo–Validated Anti-CD276 (B7-H3) VH-Domain/Fab Antibodies","description_":"<p>Using libraries of both engineered antibody domains (eAds) based on the IgG heavy chain variable domain (eVHd) and antibody fragments (Fabs), the University of Pittsburgh researchers developed panels of fully human single-domain eVHds and Fabs specific to CD276. </p><p><h2>Description</h2>CD276 (B7-H3) is a member of the B7 family of molecules involved in immune inhibition of T cell function and proliferation. Higher levels of CD276 expression are correlated with the development of cancer metastasis and cancer-specific mortality. CD276 is over-expressed on many solid tumor types, including prostate cancer, melanoma, squamous cell cancer of the head and neck, non-small cell lung cancer, and brain tumors; it is also found to be over-expressed in the tumor microenvironment, including on cancer stem-like cells and tumor vasculature and stroma, contributing to tumor angiogenesis and metastasis. Conversely, CD276 has restricted expression on non-cancerous tissue, making it a compelling target for anticancer therapy.</p><p><h2>Applications</h2>Immunotherapy for various solid tumors</p><p><h2>Advantages</h2>•\tThis therapy is broadly applicable to the many solid cancers in which CD276 is over-expressed\r<br>•\tExpression of CD276 on both the tumor and tumor microenvironment creates the possibility of multiple additive anti-tumor benefits\r<br>•\tPreliminary experiments indicate antibodies target domains that may also serve as potent immune checkpoint blockades\r<br>•\tMuch smaller size increases tumor penetration efficiency\r<br>•\tThese antibodies have specific epitopes, especially the ones binding to membrane-proximal domain C2 can improve their efficacy\r<br>•\tThese antibody domains and fragments to CD276 are of full human origin, suggesting less immunogenicity when used in humans</p><p><h2>Invention Readiness</h2>•\tIn vivo data. The VH and Fab binders exhibited binding to recombinant CD276 protein on a nano-molar scale and the ability to specifically target cancer cell lines that over-express CD276.</p><p><h2>IP Status</h2><a target=\"_blank\" href=\"https://patents.google.com/patent/WO2023150092A2\">https://patents.google.com/patent/WO2023150092A2</a>\r\n<a target=\"_blank\" href=\"https://patents.google.com/patent/US20240415884A1\">https://patents.google.com/patent/US20240415884A1</a></p><p><h2>Related Publication(s)</h2><p>Liu, X., Zhelev, D., Adams, C., Chen, C., Mellors, J. W., &amp; Dimitrov, D. S. (2021). Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody. Translational Oncology, 14(12), 101232. <a target=\"_blank\" href=\"https://doi.org/10.1016/j.tranon.2021.101232\">https://doi.org/10.1016/j.tranon.2021.101232</a></p><p>Majzner, R. G., Theruvath, J. L., Nellan, A., Heitzeneder, S., Cui, Y., Mount, C. W., Rietberg, S. P., Linde, M. H., Xu, P., Rota, C., Sotillo, E., Labanieh, L., Lee, D. W., Orentas, R. J., Dimitrov, D. S., Zhu, Z., Croix, B. S., Delaidelli, A., Sekunova, A., … Mackall, C. L. (2019). CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. Clinical Cancer Research, 25(8), 2560–2574. <a target=\"_blank\" href=\"https://doi.org/10.1158/1078-0432.ccr-18-0432\">https://doi.org/10.1158/1078-0432.ccr-18-0432</a></p></p>","tags":[],"file_number":"04890","collections":[],"meta_description":"Novel fully human VH-domain and Fab antibodies target CD276 (B7-H3) for versatile solid-tumor immunotherapy and enhanced penetration.","image_url":"","apriori_judge_output":"{\"scores\":{\"novelty\":4.0,\"potential_impact\":4.0,\"readiness\":3.0,\"scalability\":3.0,\"timeliness\":2.0},\"weighted_score\":3.4,\"risks\":[\"Age of data (2019) may limit novelty today\",\"TRL 3 indicates early concept with in vivo proof but not ready for clinic\",\"Potential competition in CD276 field and immunotherapy landscape\"],\"one_sentence_take\":\"Solid novelty with human-domain antibodies and in vivo validation, but current novelty/timeliness dip due to age and early TRL; moderate impact potential and scalability pending further development.\"}","lead_inventor_name":"Dimiter Dimitrov","technology_type":"Therapeutic Modality","technology_subtype":"Antibody - Bispecific","therapeutic_areas":["Oncology"],"therapeutic_indications":["Solid tumor"],"custom_tags":[],"all_tech_innovators":["Dimiter Stanchev Dimitrov","Wei Li","John W. Mellors"],"date_submitted":"2019-02-11","technology_readiness_level":"3. Initial proof of concept, in-vivo"},"highlight":{},"matched_queries":null,"score":0.0}