{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:30:34Z","timestamp":1786447834025,"version":"build-2736575974"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Monoclonal antibodies (mAbs) have transformed the treatment of cancer and immune disorders, but their single-target nature limits efficacy against heterogeneous tumors and mutating pathogens. Recombinant polyclonal antibodies (RPABs)\u2014defined as mixtures of typically 2\u201325 defined mAbs produced as a single drug substance from one mixed master cell bank\u2014were proposed to combine the epitope breadth of polyclonal antibodies with the manufacturing consistency of mAbs. This review critically analyzes the four RPABs candidates that have entered clinical trials to date (Sym001, Sym004, Sym013, and Sym015), all developed by Symphogen using its proprietary Sympress\u2122 platform. We identify seven interrelated barriers that collectively explain why no RPABs product has yet received regulatory approval: modest efficacy restricted to biomarker-selected subgroups, significant toxicity, pharmacokinetic mismatch among components, instability of mixed cell banks, lack of standardized quality control methods, regulatory uncertainty, and commercial deprioritization after acquisition. Critically, we distinguish between scientific failure (Sym013, discontinued after early termination of its Phase I trial due to tolerability concerns and pharmacokinetic mismatches) and strategic discontinuation (Sym001 and Sym015, which showed clinical signals but were deprioritized for commercial reasons). All clinical and manufacturing data analyzed in this review are derived exclusively from Symphogen\u2019s proprietary Sympress\u2122 platform, as no other RPABs candidate from independent developers has entered clinical trials. We conclude that without independent validation of manufacturing consistency, pharmacokinetic-based component ratio design, and a dedicated regulatory pathway, RPABs face an uncertain future. Recommendations for future development are provided.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1849298","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:42:36Z","timestamp":1786444956000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and clinical application of recombinant polyclonal antibodies"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiaqi","family":"Jin","sequence":"first","affiliation":[{"name":"College of Biotechnology, Campus of Jiangsu University of Science and Technology, Zhenjiang","place":["Jiangsu, China"]},{"name":"State Key Laboratory of National Security Specially Needed Medicines","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojiang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of National Security Specially Needed Medicines","place":["Beijing, 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