Sherin Panikulam , Hannah Morgan , Michael Gutknecht , Thomas K. Villiger , Nicolas Lebesgue , Anette C. Karle
{"title":"生物治疗药物的宿主细胞蛋白介导的佐剂性和免疫原性风险。","authors":"Sherin Panikulam , Hannah Morgan , Michael Gutknecht , Thomas K. Villiger , Nicolas Lebesgue , Anette C. Karle","doi":"10.1016/j.biotechadv.2025.108575","DOIUrl":null,"url":null,"abstract":"<div><div>Host cell proteins (HCPs) are process-related impurities of biotherapeutic production that might affect product quality and/or patient safety. In a few cases, adverse events were attributed to HCPs present in the administered biotherapeutic. HCP-associated immune risks include adjuvanticity and immunogenicity with potential cross-reactivity. Based on the published data, some HCPs can act as adjuvants increasing the immunogenicity of the biotherapeutic as a bystander effect. HCPs may also induce immunogenicity against themselves, resulting in anti-HCP T cell responses and anti-HCP antibody formation. Depending on sequence similarities, these anti-HCP immune responses might theoretically be cross-reactive to the biotherapeutic or human endogenous proteins. In this review, we examine HCP-associated immune-related risks reported from non-clinical and clinical studies. We also discuss the potential and limitations of <em>in vitro</em> and <em>in silico</em> methods to evaluate the adjuvanticity and immunogenicity potential of HCPs. A risk-based assessment of the safety impact of HCPs may include the identity of the HCP and similarity to the biotherapeutic and human proteins, as well as product, treatment-, and patient-related factors.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"81 ","pages":"Article 108575"},"PeriodicalIF":12.1000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Host cell protein-mediated adjuvanticity and immunogenicity risks of biotherapeutics\",\"authors\":\"Sherin Panikulam , Hannah Morgan , Michael Gutknecht , Thomas K. Villiger , Nicolas Lebesgue , Anette C. Karle\",\"doi\":\"10.1016/j.biotechadv.2025.108575\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Host cell proteins (HCPs) are process-related impurities of biotherapeutic production that might affect product quality and/or patient safety. In a few cases, adverse events were attributed to HCPs present in the administered biotherapeutic. HCP-associated immune risks include adjuvanticity and immunogenicity with potential cross-reactivity. Based on the published data, some HCPs can act as adjuvants increasing the immunogenicity of the biotherapeutic as a bystander effect. HCPs may also induce immunogenicity against themselves, resulting in anti-HCP T cell responses and anti-HCP antibody formation. Depending on sequence similarities, these anti-HCP immune responses might theoretically be cross-reactive to the biotherapeutic or human endogenous proteins. In this review, we examine HCP-associated immune-related risks reported from non-clinical and clinical studies. We also discuss the potential and limitations of <em>in vitro</em> and <em>in silico</em> methods to evaluate the adjuvanticity and immunogenicity potential of HCPs. A risk-based assessment of the safety impact of HCPs may include the identity of the HCP and similarity to the biotherapeutic and human proteins, as well as product, treatment-, and patient-related factors.</div></div>\",\"PeriodicalId\":8946,\"journal\":{\"name\":\"Biotechnology advances\",\"volume\":\"81 \",\"pages\":\"Article 108575\"},\"PeriodicalIF\":12.1000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biotechnology advances\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0734975025000618\",\"RegionNum\":1,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biotechnology advances","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0734975025000618","RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Host cell protein-mediated adjuvanticity and immunogenicity risks of biotherapeutics
Host cell proteins (HCPs) are process-related impurities of biotherapeutic production that might affect product quality and/or patient safety. In a few cases, adverse events were attributed to HCPs present in the administered biotherapeutic. HCP-associated immune risks include adjuvanticity and immunogenicity with potential cross-reactivity. Based on the published data, some HCPs can act as adjuvants increasing the immunogenicity of the biotherapeutic as a bystander effect. HCPs may also induce immunogenicity against themselves, resulting in anti-HCP T cell responses and anti-HCP antibody formation. Depending on sequence similarities, these anti-HCP immune responses might theoretically be cross-reactive to the biotherapeutic or human endogenous proteins. In this review, we examine HCP-associated immune-related risks reported from non-clinical and clinical studies. We also discuss the potential and limitations of in vitro and in silico methods to evaluate the adjuvanticity and immunogenicity potential of HCPs. A risk-based assessment of the safety impact of HCPs may include the identity of the HCP and similarity to the biotherapeutic and human proteins, as well as product, treatment-, and patient-related factors.
期刊介绍:
Biotechnology Advances is a comprehensive review journal that covers all aspects of the multidisciplinary field of biotechnology. The journal focuses on biotechnology principles and their applications in various industries, agriculture, medicine, environmental concerns, and regulatory issues. It publishes authoritative articles that highlight current developments and future trends in the field of biotechnology. The journal invites submissions of manuscripts that are relevant and appropriate. It targets a wide audience, including scientists, engineers, students, instructors, researchers, practitioners, managers, governments, and other stakeholders in the field. Additionally, special issues are published based on selected presentations from recent relevant conferences in collaboration with the organizations hosting those conferences.