Panikulam, Sherin, Morgan, Hannah, Gutknecht, Michael, Villiger, Thomas K., Lebesgue, Nicolas and Karle, Anette (2025) Host cell protein-mediated adjuvanticity and immunogenicity risks of biotherapeutics. Biotechnology advances, 81. p. 108575. ISSN 1873-1899

Abstract

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.

Item Type:	Article
Keywords:	Humans Biological Products Adjuvants, Immunologic Proteins
Date Deposited:	12 Jul 2025 00:45
Last Modified:	12 Jul 2025 00:45
URI:	https://oak.novartis.com/id/eprint/55495