Panikulam, Sherin, Morgan, Hannah, Gutknecht, Michael, Karle, Anette, Rajaratnam, Atchaya, Muntwyler, Jennifer, Anderka, Oliver, Lebesgue, Nicolas and Villiger, Thomas (2025) Assessing the adjuvant potential of CHO host cell proteins using an in vitro dendritic cell assay. Biotechnology and Bioengineering. ISSN 0006-35921097-0290

Abstract

Host cell proteins (HCPs) are process-related impurities of therapeutic protein production and may affect product quality or patient safety. In clinical trials, certain HCPs (e.g., PLBL2 or CCL2) that co-purify with the therapeutic protein have been associated with immune reactions in patients. In this study, we examined the adjuvant potential of six commonly detected HCPs from CHO cells (YWHAE, S100A4, PRDX1, PLBL2, CCL2, and CLU) using an in vitro dendritic cell (DC) maturation assay. Recombinant HCPs were expressed in CHO cells to mimic manufacturing conditions. PRDX1, S100A4, and PLBL2 caused a slight increase in the expression of maturation markers on DCs, while YWHAE, CLU, and CCL2 did not. Interestingly, CLU and CCL2 reduced the DC maturation induced by rituximab. In addition, we observed that process parameters such as elution conditions during chromatographic purification can influence HCP aggregation, which in turn can mask or enhance the intrinsic adjuvant potential of an HCP. These findings not only provide initial insights into the adjuvant potential of individual HCPs but also indicate that the quantity as well as the degree of aggregation of HCPs might influence adjuvanticity.

Item Type:	Article
Keywords:	therapeutic proteins, host cell proteins, impurities, Chinese hamster ovary cells, dendritic cells, adjuvanticity
Date Deposited:	27 Feb 2025 00:45
Last Modified:	27 Feb 2025 00:45
URI:	https://oak.novartis.com/id/eprint/56263