Development and application of an in vitro assay to assess target-independent B-cell activation by targeted TLR7 immune agonists.
- Resource Type
- Academic Journal
- Authors
- Chen Y; Merck & Co. Inc., Rahway, NJ, USA.; Zhou S; Merck & Co. Inc., Rahway, NJ, USA.; Pradhan K; Merck & Co. Inc., Rahway, NJ, USA.; Chernyak N; Merck & Co. Inc., Rahway, NJ, USA.; Kofman E; Merck & Co. Inc., Rahway, NJ, USA.; Zhang F; Merck & Co. Inc., Rahway, NJ, USA.; Kim SY; Merck & Co. Inc., Rahway, NJ, USA.; Seghezzi W; Merck & Co. Inc., Rahway, NJ, USA.; Willingham A; Merck & Co. Inc., Rahway, NJ, USA.; Seganish WM; Merck & Co. Inc., Rahway, NJ, USA.; Bhagwat B; Merck & Co. Inc., Rahway, NJ, USA.; Han JH; Merck & Co. Inc., Rahway, NJ, USA. Electronic address: jin-hwan.han@merck.com.
- Source
- Publisher: Elsevier Country of Publication: Netherlands NLM ID: 1305440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7905 (Electronic) Linking ISSN: 00221759 NLM ISO Abbreviation: J Immunol Methods Subsets: MEDLINE
- Subject
- Language
- English
Targeted immune agonist (TIA) comprising a TLR7 agonist conjugated to tumor-targeting antibodies have been shown to induce potent anti-tumor responses in various preclinical models. However, the clinical proof-of-concept of a TIA has been hampered by systemic dose-limiting immune-related toxicities, including rapid induction of anti-drug antibodies in patients. We have developed ELISPOT-based assay to measure activation of antibody-secreting cells (ASCs), intended to simulate the interaction between TIA and peripheral B cells as a tool to pre-clinically de-risk tumor target-independent peripheral B-cell activation by TIA. This method has proven to be robust and has fast turn-around time to evaluate the induction of spontaneous B-cell activation by TIA in a tumor target- and FcγR-independent manner. This novel ASC assay platform may serve as a preclinical tool to de-risk TIAs that can potentially induce immune-related adverse effects in the clinic.
(Copyright © 2023. Published by Elsevier B.V.)