The magic of small-molecule drugs during ex vivo expansion in adoptive cell therapy

• Type of Material: Article
• Authors: Hanwen Zhang, Emory University; Teenzin Passang, Emory University; Sruthi Ravindranathan, Emory University; Ramireddy Bommireddy, Emory University; Mohammad R Jajja, University of Alabama Birmingham; Lily Yang, Emory University; Periasamy Selvaraj, Emory University; Chrystal Paulos, Emory University; Edmund Waller, Emory University
• Language: English
• Date: 2023-04-21
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2023 Zhang, Passang, Ravindranathan, Bommireddy, Jajja, Yang, Selvaraj, Paulos and Waller
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fimmu.2023.1154566
• Title of Journal or Parent Work: FRONTIERS IN IMMUNOLOGY
• Volume: 14
• Start Page: 1154566
• End Page: 1154566
• Grant/Funding Information: The cancer immunotherapy research in EW’s laboratory is funded by The Katz Foundation (PI: Waller), Robert W. Woodruff Health Sciences Fund (PI: Waller), The Coulter Foundation (project 60934), NIGMS MARC program (#T34GM105550), the National Institutes of Health (NIH) fund (1R01AI145231-01A1, PI: Waller). The in vivo studies in NSG mice were also funded by the NIH grant (R01 CA202846, PI: Yang).
• Keywords: VIP; T-CELLS; ANTIVIRAL IMMUNITY; Immunology; chimeric antigen receptors (CAR); LEUKEMIA; VASOACTIVE-INTESTINAL-PEPTIDE; adoptive cell therapy (ACT); peptide-based drugs; vasoactive intestinal peptide (VIP); AKT INHIBITION; Life Sciences & Biomedicine; POLARIZATION; BONE-MARROW; protein kinase inhibitor; PI3K; ex vivo manufacturing; TYROSINE KINASE; Science & Technology; MEMORY; small-molecule drugs
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

In the past decades, advances in the use of adoptive cellular therapy to treat cancer have led to unprecedented responses in patients with relapsed/refractory or late-stage malignancies. However, cellular exhaustion and senescence limit the efficacy of FDA-approved T-cell therapies in patients with hematologic malignancies and the widespread application of this approach in treating patients with solid tumors. Investigators are addressing the current obstacles by focusing on the manufacturing process of effector T cells, including engineering approaches and ex vivo expansion strategies to regulate T-cell differentiation. Here we reviewed the current small-molecule strategies to enhance T-cell expansion, persistence, and functionality during ex vivo manufacturing. We further discussed the synergistic benefits of the dual-targeting approaches and proposed novel vasoactive intestinal peptide receptor antagonists (VIPR-ANT) peptides as emerging candidates to enhance cell-based immunotherapy.