TY - JOUR
T1 - The magic of small-molecule drugs during ex vivo expansion in adoptive cell therapy
AU - Zhang, Hanwen
AU - Passang, Tenzin
AU - Ravindranathan, Sruthi
AU - Bommireddy, Ramireddy
AU - Jajja, Mohammad Raheel
AU - Yang, Lily
AU - Selvaraj, Periasamy
AU - Paulos, Chrystal M.
AU - Waller, Edmund K.
N1 - Publisher Copyright:
Copyright © 2023 Zhang, Passang, Ravindranathan, Bommireddy, Jajja, Yang, Selvaraj, Paulos and Waller.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - adoptive cell therapy (ACT)
KW - chimeric antigen receptors (CAR)
KW - ex vivo manufacturing
KW - peptide-based drugs
KW - PI3K
KW - protein kinase inhibitor
KW - small-molecule drugs
KW - vasoactive intestinal peptide (VIP)
UR - http://www.scopus.com/inward/record.url?scp=85157992588&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85157992588&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2023.1154566
DO - 10.3389/fimmu.2023.1154566
M3 - Article
C2 - 37153607
AN - SCOPUS:85157992588
SN - 1664-3224
VL - 14
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1154566
ER -