In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia.

Published

Journal Article

Several recent clinical trials have successfully incorporated a costimulatory domain derived from either CD28 or 4-1BB with the original CD3ζ T cell activating domain to form second-generation chimeric antigen receptors (CARs) that can increase the responsiveness and survival of CAR-engineered T (CAR-T) cells. However, a rigorous assessment of the individual benefits of these costimulatory components relative to the in vivo performance of infused T cells in patients is still lacking. Therefore, we have designed a study that allows us to investigate and compare the impact of different costimulatory signal domains on CAR-T cells in vivo. Patients with B cell leukemia were infused with a mixture of two types of CD19-specific CAR-T cells, individually bearing CD28 (28ζ) and 4-1BB (BBζ) costimulatory signaling domains. We found that such a clinical procedure was feasible and safe. Complete remission (CR) was observed in five of seven enrolled patients, with two patients exhibiting durable CR lasting more than 15 months. The in vivo expansion pattern of 28ζ and BBζ CAR-T cells varied significantly among individual patients. These results confirm a feasible method of comparing different CAR designs within individual patients, potentially offering objective insights that may facilitate the development of optimal CAR-T cell-based immunotherapies.

Full Text

Duke Authors

Cited Authors

  • Cheng, Z; Wei, R; Ma, Q; Shi, L; He, F; Shi, Z; Jin, T; Xie, R; Wei, B; Chen, J; Fang, H; Han, X; Rohrs, JA; Bryson, P; Liu, Y; Li, Q-J; Zhu, B; Wang, P

Published Date

  • April 4, 2018

Published In

Volume / Issue

  • 26 / 4

Start / End Page

  • 976 - 985

PubMed ID

  • 29503204

Pubmed Central ID

  • 29503204

Electronic International Standard Serial Number (EISSN)

  • 1525-0024

Digital Object Identifier (DOI)

  • 10.1016/j.ymthe.2018.01.022

Language

  • eng

Conference Location

  • United States