In:
Cancer Research Communications, American Association for Cancer Research (AACR), Vol. 2, No. 8 ( 2022-08-18), p. 827-841
Kurzfassung:
Chimeric antigen receptor (CAR) T cells are efficacious in patients with B-cell malignancies, while their activity is limited in patients with solid tumors. We developed a novel heterodimeric TCR-like CAR (TCAR) designed to achieve optimal chain pairing and integration into the T-cell CD3 signaling complex. The TCAR mediated high antigen sensitivity and potent antigen-specific T-cell effector functions in short-term in vitro assays. Both persistence and functionality of TCAR T cells were augmented by provision of costimulatory signals, which improved proliferation in vitro and in vivo. Combination with a nanoparticulate RNA vaccine, developed for in vivo expansion of CAR T cells, promoted tightly controlled expansion, survival, and antitumor efficacy of TCAR T cells in vivo. Significance: A novel TCAR is tightly controlled by RNA vaccine–mediated costimulation and may provide an alternative to second-generation CARs for the treatment of solid tumors.
Materialart:
Online-Ressource
ISSN:
2767-9764
DOI:
10.1158/2767-9764.CRC-21-0154
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2022
ZDB Id:
3098144-X