Posted: Monday, May 1, 2023
The potential benefits of chimeric antigen receptor (CAR) T cells targeting CD133 in tumor eradication have been well documented. Yet, these benefits have been limited because of the negative impact of the immunosuppressive tumor microenvironment on antitumor functioning, according to a presentation given at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract 4105/24). Efforts aimed at mitigating the role of the tumor microenvironment have revealed a lentiviral vector that self-secretes anti–PD-L1 signals, which may prove to be a therapeutic alternative warranting additional analysis, suggested Thanich Sangsuwannukul, PhD, of the Siriraj Center of Research Excellence for Cancer Immunotherapy, Bangkok, Thailand, and colleagues.
Two lentiviral vectors containing either an anti-CD133 single-chain variable fragment (scFv), CD3ζ, and 4-1BB co-stimulatory molecule (133CAR) or an anti-CD133 scFv, CD3ζ, and 4-1BB co-stimulatory molecule in tandem with an anti-PD-L1 scFV (133CARsL) were created. CD133-specific CAR T cells (133CART and 133CARTsL) were created through the transduction of the lentiviruses. Cholangiocarcinoma cells that co-expressed CD133 and PD-L1 were cultured with 133CART and 133CARTsL for either a short or extended duration.
The study authors did not identify any significant differences in antitumor effects between cells cultured in 133CART and 133CARTsL for a short period. However, when cultured for an extended period, decreased expression of PD-L1 was identified in 133CARTsL. Moreover, 133CARTsL also exemplified improved cytotoxic function against cells co-expressing CD133 and PD-L1. A similar trend in gene expression and cytotoxic function was observed after a tumor rechallenge.
Disclosure: The study authors reported no conflicts of interest.