Chimeric antigen receptor T cells as adjuvant therapy for unresectable adenocarcinoma.
Ugur UsluTong DaCharles-Antoine AssenmacherJohn SchollerRegina M YoungJulia TchouCarl H JunePublished in: Science advances (2023)
Incomplete surgery of solid tumors is a risk factor for primary treatment failure. Here, we have investigated whether chimeric antigen receptor T cells (CARTs) could be used as an adjuvant therapy to clear residual cancer cells. We tested the feasibility of this approach in two partial resection xenograft models using mesothelin-specific CARTs. In addition, we developed a previously unexplored in vivo toxicity model to evaluate safety and effects on wound healing in immunocompetent C57BL/6 mice. We found that the local delivery of CARTs in a fibrin glue-based carrier was effective in clearing residual cancer cells following incomplete surgery. This resulted in significantly longer overall survival when compared to mice treated with surgery and CARTs without fibrin glue. On-target off-tumor toxicity was diminished, and wound healing complications were not seen in any of the mice. On the basis of these observations, a clinical trial in patients with locally advanced breast cancer is planned.
Keyphrases
- minimally invasive
- locally advanced
- coronary artery bypass
- wound healing
- clinical trial
- high fat diet induced
- squamous cell carcinoma
- rectal cancer
- surgical site infection
- oxidative stress
- neoadjuvant chemotherapy
- radiation therapy
- risk factors
- platelet rich plasma
- insulin resistance
- young adults
- phase ii study
- mass spectrometry
- skeletal muscle
- high resolution
- coronary artery disease
- smoking cessation