ABSTRACT
Recent years,chimeric antigen receptor T-cell(CAR-T)therapy has made great strides in enabling better treatment of malig-nant tumors,especially hematological tumors,as well as increasing the research prospects of potential solid tumor therapies.Conse-quently,CAR-T therapy is expected to become the selected treatment for patients with relapsed and refractory tumors.Immune check-point inhibitors also have certain curative effects in the treatment of cancers,such as liver cancer,refractory Hodgkin's lymphoma,and other malignant tumors,which brings promise to patients with advanced cancer.However,both treatments have different degrees of limitations.Recent clinical trials suggest that combined immune checkpoint inhibitors impair the immunosuppressive effects of the tu-mor microenvironment,increase the efficacy of CAR-T therapy,and prolong the survival.This article will review the research progress on the combination of CAR-T immunotherapy and immune checkpoint inhibitors in malignancies theray.
ABSTRACT
Objective@#To investigate the specific cytotoxicities of the second and third generations of chimeric antigen receptor (CAR) -engineered T cells (CAR-T) on different lymphomas.@*Methods@#CAR-Ts were prepared by lentivirus packaging and infection of T cells. CCK-8, ELISA and Lactate dehydrogenase cytotoxicity assay were applied to detect the proliferation capacity, the secretion level of inflammatory factor and the specific cytotoxicity. Flow cytometry assay showed the specific cytotoxicity and residual level of CAR-T in lymphomas of treated mice.@*Results@#The results showed that the third generation CAR-T had greater capacity of the specific cytotoxicity and proliferation capacity than of the second generation CAR-T. But there was no prominent change of the secretion level of inflammatory factor. The specific cytotoxicity of the second generation CAR-T on highly aggressive lymphomas Raji was more prominent than in inert EHEB, but also could achieve satisfactory effect. The tumor burden in the mice injected with Raji was lower than in the mice injected with EHEB from nude mice experiment. But the residual level of CAR-T in the EHEB-injected mice was higher than in the Raji-injected ones. So the second generation CAR-T was more suitable for the treatment of indolent lymphoma.@*Conclusion@#The second generation CD19 CAR-T could treat aggressive lymphoma in a relatively short period, while the second generation CD19 CAR-T need a longer time in vivo to achieve satisfactory curative effect on the noble lymphoma.