Identification And Characterization Of The Key CART Subtypes In Anticancer Efficacy

B-cell malignancy is one of the common tumor types that shows refractory or relapse after chemotherapy and autologous stem-cell therapy.Chimeric antigen receptor T(CART)is a new autologous immunotherapy,which is genetically,modified T-lymphocytes.Antigen recognition sites of T cells are modified for the recognition of specific antigen.This therapy provides promising outcomes for hematologic malignancy.T-lymphocytes are consist of a large number of cells,which can be divided into CD4 helper T cells,and cytotoxic CD8 cells.Th1,Th2,Th17,and,Treg,etc.are the major subtypes of the CD4 T cell.Autologous T cells are a combination of cells rather than a single type and still very little is known about it.Pharmaceutical CART products are transduced within a pool of various type of cells after isolation,and that modified cells are transduced nonselectively.In addition,as a drug,one of the major limitations that main cell population for CAR antitumor effects are still not clear.In general,CD8 that acts as a cytotoxic effector cell,but Th1 subtypes in CD4 T cells can also secrete cytokine IFN-? as effector cells.IFN-? is one of the main cytokines secreted by CD8 and Th1 cells,which has an anti-tumor effect and promotes the differentiation of other immune cells.Based on the above need,I designed a research study to find out the main anti-tumor cell subsets within the mixer of T cells.These cells will be the key components of CAR-T cell therapy,which aimed to play a stronger role in future CAR-T therapy than existing therapies in the anti-tumor effect,and will guide the production and clinical application of CAR-T cells.Methods: First,In vitro CD4 and CD8 cells were isolated separately,and CD4 cells were successfully differentiated to the Th1 subtype.Then,the two groups of cells were designed to be studied individually or in combinations in different ratios for T cell function analysis,to evaluate the anti-tumor effect of each group and to analyze other functional parameters.Results: Similar to CD8 effector cells,Th1 cells showed significant antitumor effects.Conclusion: Study results figure out that,Th1 and CD8 cells are the key T cell subtypes that play a role as antitumor effector cells.Based on this discovery,we can initially narrow down the combination of CAR-T products using the combination of these two effector cells,Th1 and CD8,to increase the specific killing effect of CAR-T.