CD19 CAR T cell adoptive therapy has resulted in dramatic clinical responses which have been associated with in vivo expansion and long term persistence of the engineered T cells. Some patients have experienced tumor lysis syn drome and prolonged now depletion of B cells is common. A clinical protocol that uses the autologous T cells expressing CAR specific for the folate receptor alpha is being developed by University of Pennsylva nia investigators in cooperation with the National Can cer Institute Cancer Immunotherapy Trial Network. FRa is over expressed on the surface of epithelial malignancies including ovarian, breast, renal, colorectal, lung, and other solid cancers, but its expression is limited on normal tissue.
The protocol involves adoptive cell therapy with genetically engi neered autologous T cells given to patients with ovarian cancer following lymphodepletion alone or followed by the administration of recombinant IL 7 and was rationa lized by the established role for IL 7 in maintaining Inhibitors,Modulators,Libraries T cell memory and homeostasis, as well as initial observa tions by Powell et al. that transferred tumor antigen specific T cells dramatically up regulate the IL 7 recep tor immediately after infusion. Reprogramming cells The reprogramming of adult cells in order to produce more primitive cells or stem cells is becoming an impor tant part of cellular therapy of cancer. Adult cells can be reprogrammed to produce induced pluripotent stem cells which have properties similar to embryonic stem cells. Investigators are now working to reprogram T cells to produce stem like T cells that are more effective in adoptive cell therapy.
Induced pluripotent stem cells Methods to reprogram stem cells have improved greatly since Yamanaka first demonstrated that the transfer of 4 transcription factors, Oct4, Klf4, Sox2 and cMyc, into fibroblasts Inhibitors,Modulators,Libraries can produce IPSCs. IPSCs differ in some respects from embryonic stem cells but these dif ferences can be reduced by removing the transcription factor used for reprogramming. One Inhibitors,Modulators,Libraries method involves reprogramming using a single excisable lentivral vector containing all 4 transcription factors which allows for highly efficient reprogramming Inhibitors,Modulators,Libraries and IPSCs free of exo genous transgenes using from fresh and store blood Inhibitors,Modulators,Libraries samples. Traditional culture of IPSCs involves the growth of cells on feeder cell layers or extracellular matrix derived from animals and the use of media sup plemented with animal serum.
Methods are being devel oped to produce and culture IPSC using xenogenic free materials and reagents which will improve the safety of these products. Companies are developing platforms for high throughput IPSC generation. These platforms also allow for cell maintenance and characterization. Reprogramming T cells Several studies have found that T cell phenotype affects their either effectiveness for adoptive cell therapy.