Sarwish Rafiq, PhD1*, Tao Dao, MD/PhD2*, Cheng Liu, PhD3*, David A. Scheinberg, MD, PhD4 and Renier J Brentjens, MD, PhD5
Adoptive transfer therapy of T cells expressing chimeric antigen receptors (CAR) against tumor-associated antigens has been shown to be clinically successful in a limited set of leukemia. However, novel antigen targets for both hematological and solid malignancies are required. Most CARs described thus far are targeted against external antigens on particular cell types. We have designed and engineered the first CAR T cell against a human intracellular protein, WT1. WT1 is overexpressed in many cancers, including acute and chronic leukemias and numerous solid tumors. Our TCRm CAR, derived from the ESK1 TCRm mAb, termed WT1 28z, is reactive with the RMFPNAPYL peptide of the WT1 protein that is processed and presented on the surface of cells in the context of HLA-A*02:01. WT1 28z expressing T cells have high expression of the CAR on their surface. They are cytotoxic in standard 51Cr assays against a range of cancer cell lines, including the megakaryoblastic cell line SET2, the acute myeloid leukemia (AML) cell line AML14, the multiple myeloma cell line KARPAS, and the ovarian cancer line, OVCAR3, as compared to CAR T cells against an irrelevant antigen. The WT1 28z CAR T cells are also cytotoxic against primary AML bone marrow blasts in this assay. When co-cultured with these primary cells or cancer cell lines, the WT1 28z CAR T cells have enhanced production of proinflammatory cytokines such as IFN-g, IL-2, and GM-CSF, as compared to irrelevant CAR T cells. Importantly, WT1 28z T cells are specific for the WT1-HLA-A*02:01 complex. The cells do not show cytotoxicity against cell lines or primary cells that are not both HLA-A*02:01- positive and WT1 positive. WT1 28z T cells are currently being tested alongside irrelevant antigen CAR T cells in AML and ovarian cancer murine models in vivo to assess efficacy, with the ultimate goal of translating this novel approach into the clinical setting for both hematological and solid cancers. The data provide the proof-of-concept that CAR T cells also may be directed at intracellular antigens.
Hi Richard6000,
Last December i went to ASH meeting in San Francisco and got to know the scientific breakthrough of Car-T cell therapy in treating certain kinds of blood cancer:
Dr.Sadelain等人在ASH会议上报道指出，6名参加同一项试验的淋巴瘤患者在接受该疗法的治疗后，肿瘤症状均消失。而对于急性淋巴细胞性白血病（acute lymphoblastic leukaemia）这种更为严重的癌症而言，30名患者在经过治疗后，有27人的症状消失，而两年后他们的血液中仍然存在有CAR T细胞.
Certain Clinical trials for solid tumors are ongoing in Memorial Sloan Kettering Cancer Center (MSKCC). Here is one of their links---
http://www.mskcc.org/blog/immunotherapy-shows-promise-treating-solid-tumors-chest
You can contact Dr. Michel Sadelain's team in MSKCC to find out if they have the other clinical trials.
GOD bless you and your families with the best luck