Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma
Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma
Blog Article
Adoptive transfer of chimeric antigen receptor-transduced T cells is a promising strategy for cancer immunotherapy.The CD38 molecule, with its high expression on multiple myeloma cells, appears a suitable target for antibody therapy.Prompted by this, we used three different CD38 antibody sequences to generate second-generation retroviral CD38-chimeric antigen click here receptor constructs with which we transduced T cells from healthy donors and multiple myeloma patients.We then evaluated the preclinical efficacy and safety of the transduced T cells.Irrespective of the donor and antibody sequence, CD38-chimeric antigen receptor-transduced T cells proliferated, produced inflammatory cytokines and effectively lysed malignant cell lines and primary malignant cells from patients with acute myeloid leukemia and multi-drug resistant multiple myeloma in a cell-dose, and CD38-dependent manner, despite becoming CD38-negative during culture.
CD38-chimeric antigen receptor-transduced T cells also displayed significant anti-tumor effects in a xenotransplant model, in which multiple myeloma tumors were grown in a human bone marrow-like microenvironment.CD38-chimeric antigen receptor-transduced T cells also appeared to lyse the CD38+ fractions of CD34+ hematopoietic progenitor cells, monocytes, natural killer cells, and to a lesser extent T and B cells but did not inhibit the outgrowth of progenitor cells into various catherine lansfield ombre rainbow clouds eyelet curtains myeloid lineages and, furthermore, were effectively controllable with a caspase-9-based suicide gene.These results signify the potential importance of CD38-chimeric antigen receptor-transduced T cells as therapeutic tools for CD38+ malignancies and warrant further efforts to diminish the undesired effects of this immunotherapy using appropriate strategies.