Some advanced cancers can now be successfully treated by synthetic immune cells that are more powerful and longer-lasting than any found in the body.
NATURE REVIEWS CANCER | REVIEW
Andrew D. Fesnak, Carl H. June & Bruce L. Levine
The immune system evolved to distinguish non-self from self to protect the organism. As cancer is derived from our own cells, immune responses to dysregulated cell growth present a unique challenge. This is compounded by mechanisms of immune evasion and immunosuppression that develop in the tumour microenvironment. The modern genetic toolbox enables the adoptive transfer of engineered T cells to create enhanced anticancer immune functions where natural cancer-specific immune responses have failed. Genetically engineered T cells, so-called 'living drugs', represent a new paradigm in anticancer therapy. Recent clinical trials using T cells engineered to express chimeric antigen receptors (CARs) or engineered T cell receptors (TCRs) have produced stunning results in patients with relapsed or refractory haematological malignancies. In this Review we describe some of the most recent and promising advances in engineered T cell therapy with a particular emphasis on what the next generation of T cell therapy is likely to entail.
ORIGINAL ARTICLE | BRIEF REPORT
Alfred L. Garfall, M.D., Marcela V. Maus, M.D., Ph.D., Wei-Ting Hwang, Ph.D., Simon F. Lacey, Ph.D., Yolanda D. Mahnke, Ph.D., J. Joseph Melenhorst, Ph.D., Zhaohui Zheng, M.S., Dan T. Vogl, M.D., Adam D. Cohen, M.D., Brendan M. Weiss, M.D., Karen Dengel, R.N., B.S.N., Naseem D.S. Kerr, M.P.H., Adam Bagg, M.D., Bruce L. Levine, Ph.D., Carl H. June, M.D., and Edward A. Stadtmauer, M.D.
A patient with refractory multiple myeloma received an infusion of CTL019 cells, a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, after myeloablative chemotherapy (melphalan, 140 mg per square meter of body-surface area) and autologous stem-cell transplantation. Four years earlier, autologous transplantation with a higher melphalan dose (200 mg per square meter) had induced only a partial, transient response. Autologous transplantation followed by treatment with CTL019 cells led to a complete response with no evidence of progression and no measurable serum or urine monoclonal protein at the most recent evaluation, 12 months after treatment. This response was achieved despite the absence of CD19 expression in 99.95% of the patient’s neoplastic plasma cells. (Funded by Novartis and others; ClinicalTrials.gov number, NCT02135406.)