Kevin J Curran
Dr. Joseph Curran’s is a pediatric oncologist who specializes in bone marrow transplantation. He treats children and young adults who have hematologic malignancies such as leukemia, disorders of the bone marrow that impair the ability to make normal blood cells, and disorders of the immune system that impair the body’s ability to fight infection. His research is focused on the development of novel treatment approaches for leukemia and lymphoma that do not respond to current therapies. Specifically, he uses genetic manipulation of immune cells to recognize and kill cancer cells. This is a promising form of gene therapy and is currently being tested in clinical trials at Memorial Sloan Kettering Cancer Center for children and adults with high-risk or relapsed hematologic cancers. Through these highly innovative studies, we hope to provide a novel and successful treatment option for all patients with cancer. Contributions to Science: • Clinical application of CD19-specific chimeric antigen receptor (CAR) T cells T cells can be genetically modified to target tumor antigens through the expression of a chimeric antigen receptor (CAR). The basic design of CARs consists of two domains – the antigen binding portion (commonly composed of a single chain variable fragment (scFv) derived from a monoclonal antibody) joined to one or more intracellular signaling domains. His group and others have demonstrated promising clinical responses using T cells targeting the CD19 antigen through the expression of a chimeric antigen receptor (CAR) in patients with relapsed or refractory (R/R) B-ALL. The focus of his research is the clinical application and extension of this novel immunotherapy (CD19-specific CAR T cells) to children with R/R B-ALL. • Pre-clinical development of next generation CAR T cells termed “armored CAR” T cells To be effective following infusion, CAR T cells must expand, persist, exhibit enduring anti-tumor cytotoxicity, overcome targeted tumor antigen escape, and importantly counteract the immunosuppressive tumor microenvironment. This hostile tumor microenvironment allows for tumor evasion through the recruitment of inhibitory immune cells including regulatory CD4 T cells (Tregs), myeloid derived suppressor cells (MDSCs), tumor associated macrophages (TAMs), and the expression of immune suppressive ligands (PD-L1, PD-L2), and/or cytokines (TGFb, IL-10). Current CAR T cell technology is unlikely to overcome this hostile microenvironment which may explain the poor clinical efficacy CAR T cells have thus far demonstrated in solid malignancies. To overcome this limitation we have focused on additional genetic modification of CAR T cells (constitutive expression of CD40L or IL-12) designed to generate “armored” CAR T cells endowed the abilities to be effective within any microenvironment. • Clinical application of allo-HSCT for pediatric patients with malignant and non-malignant disorders. My clinical practice is within the pediatric bone marrow transplant service at MSKCC. Our service expertise is use of T-cell depleted/CD34+ enriched allo-HSCT for malignant and non-malignant disorders of childhood. We also have a robust cellular therapy program which includes adoptive transfer of viral specific and tumor specific immune effectors.