Bio
Sujith Joseph is a Senior Scientist at the Center for Cell and Gene Therapy, Baylor College of Medicine (BCM), Houston, Texas. He received his PhD in Life Sciences from Central Drug Research Institute, India and completed postdoctoral training in Immunology and Vaccinology at National Institutes of Health, USA. His research interests include developing gene-modified T-cells for solid tumors as well as developing vaccines against infectious diseases. Currently, along with the translational research team of Drs. Nabil Ahmed and Meenakshi Hegde at BCM, he leads pre-clinical development of novel Chimeric Antigen Receptor (CAR) T-cells against solid tumor targets and immune profiling of patients responding to CAR T-cells in clinical trials to improve therapeutic outcomes in children and young adults.

Abstract

Immune Profiling Reveals Antigen Spreading after HER2 CAR T-cell Therapy in Sarcoma

Chimeric Antigen Receptor (CAR) T cells combine the specificity of an antibody with the functionality of T cells. A phase I study testing CAR T cells targeting human epidermal growth factor receptor 2 (HER2) is currently ongoing for patients with advanced HER2 positive sarcoma (NCT00902044). In this trial, multiple infusions of HER2 CAR T-cells in a child with refractory alveolar rhabdomyosarcoma (RMS) metastatic to the bone marrow, induced a complete response (CR) that was durable. The objective clinical benefit observed in the patient was investigated to identify involvement of broader host immune responses that may have contributed to tumor elimination. Following the CAR T-cell infusion, we observed remodeling of the T-cell receptor (TCR) repertoire in the peripheral blood and bone marrow metastatic sites. Additionally, evaluation of the CAR T-cell induced endogenous humoral immune response identified autoantibody generation against proteins involved in oncogenic signaling pathways in rhabdomyosarcoma.