Chimeric Antigen Receptor T Cells for Lymphomas: Methods, Data, and Challenges

Antigen 16 (CD19) is an optimal target for targeted cellular therapy against all B-cell non-Hodgkin lymphomas (B-NHL)/chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and B-cell acute lymphoblastic leukemia (B-ALL). However, targeting CD19 can result in prolonged B-cell aplasia. Given the clinical experience with the anti-CD20 monoclonal antibody rituximab with temporary B-cell aplasia, severe clinical consequence has not been observed. Intravenous gamma globulin has proven to effectively supplement humoral immunity in hypogammaglobulinemic patients. Genetically engineered recombinant T-cell receptors directed against a specific tumor antigen (chimeric antigen receptors, CARs) can recognize and kill tumor cell targets. This review will focus on the clinical experience of targeting CD19 with CAR-modified T cells (19-CAR-T) for B-cell lymphomas, excluding CLL/SLL and multiple myeloma which are covered in other chapters of this book.