Chimeric antigen receptors for the adoptive T cell therapy of hematologic malignancies

Int J Hematol. 2014 Apr;99(4):361-71. doi: 10.1007/s12185-013-1479-5. Epub 2013 Dec 6.


The genetic modification of autologous T cells with chimeric antigen receptors (CARs) represents a breakthrough for gene engineering as a cancer therapy for hematologic malignancies. By targeting the CD19 antigen, we have demonstrated robust and rapid anti-leukemia activity in patients with heavily pre-treated and chemotherapy-refractory B cell acute lymphoblastic leukemia (B-ALL). We demonstrated rapid induction of deep molecular remissions in adults, which has been recently confirmed in a case report involving a child with B-ALL. In contrast to the results when treating B-ALL, outcomes have been more modest in patients with chronic lymphocytic leukemia (CLL) or other non-hodgkin's lymphoma (NHL). We review the clinical trial experience targeting B-ALL and CLL and speculate on the possible reasons for the different outcomes and propose potential optimization to CAR T cell therapy when targeting CLL or other indolent NHL. Lastly, we discuss the pre-clinical development and potential for clinical translation for using CAR T cells against multiple myeloma and acute myeloid leukemia. We highlight the potential risks and benefits by targeting these poor outcome hematologic malignancies.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, CD19 / immunology
  • Antigens, CD19 / metabolism
  • Genetic Therapy
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology*
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunotherapy, Adoptive*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / therapy
  • Multiple Myeloma / genetics
  • Multiple Myeloma / immunology
  • Multiple Myeloma / therapy
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Receptors, Antigen / genetics
  • Receptors, Antigen / immunology*
  • Receptors, Antigen / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Recombinant Fusion Proteins / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • Antigens, CD19
  • Receptors, Antigen
  • Recombinant Fusion Proteins