Adoptive T-Cell Immunotherapy: One Step Forward

Mojtaba Akhtari, MD

Cell therapy is not a new therapeutic modality anymore. Allogeneic hematopoietic stem cell transplantation is a good example of this treatment strategy, which can successfully overcome chemotherapy-resistant hematological malignancies through graft-vs-leukemia effect.

Adoptive T-cell immunotherapy is another form of cell therapy through transfusing ex vivo expanded T cells. It is an attractive treatment strategy, which uses effector T lymphocytes (CD8+ and CD4+) and regulatory T (Treg) cells, and it has been studied as a therapeutic modality for viral infections and various types of solid and liquid cancers in recent decades.

Despite all the achievements and advances in our understandings of adoptive T-cell therapy, it has not gone beyond early stages of feasibility and safety, and it has been far from real-time clinical application. However, a recent case report using the above mentioned strategy in a patient with refractory chronic lymphocytic leukemia (CLL) should be interpreted as one more step forward towards the availability of this type of therapy for cancer patients. The study, by Porter et al, was published last August in the New England Journal of Medicine.[1]

Porter and colleagues redirected autologous T cells with chimeric antigen receptor with specificity for B lymphocyte antigen CD19; and they also added costimulatory signaling domains to the chimeric antigen receptor. They used CD137 and CD3-zeta domains. This new strategy is quite attractive since it has the potentials to overcome problems such as short-lived T-cell expansion and transient antitumor effect, which are the major limiting factors for using adoptive T-cell immunotherapy.

Interestingly the patient developed delayed tumor lysis syndrome 22 days after receiving autologous T cells; and chimeric antigen receptor-positive T cells were detectable 6 months after treatment; those observations are indicative of prolonged and sustained effector function of the transfused chimeric-receptor T cells. The patient also developed B cell lymphopenia and hypogammaglobulinemia, which are expected.

This case report highlights the promising potentials of adoptive T-cell immunotherapy by redirecting them, through chimeric antigen receptors, as a novel and effective therapeutic modality for cancer.

References:

1. Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011; 36: 725–733.