Editors' ChoiceCancer

Genie in a Bottle

See allHide authors and affiliations

Science Translational Medicine  09 Feb 2011:
Vol. 3, Issue 69, pp. 69ec18
DOI: 10.1126/scitranslmed.3002211

In The Transformed Cell, Steven Rosenberg states that his inspiration to devote his career to immunotherapy came from a melanoma patient whose tumor spontaneously regressed. Although extremely rare, such cases suggest that the body’s immune system constantly struggles to reject cancer cells as foreign and, if given a push in the right direction, might eradicate the tumor completely. This push, immunotherapy, may take many different forms. Tumor vaccines attempt to boost the body’s specific immune response against the cancer. In contrast, immune stimulants rev up the immune system nonspecifically, with the hope that cancer cells will be the first to go. Indeed, ipilimumab—an antibody that blocks CTLA-4, the “brake” on immune cells—has shown efficacy in phase III studies in melanoma. Adoptive T cell transfer is a third type of immunotherapy. In this approach, immune cells are harvested from a patient, primed to attack a tumor-specific target, and then reinjected to fight the tumor.

Steven Rosenberg’s group at the National Institutes of Health now reports the results of the adoptive transfer approach to tumor immunotherapy. The antigen they chose to target, NY-ESO-1, is a cancer/testis antigen, or CT antigen, expressed in tumors and gonads but virtually absent in normal tissues, making it immunogenic. NY-ESO-1 is expressed in 80% of synovial sarcomas and 25% of melanomas. The authors isolated tumor-infiltrating lymphocytes (TILs) from melanoma and synovial sarcoma patients and transduced them with the T cell receptor against NY-ESO-1. The cells were then reinfused into the patient. To maximize the chance of success, only patients whose tumors expressed NY-ESO-1 were studied.

The results were very encouraging. The authors observed objective responses in four of six patients with synovial cell sarcoma and five of 11 patients with melanoma. Two of the melanoma patients had complete regressions.

This is the first successful study involving the use of T cell receptor–transduced T cells in nonmelanoma cancer. It appears that Rosenberg’s instinct was correct: Understanding the immune system will allow new therapies to be developed for diseases such as melanoma and synovial sarcoma. Other tumor types may follow.

P. F. Robbins et al., Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J. Clin. Oncol. 31 January 2011 (10.1200/JCO.2010.32.2537). [Abstract]

Navigate This Article