NCI Cancer Bulletin for February 8, 2011 - National Cancer Institute: Adoptive Cell Transfer Targets New Cancer Antigen for Immunotherapy

Adoptive Cell Transfer Targets New Cancer Antigen for Immunotherapy

Results from a phase II trial suggest that an immunotherapy strategy called adoptive cell transfer (ACT) may be effective for patients with metastatic cancers, including melanoma and a tumor of the soft tissues of joints known as synovial cell sarcoma. The study, published January 31 in the Journal of Clinical Oncology, is part of an effort by researchers from NCI’s Center for Cancer Research to engineer a patient’s own white blood cells to recognize and attack his or her specific cancer.

For the treatment, Dr. Steven Rosenberg and his colleagues genetically modified the receptors on the patient’s own T cells to bind to an antigen called NY-ESO-1, which is expressed in 80 percent of synovial cell sarcomas and 15 to 30 percent of metastatic melanoma, breast, prostate, lung, and ovarian cancers. The antigen is not commonly present in normal tissues except in the testis.

From each patient who had tumors that heavily expressed the NY-ESO-1 antigen, T cells were removed. The extracted T cells were then genetically altered using a retrovirus that delivered the genetic code for building NY-ESO-1 receptors into the cells. The modified T cells were then grown in the laboratory and infused back into the patients. To prepare for the infusion of their altered T cells, the patients received chemotherapy to eliminate any other immune cells in their blood.

All 17 patients enrolled in the trial had progressive metastatic disease. The six patients with synovial cell sarcoma had been treated with multiple chemotherapies, and the 11 melanoma patients had been previously treated with interleukin-2. After ACT, five of the melanoma patients had measurable responses, and two of them had complete responses (disappearance of all signs of cancer) that were sustained at 20 and 22 months, respectively. Among the three remaining melanoma responders, one had a partial response (shrinkage of tumor size) that persisted 9 months after initial treatment. Four of the synovial cell sarcoma patients had objective partial responses, with one patient’s response lasting 18 months.

Patients in the trial experienced no toxic effects beyond those that are common with stem-cell transplantation and interleukin-2 treatment, which include neutropenia and thrombocytopenia, and the toxicities were less severe than in other trials in which ACT was used against different tumor antigens, the authors wrote.

The study “represents the first successful immunotherapy for patients with synovial cell sarcoma,” they concluded, noting that the small number of patients in the trial limits the interpretation of their results. However, the strategy against NY-ESO-1 should be explored further, they continued, because the antigen is expressed by common cancers and, thus, the treatment may be extended to many tumor types.

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NCI Cancer Bulletin for February 8, 2011 - National Cancer Institute