PHASE I STUDY TO EVALUATE THE SAFETY OF CELLULAR ADOPTIVE IMMUNOTHERAPY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Patients with advanced ovarian cancer generally respond to surgery and chemotherapy, but most will relapse with chemo-resistant disease. Treatment of early recurrences and residual disease represents a unique opportunity to evaluate the use of immune-based therapies. We have developed methods to isolate antigen-specific T-cells from the peripheral blood of patients for clinical trials of adoptive immunotherapy. A major limitation of previous adoptive immunotherapy trials in melanoma patients was the short survival of infused CD8+ lymphocytes in the absence of CD4+ helper function. CD4+ lymphocytes may be required for CD8+ survival and function, and alone may mediate an anti-tumor effect. Study Questions: We propose to examine the safety and duration of persistence of adoptively transferred tumor-reactive NY-ESO-1-specific CD4+ T-cell clones in patients with advanced ovarian cancer. A secondary objective is to assess the antitumor efficacy of the CD4+ T-cells. Study Design and Population: Patients with Stage III or IV disease between ages 18-75 with a KPS>=70 will be offered screening for tumor expression of NY-ESO-1 and the relevant HLA types. Patients will undergo leukapheresis and antigen specific T cell clones will be generated in the lab. If a patient relapses or has residual disease, they will be offered a single CD4+ T cell infusion. Outcomes: The maximum tolerated dose will be determined by dose escalation and stopping rules defined in the protocol. To determine T cell clone persistence, blood samples will be analyzed by quantitative real-time PCR. Antitumor response will be assessed by radiographic imaging and serum CA-125.