A gynecologic oncology group phase II trial of two p53 peptide vaccine approaches: subcutaneous injection and intravenous pulsed dendritic cells in high recurrence risk ovarian cancer patients
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Peptide antigens have been administered by different approaches as cancer vaccine therapy, including direct injection or pulsed onto dendritic cells; however, the optimal delivery method is still debatable. In this study, we describe the immune response elicited by two vaccine approaches using the wild-type (wt) p53 vaccine.
Twenty-one HLA-A2.1 patients with stage III, IV, or recurrent ovarian cancer overexpressing the p53 protein with no evidence of disease were treated in two cohorts. Arm A received SC wt p53:264-272 peptide admixed with Montanide and GM-CSF. Arm B received wt p53:264-272 peptide-pulsed dendritic cells IV. Interleukin-2 (IL-2) was administered to both cohorts in alternative cycles.
Nine of 13 patients (69%) in arm A and 5 of 6 patients (83%) in arm B developed an immunologic response as determined by ELISPOT and tetramer assays. The vaccine caused no serious systemic side effects. IL-2 administration resulted in grade 3 and 4 toxicities in both arms and directly induced the expansion of T regulatory cells. The median overall survival was 40.8 and 29.6 months for arm A and B, respectively; the median progression-free survival was 4.2 and. 8.7 months, respectively.
We found that using either vaccination approach generates comparable specific immune responses against the p53 peptide with minimal toxicity. Accordingly, our findings suggest that the use of less demanding SC approach may be as effective. Furthermore, the use of low-dose SC IL-2 as an adjuvant might have interfered with the immune response. Therefore, it may not be needed in future trials.
Keywordsp53 IL-2 Ovarian cancer Cancer vaccine
Supported in part by the intramural research program of the National Institute of Health (NIH), National Cancer Institute, Center for Cancer Research and by of the NCI/NIH grants P01 CA109688 (TLW) and R01 DE13918 (TLW) as well as National Institute grants to the Gynecologic Oncology Group Administrative Office (CA27469) and the Gynecologic Oncology Group Statistical Office (CA37517). Dr. M. Szajnik is a postdoctoral fellow supported by the NHLBI contract HB-37-165 (TLW). The following member institutions participated in this study: Tacoma General Hospital; MD Anderson Cancer Center; Columbus Cancer Council and the Cleveland Clinic Foundation.
Conflict of interest
The authors declare that they have no conflict of interest.
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