A randomized phase II p53 vaccine trial comparing subcutaneous direct administration with intravenous peptide-pulsed dendritic cells in high risk ovarian cancer patients
| Autor: | M. S. Achtar, Seth M. Steinberg, Samir N. Khleif, Carmen Visus, Eva Wieckowski, Theresa L. Whiteside, Malgorzata Czystowska, Jay A. Berzofsky, V. E. Herrin |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 25:3011-3011 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2007.25.18_suppl.3011 |
| Popis: | 3011 Background: 50% of ovarian cancers carry a p53 mutation, most of which can lead to overexpression of the protein, providing a unique target for vaccine therapy. Preclinical data shows cytotoxic T-lymphocytes can be generated against wild-type peptide and can lyse tumor cells overexpressing p53. There are many methods of antigen delivery for cancer vaccines and very few comparative studies have been conducted to determine the best of these. Here we report findings for this completed study comparing two methods of vaccination. Methods: Eligible patients had Stage III, IV, or recurrent ovarian cancer and were clinically NED at study entry. Elevated CA-125 was allowed. HLA-A2.1 and overexpression of p53 were required. A wild-type epitope (264–272) with high HLA-A2.1 affinity was utilized for vaccination. Two techniques were randomly compared: subcutaneous (SQ) peptide admixed with ISA-51 and GM-CSF adjuvants or peptide-pulsed dendritic cells given intravenously (IV). Both arms received 6 million IU/m2 IL-2 SQ for ten days beginning with cycle 3. Elispot analysis was utilized to assess immunologic response, the primary endpoint. After reaching statistical significance, accrual to the more technically difficult IV arm was halted. Results: Of 21 patients enrolled, 20 have evaluable data points; 13 on the SQ arm and 7 IV. On the SQ arm, 9 of 13 (69%) patients had evidence for immunologic response. On the IV arm, 5 of 7 (71%) patients had an immunologic response. 42% on each arm experienced some grade III or IV toxicity (increased liver enzymes on the SQ arm and fatigue and lymphopenia on the IV arm), but only one patient disenrolled due to toxicity, a cardiac arrhythmia exacerbated by IL-2. Mean overall survival (to date) on the SQ arm is 70.4 months and on the IV arm is 72.9 months. Conclusions: The patients on this study were mostly heavily treated patients with short disease-free intervals, yet we demonstrated that immune responses can be generated against a wild-type protein epitope in a significant number of patients. Both vaccine approaches were similarly effective. This result should lead to a trial of early vaccination in high- risk patients to potentially delay or even prevent recurrence. No significant financial relationships to disclose. |
| Databáze: | OpenAIRE |
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