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| Ref Type | Journal Article | ||||||||||||
| PMID | (19621448) | ||||||||||||
| Authors | Leffers N, Lambeck AJ, Gooden MJ, Hoogeboom BN, Wolf R, Hamming IE, Hepkema BG, Willemse PH, Molmans BH, Hollema H, Drijfhout JW, Sluiter WJ, Valentijn AR, Fathers LM, Oostendorp J, van der Zee AG, Melief CJ, van der Burg SH, Daemen T, Nijman HW | ||||||||||||
| Title | Immunization with a P53 synthetic long peptide vaccine induces P53-specific immune responses in ovarian cancer patients, a phase II trial. | ||||||||||||
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| Abstract Text | The prognosis of ovarian cancer, the primary cause of death from gynecological malignancies, has only modestly improved over the last decades. Immunotherapy is one of the new treatment modalities explored for this disease. To investigate safety, tolerability, immunogenicity and obtain an impression of clinical activity of a p53 synthetic long peptide (p53-SLP) vaccine, twenty patients with recurrent elevation of CA-125 were included, eighteen of whom were immunized 4 times with 10 overlapping p53-SLP in Montanide ISA51. The first 5 patients were extensively monitored for toxicity, but showed no > or = grade 3 toxicity, thus accrual was continued. Overall, toxicity was limited to grade 1 and 2, mostly locoregional, inflammatory reactions. IFN-gamma producing p53-specific T-cell responses were induced in all patients who received all 4 immunizations as measured by IFN-gamma ELISPOT. An IFN-gamma secretion assay showed that vaccine-induced p53-specific T-cells were CD4(+), produced both Th1 and Th2 cytokines as analyzed by cytokine bead array. Notably, Th2 cytokines dominated the p53-specific response. P53-specific T-cells were present in a biopsy of the last immunization site of at least 9/17 (53%) patients, reflecting the migratory capacity of p53-specific T-cells. As best clinical response, stable disease evaluated by CA-125 levels and CT-scans, was observed in 2/20 (10%) patients, but no relationship was found with vaccine-induced immunity. This study shows that the p53-SLP vaccine is safe, well tolerated and induces p53-specific T-cell responses in ovarian cancer patients. Upcoming trials will focus on improving T helper-1 polarization and clinical efficacy. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| TP53 wild-type | ovarian cancer | no benefit | p53-SLP vaccine | Phase II | Actionable | In a Phase II trial, p53-SLP vaccine was demonstrated to be safe, well tolerated and to induce p53-specific T-cell responses in ovarian cancer patients; however clinical impact was lacking (PMID: 19621448, PMID: 21328579). | 21328579 19621448 |
| TP53 wild-type | ovarian cancer | predicted - sensitive | Ad.p53-DC vaccine | Phase I | Actionable | In Phase I and Phase II clinical trials, various forms of p53 gene therapy (such as adenoviral-p53) have been shown to be generally safe and have demonstrated clinical efficacy in patients with ovarian cancer (PMID: 12082455; PMID: 19621448; PMID: 21927947; PMID: 15297186; PMID: 12082456). | 15297186 21927947 19621448 12082455 12082456 |