Effect of oral cyclophosphamide on the immunogenicity of DPX-Survivac in ovarian cancer patients: Results of a phase I study.
Bibliographic record
Abstract
3030 Background: Survivin, a protein involved in regulation of apoptosis, is highly expressed in many tumor types and has reported prognostic value. DPX-Survivac is a cocktail of survivin HLA class I peptides (A1, A2, A3, A24 and B7) formulated in the novel adjuvanting vaccine platform DepoVax. A phase I study examined the safety and immune potency of DPX-Survivac in combination with cyclophosphamide in ovarian cancer patients. Methods: 18 of 19 advanced ovarian cancer patients treated with platinum chemotherapy and showing no disease progression completed their vaccine therapy. Cohort A (6 pts) received three 0.5 mL vaccine injections 3 weeks apart; cohorts B and C (6 pts each) received three 0.1 mL or 0.5 mL vaccine injections in combination with metronomic low dose oral cyclophosphamide. Adverse events were assessed using CTCAE v4.0. Blood was collected to study immune function (MDSCs, T regs and B cells) and vaccine-induced T cell immunity (ELISpot, tetramer analysis and multi-parametric intracellular cytokine staining). Repeated measures of immunity at baseline and after 1, 2 and 3 injections were analyzed using a general linear model. Results: DPX-Survivac was well tolerated with no significant systemic AEs. Local injection AEs occured in all patients. Grade 3 local reactions occured in 3 patients (1 pt in B and 2 pts in C). 11 of 12 patients receiving the combination therapy produced immune responses by at least 2 assays, generally established with one or two vaccinations and increased or maintained with boosters. A dose response was observed, with cohort C patients producing significantly higher magnitude responses (C vs B, P=.013). Low dose cyclophosphamide significantly enhanced the 0.5 ml dose (C vs A, P=.015). Notably, antigen specific CD8 T cells were detected ex vivoi n PBL’s using tetramers and further characterized as polyfunctional by multi-parametric ICS, suggesting a robust immune response. Conclusions: DPX-Survivac is well tolerated and immunogenic. Immune modulation with low dose oral cyclophosphamide can dramatically enhance the immunogenicity of this vaccine. The efficacy of the proposed DPX-Survivac vaccine therapy needs to be tested in a randomized phase II study. Clinical trial information: NCT01416038.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".