Abstract A84: Metronomic cyclophosphamide, when combined with vaccination, increases the immunogenicity of the vaccine and modulates the tumor microenvironment to provide better anti-tumor activity
Bibliographic record
Abstract
Abstract DPX-Survivac is a peptide vaccine targeting the broadly expressed tumor antigen survivin. The vaccine contains a mixture of survivin HLA class I peptides (A1, A2, A3, A24 and B7) formulated in the novel adjuvanting vaccine platform DepoVaxTM. A phase I clinical study performed in advanced ovarian cancer patients (n=19) demonstrated that the combination of metronomic cyclophosphamide (mCPA) and DPX-Survivac exhibited enhanced immune responses by IFN-γ ELISPOT (p<0.015) and increased poly-functional antigen-specific EM/ CM CD8+ T cells, relative to patients treated with vaccine alone. These results were mirrored in a preclinical mouse model in which tumor bearing mice treated with mCPA in combination with a DPX peptide vaccine had increased IFN-γ ELISPOT response and enriched antigen-specific CD8+ T cells. Adoptively transferred T cells from mice treated with the combination of mCPA and vaccine provided a more pronounced anti-tumor effect. Immunophenotyping by flow cytometry indicated that mice treated with mCPA and vaccine had reduced levels of tumor-induced immune suppressor cells, such as myeloid derived suppressor cells, but no effect was seen on regulatory T cells. Analysis of the tumor microenvironment by RT-qPCR revealed that mice treated with combination therapy had increased levels of cytotoxic T lymphocyte (CTL) markers such as granzyme B and IFN-γ. An ovarian tumor model (MOSE) was developed in HLA-A2 transgenic mice to extend these finding to a DPX-survivin vaccine in a relevant animal model. We showed that mCPA increased the levels of CTL markers in the tumor specifically when combined with a DPX-survivin vaccine, in addition to enhancing the immunogenicity of the vaccine. Together, these models allow us to explore novel immune modulator/ vaccine combinations and provide insight into mechanisms that could result in enhanced anti-tumor activity. Citation Format: Genevieve M. Weir, Neil L. Berinstein, Olga Hrytsenko, Mohan Karkada, Marianne M. Stanford, Marc Mansour. Metronomic cyclophosphamide, when combined with vaccination, increases the immunogenicity of the vaccine and modulates the tumor microenvironment to provide better anti-tumor activity. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A84.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".