Abstract LBA026: Survivin peptides formulated in the DPX delivery platform rather than standard emulsions, elicit a robust, sustained T cell response to survivin in advanced and recurrent ovarian cancer patients
Bibliographic record
Abstract
Abstract Despite improvements in peptide-based tumor antigen discovery, success in eliciting a clinically meaningful T cell response to these peptides has been limited. The choice of antigen delivery platform strongly impacts the quality, quantity, and durability of induced immune responses. DPX is a unique, water-free, lipid-based formulation that can deliver peptides, proteins, and small molecules specifically to antigen presenting cells (APCs), eliciting a targeted, robust, and sustained T cell-based immune response. DPX allows for antigenic peptides to remain at the site of injection without significant diffusion into surrounding tissues, in direct contrast to most emulsion-based delivery methods. Maveropepimut-S (MVP-S; formerly known as DPX-Survivac) is a DPX formulation that incorporates 5 HLA-restricted peptides derived from the anti-apoptotic protein survivin, which is commonly overexpressed in advanced cancers including ovarian cancer. Prior efforts with these same peptides emulsified in Montanide ISA 51 VG provided limited clinical benefit and no objective responses (Lennerz 2014). We now show in pre-clinical models that, when packaged in DPX, these peptides elicit higher avidity, more abundant and cytolytically-active survivin-specific T cells than standard emulsion-based formulations. Early clinical studies with MVP-S in advanced ovarian cancer patients have shown a persistent, survivin-specific T cell response, which in a subset of patients lasted more than 2 years. The recently completed phase 2 study of MVP-S and low-dose cyclophosphamide (CPA) in advanced and recurrent ovarian cancer subjects (DeCidE1), provided encouraging clinical benefit across multiple measures (ORR = 26% & DCR = 79% on target lesions, mOS = 19.9 months in evaluable patients). We now show that majority of patients in this study had survivin-specific T cells on treatment by in vitro tetramer staining (87%) and ex vivo ELISPOT analyses (56%). Importantly, 75% of patients deriving clinical benefit had active survivin-specific T cells by ex vivo ELISPOT analyses. Immunophenotyping of the longitudinally collected PBMCs showed evidence of sustained T cell proliferation by tetramer staining across time and did not show increased expression of immunosuppressive markers (e.g., PD-1, Tim3), suggesting that MVP-S induced T cells remain active over time. TCRβ analyses of tumor TCR repertoires further showed the ability of de novo elicited survivin-specific T cells to infiltrate on-treatment tumours. Collectively, these preclinical and clinical data show that MVP-S treatment effectively elicits a robust, persistent, survivin-specific T cell response. These data also provide compelling evidence that clinical benefit in DeCidE1 patients is most evident in those with survivin-specific T cells. Finally, these data further underscore the unique capacity of DPX technology to effectively elicit peptide-specific, T cell based immune responses when conventional formulations do not. Citation Format: Yogesh Bramhecha, Oliver Dorigo, Valarmathy Kaliaperumal, Heather Torrey, Walead Ebrahimizadeh, Kelcey Patterson, Brennan Dirk, Moamen Bydoun, Barry Kennedy, Aurelio Lobo, Genevieve Weir, Jeremy Graff, Stephan Fiset, Olga Hrytsenko. Survivin peptides formulated in the DPX delivery platform rather than standard emulsions, elicit a robust, sustained T cell response to survivin in advanced and recurrent ovarian cancer patients [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA026.
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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 | 0.001 |
| 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".