Abstract LBA030: DPX-SurMAGE, a novel dual-targeted immunotherapy for bladder cancer, induces target-specific T cells with a favorable safety profile in preclinical model
Bibliographic record
Abstract
Abstract Thirty to forty percent of high-risk non-muscle invasive bladder cancer (NMIBC) fail standard of care, leaving radical cystectomy as the most recommended option for these patients. Therefore, new efficient and tolerable treatments are required to prevent or delay cystectomy. The DPX platform 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. Peptides that are packaged in DPX are specifically taken up by APCs. Maveropepimut-S (MVP-S, formerly known as DPX-Survivac) incorporates 5 HLA-restricted peptides derived from the anti-apoptotic protein survivin and is the first DPX-based immunotherapy. MVP-S demonstrated survivin-specific and sustained T cell response along with clinical activity and limited adverse events in patients with solid and hematologic tumors. Survivin and MAGE-A9 are well characterized tumor-associated antigens (TAAs) frequently overexpressed in bladder tumours. The DPX platform was leveraged to develop a new dual-targeted T cell activating immunotherapy, DPX-SurMAGE, incorporating HLA-A2 restricted peptides of both survivin and MAGE-A9. The feasibility of packaging peptides targeting two different TAAs into the DPX platform was assessed by performing comparative immunogenicity evaluation between 2 MVP-S peptides and DPX-SurMAGE in HLA-A2 transgenic mice. The magnitude of peptide-specific T cell responses against the shared HLA-A2 survivin peptide was similar in animals immunized with either DPX-SurMAGE or MVP-S indicating that the presence of MAGE-A9 peptides did not affect the immunogenicity of the MVP-S-based survivin peptide in the DPX-SurMAGE formulation. Immunogenicity and toxicity of DPX-SurMAGE with and without metronomic cyclophosphamide (mCPA) was further evaluated. IFN-γ ELISPOT assessment demonstrated robust induction of peptide-specific T cell responses to survivin and MAGE-A9 peptide pools. These strong responses were maintained at similar levels in the long-term chronic phase of the assessments both with and without mCPA. Preliminary safety observations including Detailed Clinical Examination (DCE), body weights and organ weights showed no sign of toxicity nor significant changes in mice treated with DPX-SurMAGE with or without mCPA. There were no significant differences in injection site reactions between DPX-SurMAGE groups (with and without mCPA). The local injection site reactions for DPX-SurMAGE groups were comparable to that of DPX-Empty control group. This study demonstrates the unique ability of the DPX delivery platform to deliver multiple antigenic TAA peptides without compromising the immunogenicity of each peptide. Furthermore, the DPX-SurMAGE treatment was well tolerated and was shown to induce robust and sustained target-specific T cell responses against both survivin and MAGE-A9 antigens, supporting the impending phase 1 clinical trial in high risk NMIBC patients. Citation Format: Valérie Picard, Valarmathy Kaliaperumal, Fanny Gaignier, Marjorie Besançon, Yogesh Bramhecha, Olga Hrytsenko, Alecia McKay, Stephan Fiset, Alain Bergeron, Yves Fradet. DPX-SurMAGE, a novel dual-targeted immunotherapy for bladder cancer, induces target-specific T cells with a favorable safety profile in preclinical model [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 LBA030.
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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 | 0.001 |
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".