Abstract A16: A phase I/II clinical trial of a MUC1-glycopeptide dendritic cell vaccine in castrate resistant non-metastatic prostate cancer patients
Bibliographic record
Abstract
Abstract Background: Current treatment options for prostate cancer (PCa) patients with rising PSA despite castrate testosterone levels are limited. A number of immunotherapeutic approaches for the treatment of PCa have been studied with varying efficacy. MUC1 has been an antigen of interest for immunotherapy, however, tolerance to the peptide epitopes has led to limited immune response. A glycosylated version of the antigen, Tn-100mer-MUC1, was shown to be effective in overcoming tolerance in pre-clinical studies. Dendritic cells (DC) take up and process Tn-100mer-MUC1 and present both glycopeptide and peptide epitopes. We report the results of a phase I/II clinical trial of an autologous DC vaccine loaded with Tn-100mer-MUC1 and KLH in patients with castrate resistant, non-metastatic PCa. Methodology: Eight consenting patients with rising PSA were enrolled into the study; however one patient progressed with bone metastases before receiving the first vaccine dose. To generate the autologous DC vaccine, patient's monocytes were elutriated from apheresis product and cultured under conditions suitable for the generation of mature and motile DCs. Tn-100mer-MUC1 glycopeptide and clinical-grade KLH, as a control antigen, were loaded onto the DCs. The final vaccine product consisting of Tn-100mer-MUC1 and KLH loaded DCs mixed 10:1 was cryopreserved and tested before release and administration to patients. Patients were treated with 3 vaccine injections every two weeks administered intradermally (i.d.) and intranodally (i.n.) to a single inguinal node for the first dose only. Booster i.d. vaccinations were given 6 and 12 months following the first dose in patients showing stable disease. Each dose consisted of the administration of a total of 1.2 × 107 DCs. Toxicity and biologic effects of the vaccine were evaluated by physical, imaging and clinical chemistry examinations at regular intervals. PSA doubling times were determined using the Memorial Sloan-Kettering Cancer Center PSA doubling time calculator. Results: The vaccine was safe; there were no serious vaccine-related adverse events. Toxicity was limited to grade 1 and 2 injection site reactions. Four of 7 patients treated were withdrawn after 6 months because of radiologic progression or elevated PSA. Three patients showed stable disease and received all five vaccinations. Our primary endpoint, reduction in PSA, was not achieved. However, the rate of PSA rise decreased in 6 of 7 patients. Overall the PSA doubling time increased from a median of 2.9 months prior to treatment to 7.5 months during vaccination. Conclusions: These results suggest that the DC-Tn-MUC1 vaccination is safe and induces a biological response reflected by an increase in PSA doubling time in most patients. These early results are encouraging and warrant further testing in a larger number of patients. This study was supported by CANVAC with funds from the Networks of Centres of Excellence of Canada. Citation Format: Pierre Major, Louis Lacombe, Yves Fradet, Ronan Foley, Elizabeth Scheid, Alain Bergeron, Som Mukherjee, Olivera J. Finn, Jean Gariepy, Rafick P. Sekaly, Sebastien Hotte, Sheila Chou. A phase I/II clinical trial of a MUC1-glycopeptide dendritic cell vaccine in castrate-resistant nonmetastatic prostate cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A16.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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".