Improved Treatment of Pancreatic Cancer by IL-12 and B7.1 Costimulation: Antitumor Efficacy and Immunoregulation in a Nonimmunogenic Tumor Model
Bibliographic record
Abstract
Ductal pancreatic adenocarcinoma is one of the commonest and most lethal cancers in the Western world. Unfortunately, recent advances in diagnostics, staging, and therapy in pancreatic carcinoma have not resulted in significant improvements in long-term survival. We have previously shown that adenovirus (Ad)-mediated coexpression of interleukin-12 (IL-12) and the costimulatory molecule B7.1 is extremely efficient in inducing regression of highly immunogenic transplanted and nontransplanted tumors. Here, we examined the antitumor efficacy of IL-12- and B7.1-based immunotherapy against a nonimmunogenic murine model of ductal pancreatic cancer. Compared with AdIL-12 treatment alone, single intratumoral injection of AdIL-12/B7.1 led to a prolonged immune response and mediated complete regression in 80% of treated animals. After rechallenge with parental tumor cells, 70% of cured mice remained tumor-free, suggesting that protective immunity had been induced. The antitumoral response was associated with upregulation of H-2K(b) and Abcb2 expression, whereas other components of the proteasome (Abcb3, Psmb9, and Psmb8) were not affected. These data indicate that upregulation of the antigen presentation machinery by AdIL-12/B7.1 may be a therapeutic rationale for nonimmunogenic, therapy-resistant pancreatic cancer.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".