Antitumor Effect of G3139 Bcl-2 Antisense Oligonucleotide Is Independent of Its Immune Stimulation by CpG Motifs in SCID Mice
Bibliographic record
Abstract
The Bcl-2 antisense oligonucleotide (AS-ODN) G3139 chemosensitizes human malignancies by downregulating the antiapoptotic protein Bcl-2. Because G3139 contains two potential immunostimulatory CpG motifs, we asked if immune stimulation contributes to the antitumor activity observed previously. 5'-Methylation of cytosines in CpG motifs abrogates immune stimulation by oligonucleotides. We, therefore, studied the antitumor and immunostimulatory potential of G3139 vs. an identical oligonucleotide, except for methylation of cytosines in the two CpG motifs (G4232). In a human melanoma SCID mouse xenotransplantation model, G3139 or G4232 was administered by continuous subcutaneous (s.c.) or bolus intraperitoneal (i.p.) infusion. Both G3139 and G4232 significantly reduced tumor growth by about one third relative to the saline-treated group. Furthermore, we noted a similar downregulation of Bcl-2 expression and increase in tumor cell apoptosis caused by G3139 and G4232 compared with saline controls. However, mice treated with G3139 had a pronounced increase in spleen weight and interleukin-12 (IL-12) plasma levels relative to mice treated with either G4232 or saline. Splenomegaly and elevated IL-12 plasma levels suggest that G3139 can be immunostimulatory. However, there is clear evidence that the antitumor effect of G3139 in this model appears to be a Bcl-2 antisense effect that is independent of immune stimulation, as G3139 and its immune-silent counterpart G4232 caused similar tumor suppression and apoptosis induction.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".