Caulobacter in cancer immunotherapy
Bibliographic record
Abstract
A60 Purpose: To develop new cancer vaccine formulations using both the wild type (WT) and genetically modified Caulobacter crescentus (CC).Methods: Murine mammary carcinoma (EMT-6) cancer cell line was employed to investigate the anti-tumour effects of CC in two groups. In-vivo comparison of the effect of routes of administration on the antitumor effect of WT CC against EMT-6 was investigated. In-vivo comparison of the antitumor effects of the single and double mutant bacterial strains against EMT-6 was also performed. These include the CB15A KASC which is an S-layer minus strain, but still has the Smooth Lipopolysaccharides (LPS) and CB15A Ca5 KSAC which is a strain that has no S-layer and has a point mutation in the Smooth LPS. This latter strain can be referred to as the “naked” Caulobacter control. Natural killer (NK) cells from mice were isolated using magnetic activated cell separation from splenocytes using anti-NK cellanti-CD49b (DX5)microbead separator. Purified NK cells were co-incubated with WT CC, purified LPS, isolated S-layer protein ormouse interleukin-2 (IL-2).The cell-free supernatants from pooled cultures were collected for Enzyme Linked ImmunoSorbent Assay (ELISA) for interferon-gamma (IFN-γ) secretion. We developed a new active specific immunotherapy approach with high density display of MUC-1 breast cancer tandem peptide repeats on the S-Layer of CC.Results: WT treated mice showed a lower tumour volume with longer survival rate, when compared to the control group. Antitumor efficacy was higher in mice treated with intraperitoneal route than in intratumoral route of treatment. Normal saline treated and the double mutant control treated groups, exhibited high relative tumour volume and short survival rates compared to the WT bacteria and the single mutant strain treated groups. The latter showed a prolonged survival rates as well as reduced tumour volume. Thus, the results suggest that CC smooth LPS might be responsible for the bacteria anti-tumour activity. CC LPS directly stimulates pro-inflammatory cytokine IFN-γ production by NK cells. The in-vitro immunochemical characterization of the new designer high-density expression of multimeric-MUC-1 on CC display of cancer peptides using B27.29 monoclonal antibody against MUC-1 antigen using standard whole cell ELISA and SDS-PAGE analysis were established. Conclusion:CC may be a safe, bacterial immunomodulator for the treatment of tumors. The non-toxic and highly immunogenic CC-LPS play a key role in the inherent antitumor effect of the bacteria. Finally, CC is also valuable as a “platform” for particulate whole cell expression and presentation of MUC-1 peptide. Acknowledgement: The project is supported by the Natural Sciences and Engineering Research Council of Canada Collaborative Health Research Project (NSERC-CHRP).
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".