Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 45, 2004 4599 This study aims to model hyperacute rejection (HAR) in a small animal as a potential therapeutic approach to cancer. Hyperacute rejection is a rapid immunological response mediated by the binding of natural antibodies and the consequent activation of the complement cascade leading to cell lysis. Solid organ xenotransplantation from pig to old World primate results in HAR due to recognition of the galactose(α1,3)galactose (αGal) epitope present on porcine endothelial cells by primate anti-αGal natural antibodies. The αGal epitope is synthesised by the enzyme (α1,3)galactosyl transferase ((α1,3)GT) that is absent in humans. The eventual therapeutic goal in humans of HAR mimicry would be to deliver the (α1,3)GT gene to tumour endothelial cells leading to vascular destruction. An (α1,3)GT ko mouse has been generated that, analogous with humans, does not express αGal on the cell surface and produces anti-αGal IgM. Serum titres of anti-αGal IgM can be increased by intraperitoneal immunisation with hypotonically lysed rabbit red blood cells. Murine complement is less potent than human complement and serum from immunised (α1,3)GT ko mice must be augmented with exogenous rabbit complement in order that in vitro cytotoxicity against αGal positive murine endothelial target cells is equivalent to that of human serum. The (α1,3)GT ko mouse has been crossed with a nude mouse to create a double knockout to allow the growth of xenografted human tumours. Subcutaneous co-injection of irradiated (α1,3)GT retrovirus producer cells with human tumour cells causes in vivo transduction with (α1,3)GT and consequent αGal cell surface expression. Pseudotyping of the retroviral envelope results in selective transduction of either the stromal or tumour cell compartment. In experiments in progress the intravenous administration of serum from immunised (α1,3)GT ko mice and rabbit complement is expected to cause lysis by HAR of αGal positive murine stromal cells in tumour bearing nude/ko animals. This is analogous with the hyperacute rejection of αGal positive hearts seen in immunised (α1,3)GT ko mice after the administration of rabbit complement in transplantation experiments. The effect of the destruction of a small number of stromal and vascular cells is expected to be amplified and cause the destruction of a larger number of tumour cells. This should be manifest as a reduction in the rate of tumour growth and in the histological disappearance of αGal positive areas in treated animals in comparison with untreated controls. The validity of hyperacute rejection mimicry as a therapeutic strategy for cancer is based on the assumption that individuals with cancer have adequate levels and function of anti-αGal antibodies and serum complement proteins. This is currently under investigation experimentally in a group of 50 individuals and data will be presented to address this question.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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".