VB1-008: Identification of a fully-human antibody specific for CD44E and CD44-isoform-3
Bibliographic record
Abstract
2903 During the course of their disease, cancer patients often produce antibody responses to their tumors. Humoral tumor immunity has been correlated, in some cases, with a better prognosis and longer survival. Viventia’s product development platforms, Hybridomics™, ImmunoMine™, and UnLock™, have been designed to identify patient tumor-specific antibodies and their cognate tumor-associated antigen. One hybridoma-derived antibody, VB1-008, an IgG MAb, generated from the PBLs of a breast cancer patient, demonstrates preferential binding to the breast cancer tissues/cell lines as tested by immunohistochemistry and flow cytometry with limited normal tissue reactivity. Immunoprecipitation with tumor cell membrane fractions from VB1-008-reactive cell lines showed VB1-008 to react with a ∼110 kDa protein under mild reducing conditions that further resolved over time into one ∼50 kDa band following 1D and two spots varying in pI upon 2D-PAGE analysis. LC-MS/MS analysis of the 1D and 2D spots identified CD44-isoform-3/CD44E and a truncated version of alpha-fetoprotein (AFP). More specifically, with the use of overlapping peptides, VB1-008 reactivity was restricted to the peptide sequence-TNMDSSH, from the unique region constituting the junction of Exon 5 and the variable region, v8 of CD44-isoform-3 and CD44E. CD44E and CD44-isoform-3 differ from each other by only 2 amino acid changes at positions 221 and 230; however, conserving the epitope, TNMDSSH, in both. A synthetic peptide representing the sequence, TNMDSSH, conserved in both isoforms, competes 96% of the original binding by VB1-008. A similar peptide of the same length generated according to the sequence of variable regions v7-v8 of a parent isoform, CD44-isoform 2, MDMDSSH, showed no binding or competition to VB1-008. Extensive analysis by flow cytometry demonstrated that AFP was not present on the cell surface suggesting that this truncated version of AFP was associated with CD44 at the cytosol/membrane interface. The known over-expression of CD44E and CD44-isoform-3 with certain cancers validates the “mining” of the human immune response for the identification of fully-human antibodies specific for drugable cell surface tumor-associated target antigens.
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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 | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".