Abstract 1778: Nimotuzumab, a humanized antiepidermal growth factor receptor antibody, interacts with EGFRvIII
Bibliographic record
Abstract
Abstract Introduction: Glioblastomas frequently overexpress a variant form of EGFR, called variant III (EGFRvIII), which has an in-frame deletion of an 801-bp sequence in the extracellular domain. EGFRvIII does not bind EGF ligand but exhibits constitutive kinase activity that results in enhanced transformation, reduced apoptosis, and resistance to therapy. Nimotuzumab (Nmab) is an EGFR-targeting antibody that has demonstrated encouraging results in early clinical trials treating adult and pediatric brain tumors. Here we present data characterizing the interaction of Nmab with EGFRvIII. Methods: Binding of Nmab to the extracellular domain of wtEGFR and EGFRvIII was first characterized by SPR biosensor analysis: Nmab was captured via its Fc domain and varying concentrations of EGFRvIII and EGFRwt were flowed. Flow cytometry analysis was subsequently performed using a parental U87MG glioblastoma cell line and derivatives which were engineered to overexpress either wtEGFR or EGFRvIII. Results: Nmab bound EGFRvIII and EGFRwt with similar affinity, which was in the 10−8 M range. This KD is consistent with the previously reported affinity constant of Nmab for EGFRwt (Telavera et al, 2009). Binding was further analyzed by flow cytometry. Nmab bound both EGFRwt and EGFRvIII expressed on the surface of parental U87MG, U87MG EGFRvIII and U87MG wtEGFR cells. Additional data concerning effects of Nmab on EGFRvIII expressing cell lines will be presented. Conclusion: Nmab binds to wtEGFR and EGFRvIII with similar affinity, which supports development of the antibody as a therapeutic for glioblastoma. In U87MG glioblastoma cells, synergistic activity of Nmab in combination with radiotherapy has been previously reported (Diaz Miqueli et al, 2009). Nmab is currently being tested in an advanced randomized study in the first line setting for the treatment of adult glioma. Nmab is being tested in combination with radiation plus temozolomide, vs radiation plus temozolomide alone, with preliminary results expected in the second half of 2010. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1778.
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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 | 0.000 | 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) | 0.003 | 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".