Using comparative oncology approach to develop radioimmunotherapy for osteosarcoma
Bibliographic record
Abstract
1222 Introduction: Osteosarcoma (OS) is the most common primary malignant bone tumor and the fifth most common primary malignancy among adolescents and young adults. In over 30 years, the five year overall survival has remained static at approximately 70% with no significant advancement in treatment options. In addition, OS demonstrates sweeping genetic variability from one tumor to the next which makes it challenging to pursue conventional targeting approaches. The cation independent mannose-6-phosphate/insulin-like growth factor-2 receptor (IGF2R) was recently found to be consistently overexpressed on multiple standard and patient-derived OS cell lines, making it a promising therapeutic target. Radioimmunotherapy (RIT) is a method wherein an antigen-specific antibody conjugated with an alpha- or beta-emitting radioisotope delivers cytotoxic radiation in a targeted fashion. This technique can be a novel treatment for OS. Interestingly, OS is one of the most widespread cancers in companion dogs and very closely resembles human OS. Treatment for dogs with OS is limited. Therefore, for this project, we aim to create a novel, effective and safe treatment for patients with metastatic OS based on radioimmunotherapy and utilizing comparative oncology approach. Methods: We used phage-display approach to develop human antibodies that are specific for human IGF2R and is cross-reactive with similar affinities to murine and canine versions of IGF2R. The generated antibodies were tested for tumor binding in SCID mice bearing human and canine tumor grafts. Results: Several Fab’ and full antibodies cross-reactive with IGF2R from human, dogs and mice were generated. When radiolabeled with 111In - these antibodies bound to human and canine grafted tumors in mice as confirmed by microSPECT/CT imaging. Conclusions: Future studies will involve radiolabeling best binding antibodies with 177Lu to target OS tumor cells in the experimental OS in mice first, and then in companion dogs with OS and to deliver curative tumoricidal doses of radioactivity to the tumors without toxicity to normal organs.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".