Safety toxicology of an IL-2 ‘no-alpha’ mutein in the Sprague-Dawley rat following repeated dosing via intravenous administration
Bibliographic record
Abstract
The potential toxicity, safety and anti-drug antibody production of the novel IL-2 "no-alpha" mutein is in need of investigation as it may be a critical candidate for cancer therapy. The design of this mutein is meant to reduce toxicity compared to the IL-2 wildtype by disrupting interactions with the alpha receptor (CD25) and increasing the efficacy of the treatment. This was assessed following administration to Sprague-Dawley rats intravenously (IV), and it occurred over three cycles of five days each with daily dosing, with a 9-day washout period between each cycle. For the mutein dose groups, animals were dosed via IV at dose levels of 600, 6000, 18,000 U/kg. This dosing regimen is equivalent to 1x, 10x, and 30x the proposed first human dose, respectively. This study also assessed the progression or regression of any effects following a 14-day treatment-free recovery period for the control and high dose groups. Rats that were administered the "no-alpha" mutein at 600 and 6000 U/kg were well-tolerated with no apparent abnormal observations in general health, behaviour and autonomic function. There was no evidence of systemic toxicity based on evaluations in clinical pathology, gross necropsy and histopathology. At 18,000 U/kg (30x), abnormal clinical signs were observed at the injection sites consisting of localized swelling, discoloration, scabbing and necrosis. These animals showed a significant recovery in abnormal localized clinical signs following the treatment free period. Additionally other parameters did not indicate any significantly detrimental effects at this dose level. Therefore, the IL-2 mutein "no-alpha" seems to hold promise as a valuable addition to the current array of cancer therapy strategies, especially at the proposed dose level.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 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".