Adeno‐Associated Viral Vectors for Homology‐Directed Generation of CAR‐T Cells
Bibliographic record
Abstract
Immunotherapy with T cells expressing chimeric antigen receptors (CAR) is an emerging and promising treatment against refractory cancers. However, the currently adopted methods of modification of T cells pose a risk of insertional oncogenesis because lentiviral and retroviral vectors integrate the CAR transgene in a semi-random fashion. In addition, this therapy is only available using autologous cells, which create problems in production and limit the access for patients who have their T cells depleted. One modification method that shows the ability to overcome both drawbacks is the knock-in of the CAR simultaneously knocking-out genes that prevent allogeneic therapy, such as the endogenous T cell receptor. In this mini-review, the authors present recent efforts to develop safer universal CAR-T cells. More specifically, the combined application of target-directed nucleases, which create a double-strand break at a specific genome locus, and the delivery of CAR DNA via adeno-associated viral vectors for subsequent integration via homologous recombination and silencing of the targeted gene is focused on.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.004 |
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".