Development of lymphoid aggregates in metastatic uveal melanoma (mUM) tumors treated with tebentafusp
Bibliographic record
Abstract
Background: Cellular therapies using the adoptive transfer of T cells, such as patient-derived tumor-infiltrating lymphocytes (TILs), have demonstrated potential in effectively treating various types of cancer.Chemotherapy-based conditioning causes substantial morbidity and mortality, thereby significantly limiting the application of cellular therapies.Methods: Here, we present an alternative to conventional conditioning by replacing chemotherapy and interleukin (IL) 2 with arenavirus-based virotherapy.We use adoptive transfer of T-cell receptor transgenic T cells recognizing the melanocyte differentiation antigen TRP2 and the B16F10 murine melanoma model.Results: Our results demonstrate that arenavirus-based virotherapy has an excellent safety profile and maintains efficacy of cellular therapy.We show complete rejection of established melanomas after conditioning with the replicating lymphocytic choriomeningitis virus carrying TRP2 (artLCMV-TRP2), without prior lymphodepletion or addition of IL-2.We further show that replication of the virotherapy is needed for lasting tumor control.Our data indicate that artLCMV induces activation and expansion of transferred T cells significantly more efficiently than the replicating Pichinde virus (artPICV), translating into complete rejection of established melanomas.artLCMV carrying a non-tumor antigen is unable to control tumor growth.Conclusions: We identify three key factors required for effective conditioning using virotherapy: virus replication, virus type, and antigen identity.Our study establishes virotherapy as a promising alternative to conventional conditioning in cellular immunotherapies.This approach demonstrates significant antitumor efficacy with an improved safety profile.
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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) | 0.001 | 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 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".