Study of TBI-1301 (NY-ESO-1 specific TCR gene transduced autologous T lymphocytes) in patients with solid tumors
Bibliographic record
Abstract
Background: The use of cell based immune therapies involving infusion of autologous T-lymphocytes with anti-tumor activity targeting tumor-associated antigens is a rapidly evolving area of research. One approach involves the use of peripheral blood as a source of lymphocytes that are then used in the generation of cytotoxic tumor-specific T cells via introducing a tumor-specific TCR gene into T lymphocytes. NY-ESO-1 is a cancer testis antigen expressed in numerous cancers yet absent in most adult normal tissues apart from high expression in adult testes – thereby making it an ideal target for immunotherapy. Trial design: TB1-1301 is a gene-modified T cell product that contains a NY-ESO-1 specific TCR introduced with the MS3II-NY-ESO1-SiTCR retroviral vector. This vector encodes for TCR α and β chains that recognize an NY-ESO-1 derived epitope (amino acids 157-165: SLLMWITQC) that is presented in the context of HLA-A*02:01 and HLA-A*02:06 molecules. The vector also encodes for siRNA (small interfering RNA) that are homologous to the constant region sequence of the endogenous, but not transduced TCR α and β chain mRNAs – these siRNAs in turn increase expression of the transduced TCR. Pre-clinical murine studies demonstrated safety, persistence, and efficacy of transduced T cells. This study represents a Phase 1b study of TBI-1301 in patients with advanced solid tumors, which express NY-ESO-1 (synovial sarcoma, ovarian cancer, and melanoma). A pre-conditioning lymphodepletion regimen of cyclophosphamide 750 mg/m2 will be used on Day -3 and Day -2 prior to infusion of cell product. The objectives of this study include assessing the safety profile of TBI-1301, determining the RP2D dose, and evaluating the efficacy of TBI-1301 via RECIST v1.1. Clinical trial identification: NCT02869217. Legal entity responsible for the study: Tumor Immunotherapy Program, Princess Margaret Cancer Centre. Funding: Takara Bio Inc. Disclosure: M.O. Butler: Advisory boards: Merck Canada, BMS, Novartis, Immunocore, Immunovaccine, GSK; Research support: Takara Bio Inc. conducting this clinical trial. S. Tanaka: Employee: Takara Bio Inc. N. Hirano: Research support: Takara Bio Inc. All other authors have declared no conflicts of interest.
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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) | 0.001 | 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 | 0.001 |
| 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".