P06.15.B IMMUNOTHERAPEUTIC TARGETING OF FIBROBLAST ACTIVATION PROTEIN (FAP) IN TREATMENT REFRACTORY GLIOBLASTOMA USING NOVEL CAR-T CELL THERAPY
Bibliographic record
Abstract
Abstract BACKGROUND Glioblastoma (GBM) is the most common malignant primary adult brain tumor, characterized by extensive cellular and genetic heterogeneity. The Standard of Care (SOC) therapy and clinical trials have not been successful in improving patients’ survival which underscores an urgent need for developing new effective therapies for this treatment refractory disease. MATERIAL AND METHODS In silico and in vitro analysis have revealed high level of Fibroblast Activation Protein (FAP) expression in GBM tissue in multiple cell populations including endothelial cells, fibroblasts, stromal cells and tumor cells, but not on normal brain tissue, making FAP a safe and suitable therapeutic target as it allows for destruction of tumor cells as well as effective elimination of their supporting microenvironment. As Chimeric antigen receptor (CAR) expressing T cells have shown promising results against multiple cancers in the past few years, we aimed to target FAP in GBM by FAP specific CAR-T cells generated using a novel GMP-ready FAP-CAR construct produced based on a virus-free CAR gene transfer using advanced sleeping beauty transposon technology and preclinically test their anti-tumor efficacy against GBM at in vitro and in vivo level. RESULTS Our data revealed that co-culturing CAR-T cells with FAP+ GBM cells (U87) results in increased surface expression of T-cell activation markers. Moreover, FAP CAR-T mediated cytotoxicity against FAP+ GBM cells was also observed in the co-culture of GBM and CAR-T cells. For further validation, the effect of FAP CAR-T cells will be tested on patient-derived GBM organoids. The in vivo efficacy of FAP CAR-T cells is currently under investigation and we anticipate that the treatment of GBM tumor-bearing mice with FAP CAR-Ts results in extended survival and reductions of tumor burden. CONCLUSION These rigorously obtained data show high level of efficacy for FAP-specific CAR-T cells against GBM suggesting that clinical development of this therapeutic modality can provide a novel therapeutic strategy for GBM patients that can be used in combination with SOC or other immunotherapeutics. Therefore, upon successful completion of the preclinical study, we plan to conduct a phase I dose-escalation trial of autologous FAP-CAR T cells for patients with recurrent Glioblastoma.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".