Dendritic cells engineered to express the Flt3 ligand stimulate type I immune response, and induce enhanced cytoxic T and natural killer cell cytotoxicities and antitumor immunity
Bibliographic record
Abstract
BACKGROUND: Tumor antigen presentation by dendritic cells (DCs) to T cells in lymphoid organs is crucial for induction of antitumor immune responses. Fms-like tyrosine kinase 3 ligand (Flt3L) is a regulator of hematopoietic cell development. METHODS: To investigate the potential effect of Flt3L transgene expression on DC-based cancer vaccines, we constructed a recombinant adenovirus AdVFlt3L expressing Flt3L, transfected DCs with AdVFlt3L, and investigated the efficacy of antitumor immunity by vaccination of DC(Flt3L) engineered to express Flt3L transgene. RESULTS: Our data demonstrated that AdVFlt3L transfection up-regulated the expression of cytokine IL-1beta and chemokines MIP-1alpha, MIP-1beta, IP-10, MCP-1 and MIP-2, and stimulated DC(Flt3L) cell proliferation in vitro and migration toward regional lymph nodes in vivo. Our data also demonstrated that vaccination of Mut1-pulsed DC(Flt3L) cells was able to stimulate (i). a type 1 immune response comprising CD4(+) Th1 and CD8(+) Tc1 activation and (ii). around 2- and 3-fold enhanced tumor-specific cytotoxic T lymphocyte (CTL) and non-specific NK responses (p < 0.05) than vaccination with similarly pulsed control virus-transfected and untransfected DCs, respectively. More importantly, vaccination of Mut1-pulsed DC(Flt3L) cells induced enhanced antitumor immunity in vivo, even against poorly immunogenic 3LL tumor cells. Vaccinations of Mut1-pulsed DCs, DC(pLpA) and DC(Flt3L) all protected mice from challenge of low dose (0.5 x 10(5)) tumor cells. However, only vaccination of the last one was able to protect 63% (6/8) mice from challenge of high dose (3 x 10(5)) 3LL tumor cells (p < 0.01). CONCLUSIONS: DCs engineered to secrete Flt3L may offer a new strategy in DC-based cancer vaccines.
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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 | 0.002 | 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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".