Abstract 1793: 5-Fluorouracil chemotherapy acts synergistically with adoptive dendritic cell immunotherapy to induce durable anti-tumor responses <i>in vivo</i>
Bibliographic record
Abstract
Abstract Introduction: 5-Fluorouracil induces a form of cell death that facilitates the presentation of antigens by dendritic cells and depletes myeloid suppressor cells in vivo. The resulting immune modulation plays a substantial role in prolonging survival of mice with cancer. Our lab has previously demonstrated that a fusion of granulocyte-colony macrophage-stimulating-factor (GM-CSF) and Interleukin (IL) – 21, hereafter GIFT-21, could differentiate monocytes into a novel dendritic cell population (GIFT-21 DC). Characterization of these cells revealed a unique phenotype, with the expression of markers normally associated with both conventional and plasmacytoid dendritic cells. They are effective at cross-presenting antigens and secrete substantial amounts of CCL2, IL-6, TNF-α and IFN-α. When injected into tumor-bearing mice, they migrate to and sample from tumors in vivo, allowing them to educate CD8 T cells to recognize tumor antigens, which then significantly impeded the growth of B16 and D2F2 Neu tumors in mice. Hypothesis: We propose that 5-Fluorouracil mediated immune modulation can be combined with adoptively transferred autologous GIFT-21 DCs to treat established cancer, and lead to a synergistic anticancer immune response. Methods and Results: Twelve days following a subcutaneous tumor implantation, mice with established B16 tumors (average volume of 40mm3) were treated daily with 1.5 mg 5-Fluorouracil for 2 days and then injected on the third day with 1.5×106 syngeneic GIFT-21 DCs intraperitoneally. The treatment was repeated one week later. While 5-FU treatment alone or dendritc cell therapy alone had no significant impact on the growth of pre-established melanoma, the combination of 5-Fluorouracil with GIFT-21 DC-based immunotherapy reduced the rate of tumor growth by 75% over 5-FU and 85% over untreated mice, while eventually leading to the regression of the pre-established B16 tumors. Conclusion: These findings demonstrate how chemotherapy can be combined with immunotherapy to target cancers for which tumors antigens are unknown or ill-defined. While chemotherapy suppresses some elements of the immune system in the short term, we speculate that modulating the endogenous immunological processes secondary to chemotherapy shows promising synergy with adoptive cell therapy and is a promising avenue of future research in cancer immunotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1793. doi:10.1158/1538-7445.AM2011-1793
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 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) | 0.002 | 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".