Abstract 396: Reovirus successfully purges multiple myeloma <i>ex vivo</i> and does not affect human CD34+ cell engraftment in a murine transplantation model.
Bibliographic record
Abstract
Abstract Introduction: Multiple Myeloma (MM) is an incurable cancer that accounts for 10% of hematological malignancies. Stem cell rescue following high-dose chemotherapy with autologous or allogenic transplantation has become standard therapy for a subset of good performance patients. Previously we have shown that reovirus, a double stranded RNA virus can successfully purge the RPMI 8226 MM cell line, as well as a patient tumor specimen with no effect on stem cells (Thirukkumaran et al. 2004 : Blood. 102:377-387). In the present study we demonstrate 1) Efficient reovirus ex vivo purging of MM in a murine model of transplantation. 2) Reovirus purging does not affect human CD34+ stem cell repopulation or lineage differentiation. Methods: RPMI 8226-GFP MM cell line was admixed with human apheresis cells (AP) to represent 1% tumor burden. Admixed products were purged with live (LV) or UV-inactivated (DV) reovirus at a multiplicity of infection (MOI) of 40 for 72 hours. To assess purging efficacy and stem cell repopulating ability, SCID/NOD mice were sublethally irradiated and intraperitoneally injected with anti-asialo antibody to eradicate NK cells. Mice were injected intravenously with either live or dead virus purged admixed apheresis cells. Mice showing symptoms of disease were sacrificed and subjected to whole body fluorescence imaging using a GFP Imaging System. Bone marrow cells were collected from mouse femurs and analyzed for CD38+/138+/GFP+ MM cells. Human CD34+ stem cells were isolated from AP cells using Robosep (Stem Cell technologies) and exposed to LV or DV for 72 hours. LV (n=8) and DV (n=5) virus purged stem cells were mixed with sublethally irradiated (2Gy) AP cells (5X 105) and injected into irradiated SCID/NOD mice. Mouse blood and bone marrow was harvested at days 25 or 35 and assessed for human stem cells (CD34+/ 45+), T cells (45+/3+), B cells (19+/45+), NK cells(45+/3-/16+/33+) and myeloid (45+/13+/33+) cells. Results: 100% of LV purged animals (unlike DV purged) were devoid of MM and survived until being sacrificed arbitrarily at day 110 (Kaplan-Meier analysis: p< 0.0012). Both LV and DV purged human stem cells showed re-population in mice and lineage differentiation illustrating a lack of viral effect. Conclusions: The sensitivity of reovirus towards MM and its lack of effect on human stem cells highlight the potential of reovirus as an ex vivo purging agent during autologous hematopoietic stem cell transplants for MM. Currently, we are in the process of studying reovirus purging efficacy of ex vivo MM patient tumor in order to generate data for a future phase I clinical trial. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 396.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".