Abstract LB-269: Development of a vaccine model to track the CD8-specific response in Mauritius cynomolgus monkey
Bibliographic record
Abstract
Introduction Manipulating the immune system to achieve therapeutic efficacy in cancer treatment has led to a new class of drugs that brought lasting remissions to many patients who had run out of options. The development of new immunotherapy aimed at targeting cancer cells requires the ability to monitor specifically the immune response. Although CD8 T cells play a crucial role in this process, no equivalent of the traditional T-cell-dependent antibody response (TDAR) assay, which evaluates the T-helper immune response, is currently available. Since cancer immunotherapy agents are often tested in non-tumor bearing NHP for safety assessment, the animal models currently available do not allow monitoring of potential exaggerated pharmacology and efficacy of these new drug candidates.Objectives The goal of this study was to develop an NHP vaccination model that specifically elicits a CTL response, in order to evaluate the efficacy in exacerbating the Cytotoxic T Lymphocyte (CTL) response.Experimental Procedures To reach this goal, MHC-genotyped Mauritian cynomolgus macaques (MCMs) were immunized with 3 replication incompetent recombinant adenovirus serotype 5 (Ad5) vectors, each containing the coding sequence for Gag, Nef or Pol SIV proteins. Such model allowed monitoring of the CD8 T cell activation in lieu of a tumor or live virus model. MCMs were distributed into 3 groups: one control group and 2 groups which received two intramuscular injection of the adenovirusrs spaced by 4 or 8 weeks. The immune response was monitored with blood samples taken on a weekly basis for up to 12 weeks. Blood samples were used to 1) characterize the different CD8-positive sub-populations by Tetramer staining and Immunophenotyping; 2) to correlate the immunophenotyping profile obtained with functional assays such as ex vivo recall response and IFNγ ELIspot.Results Of the three groups tested, MCM monkeys receiving 2 injections 8 weeks apart showed the more robust CD8 T cell response. This response was mainly characterized by a proliferation profile (Ki67-positive cells), the expression of activation markers at the surface of CD8 T cells and antigen specific responses of the CD8 T cells. Of the three Gag, Pol and Nef proteins, immunization with Nef gave the most robust response, as observed by the IFNγ ELIspot results and by the presence of a Nef-specific CD8-specific subpopulation observed by tetramer staining. No changes in the distribution of T, B, NK, Treg or Memory T cells was observed between the 3 groups.Conclusion The results obtained during the course of this study suggests that the described CD8-specific vaccination model using Mauritius cynomolgus macaques is a promising model to evaluate the efficacy and potential exaggerated pharmacology of new drug candidates targeting CD8 T cells.Citation Format: Richard Graveline, Morad Haida, Carolyne Dumont, Rana Samadfam, Dominic Poulin, Marie-Soleil Piche. Development of a vaccine model to track the CD8-specific response in Mauritius cynomolgus monkey [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-269.
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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 | 0.001 | 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) | 0.002 | 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".