Abstract 1449: MG1 Maraba boost following adenovirus prime generates tumor antigen-specific T cells which are potentiated by anti-PD-1 antibody combination
Bibliographic record
Abstract
Immune checkpoint inhibitors, such as antibodies blocking PD-1 and PD-L1, have been shown to potentiate pre-existing immune responses and improve patient survival. MG1 Maraba is a novel oncolytic virus that we bioselected and engineered to cause cancer cell death through two distinct and complementary mechanisms-of-action, direct cancer lysis and tumor-antigen specific T cell generation. MG1 Maraba encoding tumor antigens has been demonstrated to boost pre-existing immune responses. We are currently using a non-replicating adenovirus as the priming entity in our ongoing preclinical and clinical studies for our MG1 Maraba product candidates. This therapeutic platform is able to generate a large number of highly-functional antigen-specific T cells, in addition to its oncolytic activity, in mice, non-human primates (NHP) and patients treated with Adenovirus and oncolytic MG1 Maraba, expressing the same tumour associated antigen. This study investigates the ability of αPD-1 to potentiate immune responses generated by Ad/MG1 prime/boosting, and whether the timing of αPD-1 administration impacts the immune responses and therapeutic outcome. The combination of αPD-1 and Ad/MG1 treatment was investigated in a challenging murine model of metastatic melanoma. In three independent experiments, mice bearing advanced B16F10 lung metastases treated with Ad/MG1-hDCT in combination with αPD1 antibody, overall survival was increased to greater than 90%, compared to survival rates of less than 40% in mice treated with Ad/MG1-hDCT alone. The increased efficacy was correlated with improved anti-tumour immune responses in the αPD-1 combination group. The strongest effects of αPD-1 were observed when αPD-1 treatment was initiated immediately following Ad-hDCT immunization leading to significantly increased anti-tumour immune responses at all timepoints analyzed. When delayed until 1 week after MG1 treatment, αPD-1 was unable to improve the anti-tumour immune responses, or therapeutic efficacy, elicited by Ad/MG1 treatment. Similar effects were observed using an αPD-L1 targeted antibody. Therefore, the timing of PD-1/L1 blockade during Ad/MG1 treatment was determined to be a critical parameter for successful therapeutic outcomes. In addition, a non-human primate study is underway to assess the combination of αPD-1 with Ad/MG1-E6E7 (expressing HPV E6 and E7) when delivered concurrent with adenovirus immunization. Moreover, these data highlight the timing of checkpoint inhibitor treatment as a critical parameter for consideration when administering immune checkpoint inhibitors with other agents, including oncolytic viral immunotherapies.Citation Format: Kyle Stephenson, Kwame Twumasi-Boateng, Amy Patrick, Caroline Breitbach, Michael Burgess, Brian Lichty. MG1 Maraba boost following adenovirus prime generates tumor antigen-specific T cells which are potentiated by anti-PD-1 antibody combination [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 1449.
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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) | 0.000 | 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 | 0.001 |
| 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".