Abstract 623: NK cells are involved in promoting anti-tumor responses to DPX-peptide immunotherapy
Notice bibliographique
Résumé
Abstract DPX™ technology is a non-aqueous, immune-educating therapeutic platform that delivers specific instruction to the immune system. Antigenic peptides can be packaged within DPX to elicit a robust and persistent tumor antigen-specific T cell response. Maveropepimut-S (MVP-S), formerly DPX-Survivac, contains 5 peptides derived from the tumor antigen survivin, as well as poly dIdC and a T helper peptide. In clinical trials, MVP-S consistently incites a robust and persistent, survivin-specific immune response and promotes T and B cell infiltration into tumor tissues. Importantly, MVP-S based therapy has provided compelling evidence for clinical benefit in multiple cancer indications, notably DLBCL and ovarian cancer. Herein, we provide the first evidence from clinical and preclinical studies that Natural Killer (NK) cells are involved in the anti-cancer efficacy of DPX-based therapy. We evaluated clinical samples from the DeCidE1 trial in advanced, recurrent ovarian cancer (NCT02785250). RNA-profiling of immune cells within tumor tissue revealed the presence of both activated and resting NK cells. Prior to treatment, activated NK cells were more evident in samples from patients achieving partial response (by RECISTv1.1). A higher percentage of subjects within the partial response group were more likely to maintain or increase resting NK cell infiltration on-treatment. PBMCs obtained prior to and on treatment showed no difference in CD56high and low NK profiles related to clinical benefit, highlighting that these changes in NK cell involvement are specific within tumor tissue. We sought to explore whether NK cells may be involved in DPX-based therapeutic efficacy using the HPV E7 model, C3, implanted in Rag1-/- mice, deficient in T and B cells. Mice were pre-treated with DPX packaged with the HPV E7 49-57 T cell peptide antigen (DPX-R9F) and 16 days later implanted with C3 tumor cells. At 40 days post treatment, 100% of control mice showed C3 tumor growth. By contrast, in the DPX-R9F immunized group, 60% of the mice were tumor free. Moreover, in the remaining 40% of the immunized group, the C3 tumors grew significantly slower than C3 tumors of the control group. Together, these data indicate that immunization with DPX-R9F enabled tumor control even in the absence of T or B cell function. To assess whether tumor control involved NK cells/perforin function, we repeated the experiment in Rag1-/-/Perforin-/- mice. In these mice, DPX-R9F immunization was far less effective than in the Rag1-/- mice, showing that only 20% of immunized mice were tumor free and suggesting that DPX-R9F mediated tumor control was partially dependent upon NK cell/perforin function. Taken together, these results from both clinical/translational studies and preclinical models suggest a distinct role for NK cells, in addition to the previously recognized role for T and B cells, in DPX-mediated immunotherapeutic efficacy. Citation Format: Moamen Bydoun, Daniel Medina-Luna, Brennan Dirk, Jeremy Graff, Olga Hrytsenko, Andrew Makrigiannis. NK cells are involved in promoting anti-tumor responses to DPX-peptide immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 623.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».