Unknown

Dataset Information

0

Superagonist IL-15-Armed Oncolytic Virus Elicits Potent Antitumor Immunity and Therapy That Are Enhanced with PD-1 Blockade.


ABSTRACT: Oncolytic immunotherapy is a promising novel therapeutic for cancer, and further preclinical studies may maximize its therapeutic efficacy. In this study, we construct a novel oncolytic vaccinia virus (VV) expressing a superagoinst IL-15, a fusion protein of IL-15 and IL-15Ralpha. This virus, named vvDD-IL15-R?, possesses similar replication efficiency as the parental virus vvDD yet leads to significantly more regression of the disease and extends the survival of mice bearing MC38 colon or ID8 ovarian cancer. This novel virus elicits potent adaptive antitumor immunity as shown by ELISPOT assays for interferon-gamma-secreting CD8+ T cells and by the rejection of tumor implants upon re-challenge in the mice, which were previously cured by vvDD-IL15-R? treatment. In vivo cell depletion assays with antibodies showed that this antitumor activity is highly dependent on CD8+ T cells but much less so on CD4+ T cells and NK cells. Finally, the combination of the oncolytic immunotherapy with anti-PD-1 antibody dramatically improves the therapeutic outcome compared to either anti-PD-1 alone or vvDD-IL15-R? alone. These results demonstrate that the IL-15-IL-15R? fusion protein-expressing OV elicits potent antitumor immunity, and rational combination with PD-1 blockade leads to dramatic tumor regression and prolongs the survival of mice bearing colon or ovarian cancers.

SUBMITTER: Kowalsky SJ 

PROVIDER: S-EPMC6171074 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Superagonist IL-15-Armed Oncolytic Virus Elicits Potent Antitumor Immunity and Therapy That Are Enhanced with PD-1 Blockade.

Kowalsky Stacy J SJ   Liu Zuqiang Z   Feist Mathilde M   Berkey Sara E SE   Ma Congrong C   Ravindranathan Roshni R   Dai Enyong E   Roy Edward J EJ   Guo Zong Sheng ZS   Bartlett David L DL  

Molecular therapy : the journal of the American Society of Gene Therapy 20180717 10


Oncolytic immunotherapy is a promising novel therapeutic for cancer, and further preclinical studies may maximize its therapeutic efficacy. In this study, we construct a novel oncolytic vaccinia virus (VV) expressing a superagoinst IL-15, a fusion protein of IL-15 and IL-15Ralpha. This virus, named vvDD-IL15-Rα, possesses similar replication efficiency as the parental virus vvDD yet leads to significantly more regression of the disease and extends the survival of mice bearing MC38 colon or ID8 o  ...[more]

Similar Datasets

| S-EPMC4839379 | biostudies-literature
| S-EPMC9840182 | biostudies-literature
| S-EPMC8360872 | biostudies-literature
| S-EPMC4146345 | biostudies-literature
| S-EPMC9663162 | biostudies-literature
| S-EPMC7272274 | biostudies-literature
| S-EPMC9633566 | biostudies-literature
| S-EPMC10546667 | biostudies-literature
| S-EPMC6858551 | biostudies-literature
| S-EPMC6667823 | biostudies-other