Intrapleural interleukin-2-expressing oncolytic virotherapy enhances acute antitumor effects and T-cell receptor diversity in malignant pleural disease.
IL-2
PD-1
immunotherapy
intrapleural therapy
malignant pleural disease
malignant pleural effusion
metastatic lung cancer
oncolytic virotherapy
vaccinia virus
Journal
The Journal of thoracic and cardiovascular surgery
ISSN: 1097-685X
Titre abrégé: J Thorac Cardiovasc Surg
Pays: United States
ID NLM: 0376343
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
31
05
2020
revised:
15
10
2020
accepted:
11
11
2020
pubmed:
25
1
2021
medline:
23
3
2022
entrez:
24
1
2021
Statut:
ppublish
Résumé
The mainstay of treatment for patients with malignant pleural disease is fluid drainage and systemic therapy. A tumor-specific oncolytic virus or T-cell-activating interleukin-2 immunotherapy may provide an opportunity for local control. We previously developed a vaccinia virus-expressing interleukin-2, an oncolytic virus that mediated tumor regression in preclinical peritoneal tumor models with expansion of tumor-infiltrating lymphocytes. We evaluated the antitumor efficacy and immune modulatory effects of vaccinia virus-expressing interleukin-2 in malignant pleural disease. A murine model of malignant pleural disease was established with percutaneous intrapleural deposition of the Lewis lung carcinoma cell line and monitored with bioluminescent imaging. After intrapleural or systemic administration of vaccinia viruses (vaccinia virus yellow fluorescent protein control, vaccinia virus-expressing interleukin-2), systemic anti-programmed cell death-1 antibody, or combination therapy (vaccinia virus-expressing interleukin-2 and anti-programmed cell death-1), tumor mass, immune cell infiltration, T-cell receptor diversity, and survival were assessed. Intrapleural vaccinia virus resulted in significant tumor regression compared with phosphate-buffered saline control (P < .05). Inclusion of the interleukin-2 transgene further increased intratumoral CD8 Intrapleural vaccinia virus-expressing interleukin-2 reduced tumor burden and enhanced survival in a murine malignant pleural disease model. Increased CD8
Identifiants
pubmed: 33485667
pii: S0022-5223(20)33337-7
doi: 10.1016/j.jtcvs.2020.11.160
pmc: PMC9594625
mid: NIHMS1835651
pii:
doi:
Substances chimiques
Interleukin-2
0
Pdcd1 protein, mouse
0
Programmed Cell Death 1 Receptor
0
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e313-e328Subventions
Organisme : CSRD VA
ID : IK2 CX001771
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA229275
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA236965
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA206012
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM115366
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA160417
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI036211
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA113263
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Published by Elsevier Inc.
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