Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model.
Molecules
; 26(12)2021 06 19.
Article
de En
| MEDLINE
| ID: mdl-34205347
ABSTRACT
PURPOSE:
Vascular targeted photodynamic therapy (VTP) is a nonsurgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model. EXPERIMENTALDESIGN:
In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses.RESULTS:
The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and prolonged survival to a greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells.CONCLUSIONS:
Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs urologiques
/
Récepteur au OX40
/
Récepteur-1 de mort cellulaire programmée
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
/
Male
Langue:
En
Journal:
Molecules
Sujet du journal:
BIOLOGIA
Année:
2021
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique