Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model
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...
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MDPI AG
2021-06-01
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| Online Access: | https://www.mdpi.com/1420-3049/26/12/3744 |
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| author | Ricardo G. Alvim Petrina Georgala Lucas Nogueira Alexander J. Somma Karan Nagar Jasmine Thomas Laura Alvim Amelia Riegel Christopher Hughes Jie Chen Augusto B. Reis Souhil Lebdai Avigdor Scherz Steven Zanganeh Rui Gardner Kwanghee Kim Jonathan A. Coleman |
| author_facet | Ricardo G. Alvim Petrina Georgala Lucas Nogueira Alexander J. Somma Karan Nagar Jasmine Thomas Laura Alvim Amelia Riegel Christopher Hughes Jie Chen Augusto B. Reis Souhil Lebdai Avigdor Scherz Steven Zanganeh Rui Gardner Kwanghee Kim Jonathan A. Coleman |
| author_sort | Ricardo G. Alvim |
| collection | DOAJ |
| description | 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. Experimental design: 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. |
| first_indexed | 2024-03-10T10:15:51Z |
| format | Article |
| id | doaj.art-b4d0e73603c74f719b706b1af1379c65 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:15:51Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b4d0e73603c74f719b706b1af1379c652023-11-22T00:50:59ZengMDPI AGMolecules1420-30492021-06-012612374410.3390/molecules26123744Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor ModelRicardo G. Alvim0Petrina Georgala1Lucas Nogueira2Alexander J. Somma3Karan Nagar4Jasmine Thomas5Laura Alvim6Amelia Riegel7Christopher Hughes8Jie Chen9Augusto B. Reis10Souhil Lebdai11Avigdor Scherz12Steven Zanganeh13Rui Gardner14Kwanghee Kim15Jonathan A. Coleman16Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Surgery, Federal University of Minas Gerais, Belo Horizonte 30130-100, BrazilUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Plants and Environmental Sciences, The Weizmann Institute of Science, Rehovot 76100, IsraelDepartment of Bioengineering, University of Massachusetts, Dartmouth, MA 02747, USAFlow Cytometry Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAPurpose: 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. Experimental design: 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.https://www.mdpi.com/1420-3049/26/12/3744bladder cancertumor ablationTOOKADfocal therapyimmunotherapy |
| spellingShingle | Ricardo G. Alvim Petrina Georgala Lucas Nogueira Alexander J. Somma Karan Nagar Jasmine Thomas Laura Alvim Amelia Riegel Christopher Hughes Jie Chen Augusto B. Reis Souhil Lebdai Avigdor Scherz Steven Zanganeh Rui Gardner Kwanghee Kim Jonathan A. Coleman Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model Molecules bladder cancer tumor ablation TOOKAD focal therapy immunotherapy |
| title | Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model |
| title_full | Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model |
| title_fullStr | Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model |
| title_full_unstemmed | Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model |
| title_short | Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model |
| title_sort | combined ox40 agonist and pd 1 inhibitor immunotherapy improves the efficacy of vascular targeted photodynamic therapy in a urothelial tumor model |
| topic | bladder cancer tumor ablation TOOKAD focal therapy immunotherapy |
| url | https://www.mdpi.com/1420-3049/26/12/3744 |
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