PD-1 inhibitor plus oncolytic vaccinia virus is a safe and effective treatment option for metastatic renal cell carcinoma
© 2024. The Author(s)..
BACKGROUND: Although a combination of immune checkpoint inhibitors (ICIs) is recommended as the first line treatment option for metastatic renal cell carcinoma (mRCC), several immune-related adverse events (irAEs) occur, especially hepatitis. We explored the therapeutic benefits and safety profile of combining oncolytic vaccinia virus, JX-594, with a programmed cell death protein-1 (PD-1) inhibitor.
METHODS: We used early-stage and advanced-stage orthotopic murine mRCC models developed by our group. PD-1 inhibitor monotherapy or a PD-1 inhibitor combined with either JX-594 or a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor were systemically injected through the peritoneum. An immunofluorescence analysis was performed to analyze the tumor immune microenvironment (TIME). irAEs were assessed in terms of hepatitis.
RESULTS: In the early-stage mRCC model mice, the combination of JX-594 and a PD-1 inhibitor significantly decreased the primary tumor size and number of lung nodules, compared with the ICI combination, but the JX-594 and PD-1 inhibitor combination and ICI combination did not differ significantly in the advanced-stage mRCC model mice. The JX-594 and PD-1 inhibitor combination induced tumor-suppressing TIME changes in both the early- and advanced-stage mRCC models. Furthermore, mice treated with the ICI combination had significantly greater hepatic injuries than those treated with the JX-594 and PD-1 inhibitor combination which was evaluated in early-stage mRCC model.
CONCLUSIONS: The JX-594 and PD-1 inhibitor combination effectively reduced primary tumors and the metastatic burden, similar to ICI combination therapy, through dynamic remodeling of the TIME. Furthermore, hepatitis was significantly decreased in the JX-594 and PD-1 inhibitor combination group, suggesting the potential benefit of that combination for reducing ICI-induced toxicity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
Cancer cell international - 24(2024), 1 vom: 30. Jan., Seite 50 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Park, Jee Soo [VerfasserIn] |
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| Links: |
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| Themen: |
Hepatitis |
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| Anmerkungen: |
Date Revised 02.02.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1186/s12935-024-03238-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: Although a combination of immune checkpoint inhibitors (ICIs) is recommended as the first line treatment option for metastatic renal cell carcinoma (mRCC), several immune-related adverse events (irAEs) occur, especially hepatitis. We explored the therapeutic benefits and safety profile of combining oncolytic vaccinia virus, JX-594, with a programmed cell death protein-1 (PD-1) inhibitor | ||
| 520 | |a METHODS: We used early-stage and advanced-stage orthotopic murine mRCC models developed by our group. PD-1 inhibitor monotherapy or a PD-1 inhibitor combined with either JX-594 or a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor were systemically injected through the peritoneum. An immunofluorescence analysis was performed to analyze the tumor immune microenvironment (TIME). irAEs were assessed in terms of hepatitis | ||
| 520 | |a RESULTS: In the early-stage mRCC model mice, the combination of JX-594 and a PD-1 inhibitor significantly decreased the primary tumor size and number of lung nodules, compared with the ICI combination, but the JX-594 and PD-1 inhibitor combination and ICI combination did not differ significantly in the advanced-stage mRCC model mice. The JX-594 and PD-1 inhibitor combination induced tumor-suppressing TIME changes in both the early- and advanced-stage mRCC models. Furthermore, mice treated with the ICI combination had significantly greater hepatic injuries than those treated with the JX-594 and PD-1 inhibitor combination which was evaluated in early-stage mRCC model | ||
| 520 | |a CONCLUSIONS: The JX-594 and PD-1 inhibitor combination effectively reduced primary tumors and the metastatic burden, similar to ICI combination therapy, through dynamic remodeling of the TIME. Furthermore, hepatitis was significantly decreased in the JX-594 and PD-1 inhibitor combination group, suggesting the potential benefit of that combination for reducing ICI-induced toxicity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hepatitis | |
| 650 | 4 | |a Immune-related adverse events | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Oncolytic viruses | |
| 650 | 4 | |a Renal cell carcinoma | |
| 700 | 1 | |a Lee, Myung Eun |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Jongchan |e verfasserin |4 aut | |
| 700 | 1 | |a Oh, Keunhee |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Namhee |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, Minsun |e verfasserin |4 aut | |
| 700 | 1 | |a Jang, Won Sik |e verfasserin |4 aut | |
| 700 | 1 | |a Ham, Won Sik |e verfasserin |4 aut | |
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