scholarly journals Intravenous delivery of oncolytic vaccinia virus sensitizes pancreatic neuroendocrine tumors and metastases to immune checkpoint blockade

2021 ◽  
Author(s):  
Mitsuko Inoue ◽  
Minah Kim ◽  
Tomoyoshi Inoue ◽  
Madeline Tait ◽  
Thomas Byrne ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Neuroendocrine Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Pancreatic Neuroendocrine Tumors

Intratumoral expression of IL-7 and IL-12 using an oncolytic virus increases systemic sensitivity to immune checkpoint blockade

2020 ◽  
Vol 12 (526) ◽  
pp. eaax7992 ◽  
Author(s):  
Shinsuke Nakao ◽  
Yukinori Arai ◽  
Mamoru Tasaki ◽  
Midori Yamashita ◽  
Ryuji Murakami ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Vaccinia Virus ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Status ◽  
Tumor Regression ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Complete Tumor Regression ◽  
Complete Tumor

The immune status of the tumor microenvironment is a key indicator in determining the antitumor effectiveness of immunotherapies. Data support the role of activation and expansion of tumor-infiltrating lymphocytes (TILs) in increasing the benefit of immunotherapies in patients with solid tumors. We found that intratumoral injection of a tumor-selective oncolytic vaccinia virus encoding interleukin-7 (IL-7) and IL-12 into tumor-bearing immunocompetent mice activated the inflammatory immune status of previously poorly immunogenic tumors and resulted in complete tumor regression, even in distant tumor deposits. Mice achieving complete tumor regression resisted rechallenge with the same tumor cells, suggesting establishment of long-term tumor-specific immune memory. Combining this virotherapy with anti–programmed cell death-1 (PD-1) or anti–cytotoxic T lymphocyte antigen 4 (CTLA4) antibody further increased the antitumor activity as compared to virotherapy alone, in tumor models unresponsive to either of the checkpoint inhibitor monotherapies. These findings suggest that administration of an oncolytic vaccinia virus carrying genes encoding for IL-7 and IL-12 has antitumor activity in both directly injected and distant noninjected tumors through immune status changes rendering tumors sensitive to immune checkpoint blockade. The benefit of intratumoral IL-7 and IL-12 expression was also observed in humanized mice bearing human cancer cells. These data support further investigation in patients with non-inflamed solid tumors.

Analysis of Advanced Melanomas Changed from Immune Checkpoint Blockade Therapy to Palliative Care

2018 ◽  
Vol 80 (1) ◽  
pp. 51-55
Author(s):  
Ai KAJITA ◽  
Osamu YAMASAKI ◽  
Tatsuya KAJI ◽  
Hiroshi UMEMURA ◽  
Keiji IWATSUKI
Keyword(s):  
Palliative Care ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

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