Fusogenic oncolytic vaccinia virus enhances systemic antitumor immune response by modulating the tumor microenvironment

Nakatake, Motomu; Kuwano, Nozomi; Kaitsurumaru, Emi; Kurosaki, Hajime; Nakamura, Takafumi

doi:10.1016/j.ymthe.2020.12.024

Cited by 15 publications

(13 citation statements)

References 37 publications

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“…However, it fails to develop oncolytic viruselicited antitumor immune responses, which play a critical role in the efficacy of oncolytic virotherapy. Our previous studies demonstrated that VGF and O1-deleted oncolytic VVs elicited potent antitumor effects via systemic antitumor activity rather than local viral oncolytic activity in syngeneic tumor mouse models using melanoma, colon, and lung carcinomas, and its antitumor effects were enhanced by arming VV with the expression of IL-12 and IL-7 [51] or induction of cell-cell fusion [52]. Thus, it is worth evaluating the combinational effects of armed MDRVV and 5-FC in syngenic mouse tumor models in the future.…”

Section: Discussionmentioning

confidence: 99%

Anti-Tumor Effects of MAPK-Dependent Tumor-Selective Oncolytic Vaccinia Virus Armed with CD/UPRT against Pancreatic Ductal Adenocarcinoma in Mice

Kurosaki

Nakatake

Sakamoto

et al. 2021

Cells

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Engineered vaccinia virus serves as an oncolytic virus for cancer virotherapy. We evaluated the oncolytic characteristics of VGF- and O1-deleted recombinant mitogen-activated protein kinase (MAPK)-dependent vaccinia virus (MDRVV). We found that compared with viruses with the deletion of either gene alone, MDRVV is more attenuated in normal cells and can replicate in cancer cells that exhibit constitutive ERK1/2 activation in the MAPK pathway. We armed MDRVV with a bifunctional fusion gene encoding cytosine deaminase and uracil phosphoribosyltransferase (CD/UPRT), which converts 5-fluorocytosine (5-FC) into chemotherapeutic agents, and evaluated its oncolytic activity alone or in combination with 5-FC in human pancreatic cancer cell lines, tumor mouse models of peritoneal dissemination and liver metastasis, and ex vivo-infected live pancreatic cancer patient-derived tissues. CD/UPRT-armed MDRVV alone could efficiently eliminate pancreatic cancers, and its antitumor effects were partially enhanced in combination with 5-FC in vitro and in vivo. Moreover, the replication of MDRVV was detected in tumor cells of patient-derived, surgically resected tissues, which showed enlarged nuclei and high expression of pERK1/2 and Ki-67, and not in stromal cells. Our findings suggest that systemic injections of CD/UPRT-armed MDRVV alone or in combination with 5-FC are promising therapeutic strategies for pancreatic ductal adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Anti-Tumor Effects of MAPK-Dependent Tumor-Selective Oncolytic Vaccinia Virus Armed with CD/UPRT against Pancreatic Ductal Adenocarcinoma in Mice

Kurosaki

Nakatake

Sakamoto

et al. 2021

Cells

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“…FUVAC showed antitumor effect in a CD8+ T-cell-dependent manner and also inhibited infiltration of tumor-associated immune suppressive cells. 36 These results suggested that cell fusion is involved in oncolytic and antitumor effect of VV. A34 R is an EV glycoprotein of VV and involved in cell-to-cell transmission.…”

Section: Preclinical Investigation Of Oncolytic Vv In Crcmentioning

confidence: 91%

“… Immune checkpoint inhibitor i.t. 36 VVs Western reserve Deletion in N1 L, K1 L, K3 L, A46 R, or A52 R ΔK1 L VV, ΔA46 R VV, and ΔA52 R VV demonstrated improved antitumor effect and survival compared to vvDD. i.p.…”

Section: Preclinical Investigation Of Oncolytic Vv In Crcmentioning

confidence: 99%

The employment of vaccinia virus for colorectal cancer treatment: A review of preclinical and clinical studies

Qiaoyun

Zheng

Chen

et al. 2022

Human Vaccines & Immunotherapeutics

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Colorectal cancer (CRC) is one of the leading malignancies that causes death worldwide. Cancer vaccines and oncolytic immunotherapy bring new hope for patients with advanced CRC. The capability of vaccinia virus (VV) in carrying foreign genes as antigens or immunostimulatory factors has been demonstrated in animal models. VV of Wyeth, Western Reserve, Lister, Tian Tan, and Copenhagen strains have been engineered for the induction of antitumor response in multiple cancers. This paper summarized the preclinical and clinical application and development of VV serving as cancer vaccines and oncolytic vectors in CRC treatment. Additionally, the remaining challenges and future direction are also discussed.

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“…FUVAC exhibited improved direct oncolytic activity and indirect anti-tumor immunity. FUVAC was reported to significantly inhibit tumor growth and improve the tumor immune microenvironment by reducing the tumor-associated immune suppressive cells, such as Treg cells, TAMs, and M-MDSCs, and increasing cytotoxic CD8+ T cells systemically [71]. In another study, VV was demonstrated to infect tumor infiltrating Tregs, leading to the depletion of viral-mediated Tregs, which is required for tumor regression [72].…”

Section: Vaccinia Virus For the Modulation Of Tumor Microenvironmentmentioning

confidence: 99%

Oncolytic Vaccinia Virus in Lung Cancer Vaccines

Truong

Yoo

2022

Vaccines

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Therapeutic cancer vaccines represent a promising therapeutic modality via the induction of long-term immune response and reduction in adverse effects by specifically targeting tumor-associated antigens. Oncolytic virus, especially vaccinia virus (VV) is a promising cancer treatment option for effective cancer immunotherapy and thus can also be utilized in cancer vaccines. Non-small cell lung cancer (NSCLC) is likely to respond to immunotherapy, such as immune checkpoint inhibitors or cancer vaccines, since it has a high tumor mutational burden. In this review, we will summarize recent applications of VV in lung cancer treatment and discuss the potential and direction of VV-based therapeutic vaccines.

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Fusogenic oncolytic vaccinia virus enhances systemic antitumor immune response by modulating the tumor microenvironment

Cited by 15 publications

References 37 publications

Anti-Tumor Effects of MAPK-Dependent Tumor-Selective Oncolytic Vaccinia Virus Armed with CD/UPRT against Pancreatic Ductal Adenocarcinoma in Mice

Anti-Tumor Effects of MAPK-Dependent Tumor-Selective Oncolytic Vaccinia Virus Armed with CD/UPRT against Pancreatic Ductal Adenocarcinoma in Mice

The employment of vaccinia virus for colorectal cancer treatment: A review of preclinical and clinical studies

Oncolytic Vaccinia Virus in Lung Cancer Vaccines

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