Immune Effects of M51R Vesicular Stomatitis Virus Treatment of Carcinomatosis From Colon Cancer

Day, Gwenyth; Bryan, Michelle; Northrup, Scott; Lyles, Douglas S.; Westcott, Marlena M.; Stewart, John H.

doi:10.1016/j.jss.2019.07.032

Cited by 14 publications

(9 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treatment with M51R VSV inhibited tumor growth, improved survival, signi cantly increased the number of CD4 + T and B1b cells, and decreased myeloid-derived suppressor cells (MDSCs) in a murine model of peritoneal surface dissemination from colon cancer. (9). These ndings demonstrated that M51R VSV is a promising oncoimmunotherapy for colon cancer.…”

Section: Introductionmentioning

confidence: 78%

Treatment with M51R Vesicular Stomatitis Virus Induces Clonal Antitumor CD8+ T Cell Expansion in Colon Cancer

Godoy-Calderon

Gauchat

Stewart

2023

Preprint

Self Cite

View full text Add to dashboard Cite

Developing new and effective treatments for patients with metastatic colorectal cancer is crucial, as this condition is the fourth leading cause of cancer-related deaths. The potential of the M51R vesicular stomatitis virus (M51R VSV) as an oncolytic virus for various malignancies, including colorectal cancer, is being explored by our group and others. However, the immune response to this treatment is poorly understood. To address this knowledge gap, we conducted a study using a syngeneic murine model of colorectal cancer by administering M51R VSV at two doses and analyzing the resulting immune response. We found that both doses of M51R VSV induced a robust immune response, with overexpression of genes associated with NK cell function, antigen processing and presentation, and CD8+ T cell phenotype and function. CyTOF analysis showed an increased CD8+ T cell frequency and decreased G-MDSCs and FoxP3+CD25- Treg cells. TCR sequence analysis revealed clonal expansion of a-CT26 CD8+ T cells targeted against tumor-associated antigens, making combination therapy with CAR T cells a promising approach. Our work also suggests that combination therapy with M51R VSV and immune checkpoint inhibitors may be beneficial. These findings provide a strong foundation for advancing M51R VSV-based therapies for metastatic colorectal cancer in a population of patients with limited immunotherapeutic options.

show abstract

Section: Introductionmentioning

confidence: 78%

Treatment with M51R Vesicular Stomatitis Virus Induces Clonal Antitumor CD8+ T Cell Expansion in Colon Cancer

Godoy-Calderon

Gauchat

Stewart

2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…KUN-based expression of the granulocyte macrophage-colony stimulating factor (GM-CSF) resulted in cure in more than 50% of CT26 colon tumor-bearing mice [ 113 ]. In another approach, the oncolytic VSV(M51R) strain was administered intraperitoneally into BALB/c mice carrying luciferase-expressing CT26 tumors, which resulted in eradication of tumors demonstrated by reduced luciferase expression and prolonged survival of mice [ 114 ]. M1 alphavirus particles encapsulated in liposomes (M-LPO) were able to inhibit the growth of colorectal LoVo and liver Hep3B cancer cells [ 115 ].…”

Section: Gene Therapy Applicationsmentioning

confidence: 99%

Viral Vectors in Gene Therapy: Where Do We Stand in 2023?

Lundström¹

2023

Viruses

View full text Add to dashboard Cite

Viral vectors have been used for a broad spectrum of gene therapy for both acute and chronic diseases. In the context of cancer gene therapy, viral vectors expressing anti-tumor, toxic, suicide and immunostimulatory genes, such as cytokines and chemokines, have been applied. Oncolytic viruses, which specifically replicate in and kill tumor cells, have provided tumor eradication, and even cure of cancers in animal models. In a broader meaning, vaccine development against infectious diseases and various cancers has been considered as a type of gene therapy. Especially in the case of COVID-19 vaccines, adenovirus-based vaccines such as ChAdOx1 nCoV-19 and Ad26.COV2.S have demonstrated excellent safety and vaccine efficacy in clinical trials, leading to Emergency Use Authorization in many countries. Viral vectors have shown great promise in the treatment of chronic diseases such as severe combined immunodeficiency (SCID), muscular dystrophy, hemophilia, β-thalassemia, and sickle cell disease (SCD). Proof-of-concept has been established in preclinical studies in various animal models. Clinical gene therapy trials have confirmed good safety, tolerability, and therapeutic efficacy. Viral-based drugs have been approved for cancer, hematological, metabolic, neurological, and ophthalmological diseases as well as for vaccines. For example, the adenovirus-based drug Gendicine® for non-small-cell lung cancer, the reovirus-based drug Reolysin® for ovarian cancer, the oncolytic HSV T-VEC for melanoma, lentivirus-based treatment of ADA-SCID disease, and the rhabdovirus-based vaccine Ervebo against Ebola virus disease have been approved for human use.

show abstract

“…The oncolytic VSV(M51R)-LacZ vector with a mutation in the matrix (M) protein was evaluated for intravenous administration in BALB/c mice carrying 4T1 mammary tumors, which resulted in infection of multiple breast cancer lesions but no cytotoxicity in normal cells [ 65 ]. In another study, intraperitoneal administration of VSV(M51R) into BALB/c mice with luciferase-expressing CT-26 tumors reduced luciferase expression and prolonged survival [ 66 ]. Moreover, administration of the chimeric VSV-GP vector expressing the glycoprotein (GP) from the lymphocytic choriomeningitis virus (LCMV) showed replication in tumor cells, tumor-to-tumor spread of the virus, and widespread killing of tumor cells in nude mice with subcutaneous LLC1 lung tumors [ 67 ].…”

Section: Preclinical Studies Using Oncolytic Self-replicating Rna Vir...mentioning

confidence: 99%

Therapeutic Applications for Oncolytic Self-Replicating RNA Viruses

Lundström¹

2022

IJMS

View full text Add to dashboard Cite

Self-replicating RNA viruses have become attractive delivery vehicles for therapeutic applications. They are easy to handle, can be rapidly produced in large quantities, and can be delivered as recombinant viral particles, naked or nanoparticle-encapsulated RNA, or plasmid DNA-based vectors. The self-replication of RNA in infected host cells provides the means for generating much higher transgene expression levels and the possibility to apply substantially reduced amounts of RNA to achieve similar expression levels or immune responses compared to conventional synthetic mRNA. Alphaviruses and flaviviruses, possessing a single-stranded RNA genome of positive polarity, as well as measles viruses and rhabdoviruses with a negative-stranded RNA genome, have frequently been utilized for therapeutic applications. Both naturally and engineered oncolytic self-replicating RNA viruses providing specific replication in tumor cells have been evaluated for cancer therapy. Therapeutic efficacy has been demonstrated in animal models. Furthermore, the safe application of oncolytic viruses has been confirmed in clinical trials. Multiple myeloma patients treated with an oncolytic measles virus (MV-NIS) resulted in increased T-cell responses against the measles virus and several tumor-associated antigen responses and complete remission in one patient. Furthermore, MV-CEA administration to patients with ovarian cancer resulted in a stable disease and more than doubled the median overall survival.

show abstract

Immune Effects of M51R Vesicular Stomatitis Virus Treatment of Carcinomatosis From Colon Cancer

Cited by 14 publications

References 41 publications

Treatment with M51R Vesicular Stomatitis Virus Induces Clonal Antitumor CD8+ T Cell Expansion in Colon Cancer

Treatment with M51R Vesicular Stomatitis Virus Induces Clonal Antitumor CD8+ T Cell Expansion in Colon Cancer

Viral Vectors in Gene Therapy: Where Do We Stand in 2023?

Therapeutic Applications for Oncolytic Self-Replicating RNA Viruses

Contact Info

Product

Resources

About