Recombinant Virus to Block Anti-Tumor Immunosuppression

Description:

The current invention involves a recombinant myxoma virus which has been engineered to express the extracellular portion of the human PD1 protein from infected cells (vPD1). Soluble PD1 protein binds to the PDL1 on local tumor cells preventing PDL1 from engaging the inhibitory PD1 expressed on tumor infiltration T cells.

To date, the inventor has tested the virus as a treatment for subcutaneous melanoma in a preclinical mouse model and it produces ~60% long-term cures, a figure which is outstanding for this model (Fig 1). Moreover, vPD1 is more effective at eradicating melanoma than a Myxoma virus combined with a PD1 antibody (vGFP + αPD1), or a Myxoma virus alone measured by survival after 80 days (Fig 1A), average overall response rates (Fig 1B) and complete response rates (Fig 1C). The researchers also found that vPD1 outperforms Myxoma virus in a LLC lung cancer model. This virus should also be functional against any malignancy which is susceptible to myxoma virus and also expresses PDL1.

 

Overview: Myxoma virus is a rabbit specific poxvirus with established oncolytic potential against a variety of malignancies including myeloma, melanoma, glioblastoma, pancreatic cancer, and others. The virus is thought to exhibit antitumor effects through two distinct mechanisms. First, the virus directly infects and kills tumor cells. Second, viral infection of tumor cells induces a secondary anti-tumor immune response. While the combination of these mechanisms is effective at debulking primary tumors, it often fails to produce long-term cures due to immune inhibition within the tumor microenvironment. One of the major inhibitory pathways present in tumor microenvironments is the PD1-PDL1 checkpoint in which PDL1 expressed on tumor cells binds to PD1 on anti-tumor T cells resulting in T cell exhaustion. Current methods to overcome this pathway including systemic injection of antibodies which block the PD1-PDL1 interaction, however, these systemic treatments are costly, time consuming, and associated with low response rates and noticeable toxicities.

 

Applications: Cancer therapy

Advantages:  Recombinant virus prevents PDL1 from engaging inhibitory PD1 on tumor infiltration T cells

Key Words: Recombinant virus, myxoma, melanoma, cancer, myeloma, glioblastoma, pancreas, T cells, tumor, malignant, PD1

 

Publications: Bartee, et al. "Tumor-localized secretion of soluble PD1 enhances oncolytic virotherapy." (2017), 77(11): 2952-2963.

 

Background Publications: Tosic, Vesna, et al. "Myxoma Virus Expressing a Fusion Protein of Interleukin-15 (IL15) and IL15 Receptor Alpha Has Enhanced Antitumor Activity." (2014): e109801.

 

Stanford, Marianne M., et al. "Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo." Molecular Therapy 16.1 (2008): 52-59.

 

Inventors: Eric Bartee

Patent Status:  Provisional Application filed 06/07/2017

MUSC-FRD Technology ID: P1606

 

Patent Information:
Category(s):
Therapeutic
For Information, Contact:
Scott Davis
Sr Licensing Manager
MUSC Foundation for Research Development
843-876-1900
davissco@musc.edu
Inventors:
Eric Bartee
Keywords:
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