Grant Award Details
To enable a pre-IND meeting for Neural Stem cell-mediated oncolytic immunotherapy for ovarian cancer
Grant Application Details
- Neural Stem cell-mediated oncolytic immunotherapy for ovarian cancer
A clinically tested tumor-tropic neural stem cell (NSC) platform for effective distribution of oncolytic virotherapy to ovarian cancer metastases
Area of Impact
This NSC-delivered virotherapy approach will lead to a more efficacious, less toxic treatment for metastatic ovarian cancer and chemoresistent cells.
Mechanism of Action
CRAd-S-pk7 is a tumor specific replication-competent adenovirus driven by a survivin promoter, which is constitutively highly expressed in ovarian cancer cells. We will use our tumor-tropic/tumor-penetrating NSC platform to produce the oncolytic virus within IP ovarian metastases. Viral replication will lyse cancer cells and infect neighboring cancer cells, thus amplifying its effect until reaching normal tissue. We will also stimulate a secondary immune response to newly exposed tumor antigens.
Unmet Medical Need
Most ovarian cancer patients present late stage with abdominal metastases, and cant complete chemotherapy due to severe toxicity and chemoresistance. NSCs will more effectively target and distribute an oncolytic virus, selectively lysing cancer cells and stimulating an anti-tumor immune response.
Pre-IND meeting, ready for GMP clinical lot.
Major Proposed Activities
- In vivo determination of dosing regimen (multiple rounds) for maximal therapeutic efficacy
- In vivo determination of secondary immune response, following oncolysis of tumor cells
- In vivo determination of preliminary safety/tox profile
Ovarian cancer is the most lethal gynecologic malignancy, resulting in 1,500 deaths annually in California. At diagnosis, >70% of patients already have metastases throughout their abdomen, leading to a dismal 34% 5-year survival rate. We anticipate that our stem cell-delivered oncolytic virotherapy will lead to a more effective, less toxic treatment for these patients that will kill even metastatic tumor foci and chemoresistant cells, improving survival of ovarian cancer patients in California.
- Stem Cell Res Ther (2021) Allogeneic human neural stem cells for improved therapeutic delivery to peritoneal ovarian cancer. (PubMed: 33761999)
- Mol Ther Oncolytics (2020) Neural Stem Cells Improve the Delivery of Oncolytic Chimeric Orthopoxvirus in a Metastatic Ovarian Cancer Model. (PubMed: 32775617)
- Proc Natl Acad Sci U S A (2020) Specific targeting of ovarian tumor-associated macrophages by large, anionic nanoparticles. (PubMed: 32732430)
- Mol Ther Oncolytics (2019) Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer. (PubMed: 30719498)