Description:
Researchers from UTHealth and Ohio State University College of Medicine have collaborated to investigate the impact of oHSV therapy in combination with platinum agents using platinum-resistant high-grade serous ovarian carcinoma (HGSOC) as well as platinum-resistant ovarian clear cell carcinoma models. More importantly, they have developed a novel method of treating platinum-resistant ovarian cancers by co-administering an effective amount of oHSV together with a DNA damaging agent (e.g., cisplatin).
Background
Ovarian cancer has the highest case-fatality ratio of any gynecologic cancer. Although first-line chemotherapy for the treatment of ovarian cancer using platinum-based drugs (e.g., cisplatin) yields a response rate of >80%, a majority of patients eventually suffer from recurrence, with recurrent ovarian cancer being resistant to platinum-based therapy. Thus, improved therapeutic strategies to treat platinum-resistant ovarian cancers are urgently needed.
Discovery
Researchers have found the phenomenon of sensitization of cancer cells to immunotherapy via changes in cell signaling pathways when treated with both oHSV and cisplatin. Their study has revealed that oHSV infection can change the expression of cellular transporters ATP11B and ATP7B, thus increasing cisplatin retention and cisplatin-DNA adducts. The consequential increased DNA damage results in activation of innate immunity, which sensitizes tumors to immunotherapy. To go one step further, the investigators have developed a novel method of anti-cancer therapy comprising co-administration of an effective amount of oHSV together with a DNA damaging agent (e.g., cisplatin).
Benefits/Technology Advantages
- Cancer cells treated with both oHSV and cisplatin show increased DNA adducts, leading to activation of anti-tumor immunity via the STING pathway, and thereby resulting in the killing of tumor cells
- Combination therapy of oHSV and cisplatin can be used in the treatment of cancers, for example, certain types of ovarian cancers that have failed to respond adequately to conventional platinum-based therapy
Potential Applications
- Use it as a promising anti-cancer therapy, especially for the treatment of platinum-resistant ovarian cancers
- Can be developed into improved cancer therapeutic strategies in combination with further anti-cancer therapy, e.g. chemotherapy, radiotherapy, immunotherapy, or surgery
Intellectual Property Status
- US patent application filed: US17/066,162
- Available for licensing
Stage of Development
Pre-clinical
Associated Publications
Clin Cancer Res. 2021 Jan 15; 27(2): 542-553. DOI: 10.1158/1078-0432.CCR-20-2210
About the Principal Investigators
UTHealth Ref. No.: 2020-0007