Neural Stem Cell Delivery of Oncolytic Viruses for Brain Cancer
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Solution Overview
Problem
Current treatments for ovarian and brain cancers, particularly those that have metastasized or developed drug resistance, face challenges such as poor viral penetration into tumors, immune system neutralization of oncolytic viruses, and severe side effects from chemotherapy, leading to limited efficacy and quality of life issues for patients.
Innovation Solution
The use of neural stem cells (NSCs) to deliver oncolytic adenoviruses, specifically conditionally replicating adenoviruses (CRAds) engineered to target tumor cells, combined with immune checkpoint inhibitors, to enhance viral delivery and immune response against cancer cells, while minimizing toxicity and autoimmunity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If oncolytic viruses are administered to treat cancer, then cancer cell death is induced irrespective of radio- or chemo-resistance, but poor viral penetration in tumors and poor viral spread through tumor-associated stroma and the tumor microenvironment limits efficacy
Solution Approach 1:
The patent uses neural stem cells as intermediary carriers to deliver oncolytic viruses to tumor sites. The NSCs migrate toward tumors and release the viruses locally, overcoming the limitation of poor viral penetration through the tumor microenvironment and stroma.
Solution Approach 2:
The neural stem cells are pre-loaded with oncolytic viruses before administration. This preliminary loading ensures that the viruses are delivered directly to the tumor site via NSC migration, bypassing the need for direct viral injection and improving penetration into difficult-to-reach tumor regions.
2Reliability
If standard chemotherapy is used to treat ovarian cancer, then some cancer cell death is achieved, but severe toxic side effects such as abdominal pain, nausea, and vomiting cause most patients to be unable to complete treatment cycles
Solution Approach 1:
The patent uses neural stem cells as targeted delivery vehicles to transport oncolytic viruses specifically to tumor sites. This targeted delivery spares healthy tissues from viral exposure and eliminates the severe systemic toxicities associated with traditional chemotherapy, while still achieving effective cancer cell death at the tumor location.
Solution Approach 2:
The therapeutic effect is localized to the tumor site through NSC-mediated viral delivery. The oncolytic viruses are released specifically where tumors are present, creating a localized therapeutic action that avoids the systemic toxicities of conventional chemotherapy while maintaining effective cancer cell killing at the target site.
3Reliability
If oncolytic viruses are administered to induce cancer cell lysis and immune response, then secondary immune responses are expected to be induced, but immune system neutralization of oncolytic viruses limits their effectiveness
Solution Approach 1:
The neural stem cells serve as protective carriers that shield the oncolytic viruses from immune system neutralization during delivery. The NSCs migrate to tumor sites and release the viruses locally, protecting them from circulating neutralizing antibodies and immune cells, thereby enabling effective immune response induction against the tumor.
Solution Approach 2:
The oncolytic viruses are pre-loaded into neural stem cells before administration, creating a protected delivery system. This preliminary encapsulation prevents immune system neutralization during transit and delivery, allowing the viruses to reach the tumor site intact and subsequently induce the desired secondary immune responses against cancer cells.
Data Source
AI summary
Provided are methods and compositions for treating cancer with a combination of neural stem cells (NSCs) and an oncolytic virus or a combination of oncolytic virotherapy and immune modulation. The method entails administrating to a subject a pharmaceutical composition comprising a combination of NSCs and an oncolytic virus, and/or NSCs packaged with one or more immunomodulatory viruses expressing one or more immunity checkpoint inhibitors, including adaptive immunity checkpoint inhibitors and innate immunity checkpoint inhibitors. The immunity checkpoint inhibitors include shRNAs against the immunity checkpoint proteins. The cancer includes but is not limited to primary, recurrent, and metastatic brain cancer, breast cancer, head and neck cancer, bladder cancer, ovarian cancer, uterine cancer, prostate cancer, skin cancer, lung cancer, and colorectal cancer.