Engineered Oncolytic Viruses for Targeted Cancer Cell Infection
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Solution Overview
Problem
Current cancer treatments, including surgery, radiation, chemotherapy, and immunotherapy, are often deployed late in cancer development and have undesirable side effects, and solid tumors pose challenges due to antigen heterogeneity and immune-suppressing agents like PD-L1, necessitating more effective and precise therapies.
Innovation Solution
Development of artificial oncolytic viruses engineered to selectively bind to cancer cells using highly expressed or preferentially expressed binding partners and regulatory regions, allowing for targeted infection and replication while minimizing impact on normal cells, potentially incorporating therapeutic agents, immune evasion mechanisms, and diagnostic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer treatments (surgery, radiation, chemotherapy, immunotherapy) are deployed, then cancer cells can be eradicated, but undesirable side effects occur and treatments are effective only when deployed late in cancer development
Solution Approach 1:
The oncolytic virus is engineered with cancer-specific targeting domains (e.g., integrin-binding RGD peptides, EGFR-targeting single-chain Fv antibodies) that enable selective recognition and infection of cancer cells while sparing normal cells. The viral genome expression is controlled by cancer-specific promoters (e.g., telomerase promoter hTERT, survivin promoter BIRC5) that are active only in malignant cells, ensuring localized therapeutic action and minimizing systemic side effects
Solution Approach 2:
The oncolytic virus acts as a biological intermediary that delivers therapeutic payloads (cytokines, immunomodulatory agents, suicide genes) directly to cancer cells. This mediator approach allows controlled release of therapeutic agents within the tumor microenvironment, achieving cancer cell eradication while protecting surrounding healthy tissues from direct exposure to toxic substances
2Reliability
If solid tumors are treated with conventional therapies, then cancer cells can be eradicated, but antigen heterogeneity and immune-suppressing agents like PD-L1 complicate targeting strategies
Solution Approach 1:
The oncolytic virus platform is designed with multi-functional capabilities: (1) direct oncolysis through viral replication in cancer cells, (2) immunomodulation via expression of cytokines (IL-12, IL-18, GM-CSF) and immune checkpoint inhibitors (anti-PD-L1, anti-CTLA-4), (3) delivery of suicide genes (HSV-thymidine kinase, cytosine deaminase), and (4) targeting of multiple cancer types through interchangeable binding domains. This universal platform can adapt to different tumor types and heterogeneity patterns
3Reliability
If oncolytic viruses are engineered to selectively bind to cancer cells, then targeted infection and replication is achieved, but the complexity of virus engineering increases
Solution Approach 1:
The oncolytic virus is constructed as a modular platform with distinct functional segments: (1) targeting domain (integrin-binding RGD, EGFR-scFv, HER2-scFv), (2) viral genome with cancer-specific promoter-driven expression, (3) therapeutic payload (cytokines, immunomodulators, suicide genes), and (4) immune evasion mechanisms. This segmentation allows independent optimization and swapping of modules to address different cancer types while using a standardized viral backbone
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The engineered viruses induce targeted cell death in cancer cells, reducing tumor size and growth, with the potential for enhanced safety and efficacy by selectively infecting and replicating within cancer cells, thereby addressing the limitations of existing treatments.
Implementation Method 1
a domain engineered to selectively bind to a target cell via a binding partner identified as highly expressed or preferentially expressed on the target cell
Implementation Method 2
expression of the viral genome is engineered to be under the control of a regulatory region of a gene identified as highly expressed or preferentially expressed by the target cell
Implementation Method 3
artificial oncolytic viruses... induce targeted cell death in cancer cells, reducing tumor size and growth
Data Source
AI summary
The disclosure provides artificial viral compositions for use in treating cancer or a hyperproliferative disorder in a subject to whom the compositions are administered, as well as to methods of making and using the compositions.