Method for Generation of Tumor-Adapted Oncolytic Viruses

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This invention provides a rapid method for generating oncolytic (cancer-killing) RNA viruses that are specially adapted to overcome resistance in an individual patient’s tumor cells. Rather than using lengthy conventional evolutionary methods that require many rounds of viral passage to select adapted viruses, this method accelerates the process by identifying beneficial mutations in the virus population early (after just a few passages). These mutations are then integrated into a new viral genome using molecular cloning, allowing the production of a personalized and highly effective oncolytic virus for cancer therapy. The approach is particularly demonstrated for coxsackievirus B3 adaptations for colorectal cancer.

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• Personalized cancer treatment by producing patient-specific oncolytic viruses to target their resistant tumor cells.
• Overcoming resistance in tumor types that are refractory to standard oncolytic virotherapy.
• Rapid generation of improved oncolytic viruses for use in clinical trials and research.
• Development of safer and more selective oncolytic viruses by incorporating tissue-specific control elements.
• Treatment of colorectal cancer and potentially other solid tumors with similar characteristics.
• Production of stable cDNA clones for pharmaceutical manufacturing of therapeutic viruses.

BenefitsContent extracted from patent full text and abstract with AI.

• Dramatically reduces the time required to generate personalized and adapted oncolytic viruses for patients, making tailored therapies feasible even for those with short prognoses.
• Can overcome tumor cell resistance where existing oncolytic virus therapies fail.
• Combines multiple beneficial mutations quickly, enhancing virus efficacy (greater tumor lysis and replication in target cells).
• Allows for targeted and safer therapy by enabling the inclusion of elements that restrict viral replication to tumor tissue, reducing side effects.
• The method produces stable cDNA clones that are easy to store, propagate, and utilize for virus production as needed.
• Applicable to various RNA (and potentially DNA) oncolytic viruses and a wide range of cancer types.
• Opens the possibility for more rapid development and approval of new oncolytic virus therapies.

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Patent Abstract

The present invention relates to a method for generating personalized oncolytic RNA viruses, improving known oncolytic RNA viruses, or circumventing the resistance of tumor cells against such RNA viruses. The method comprises performing of a minimalistic number of passages in e.g. a tumor cell line or in patient tissue extracted from a tumor and then identifying mutations occurred during the early passages. The method further comprises the generation of a cDNA clone comprising at least one, most or all mutations identified and propagating a correspondent oncolytic RNA virus, which carries at least one, most or all mutations of the RNA virus adapted in the method for use in a tumor treatment.