Targeted LNA Gapmer Therapy for Pancreatic Cancer

OVERVIEW

This invention presents a novel therapeutic approach for treating CCK-BR positive cancers, with a primary focus on pancreatic cancer. It features the use of Locked Nucleic Acid (LNA) Gapmers—antisense oligonucleotides (ASOs) designed to selectively downregulate gastrin mRNA, a key driver in pancreatic cancer growth. These LNA Gapmers are engineered for high stability and longevity in vivo, ensuring effective RNA interference. The technology incorporates a peptide or DNA aptamer that specifically targets the cholecystokinin-B receptor (CCK-BR), which is overexpressed in pancreatic cancer cells, thereby enhancing the specificity and efficacy of the treatment. Preclinical studies have demonstrated that this receptor-targeted LNA Gapmer significantly inhibits tumor growth and metastasis in animal models of human pancreatic cancer, offering a promising alternative to current chemotherapy treatments.

BACKGROUND

Pancreatic cancer is one of the most lethal malignancies, projected to become the second leading cause of cancer-related deaths within the next decade. Current treatment options are limited and largely ineffective, with chemotherapy being the only approved therapy for advanced stages. However, chemotherapy is associated with significant toxicity and poor response rates. This invention addresses the urgent need for more effective and targeted treatment strategies for pancreatic cancer, particularly for tumors that do not respond to existing immune-based therapies.

Benefit

Provides a targeted therapy that selectively attacks cancer cells, minimizing off-target effects.Demonstrates high stability and a long half-life, which enhances its effectiveness in vivo.Offers a less toxic alternative to chemotherapy, reducing the side effects associated with traditional treatments.Shows potential for application in other CCK-BR positive cancers, expanding the scope of its therapeutic impact.

Market Application

Treatment of advanced pancreatic cancer with a targeted, less toxic approach compared to traditional chemotherapy.Potential application in other CCK-BR positive cancers, such as colon, liver, gastric, esophageal, small cell lung, and medullary thyroid cancers.Could be integrated into personalized cancer therapy regimes, particularly for patients with CCK-BR positive tumors.Offers a new avenue for developing cancer treatments that leverage RNA interference technologies.

Publications

US Patent Application Filed

TARGET-SPECIFIC LNA GAPMERS DECREASE GROWTH AND METASTASES OF PANCREATIC CANCER, May 2024, 166(5):S-1332-S-1333, DOI:10.1016/S0016-5085(24)03508-X

LNA gapmer to gastrin inhibits growth and metastases of human pancreatic cancer in mice, March 2024, Cancer Research 84(6_Supplement):3250-3250, 84(6_Supplement):3250-3250, DOI:10.1158/1538-7445.AM2024-3250