Treating Cancer with a CCK Receptor Inhibitor and an Immune Checkpoint Inhibitor

Categories:  “Cancer Therapeutics“

Reference #: 2017-003

OTC Contact: Ruchika Nijhara, Ph.D., MBA, CLP (Directory Information | Send a Message)

Description

The invention is a combination therapy for the treatment of cancer, using cholecystokinin (CCK) receptor inhibitors in conjunction with immune checkpoint inhibitors.  CCK receptor antagonist such as proglumide has anti-cancer fibrotic properties that may improve the efficacy of immune check point antibodies. The invention has potential utility for the treatment of pancreatic cancer, which is resistant to chemotherapy and immunotherapy.

Murine models for pancreatic cancer have facilitated the study of premalignant lesions called pancreatic intraepithelial neoplasia (PanIN). PanIN plays a significant role in pancreatic carcinogenesis over time,however, the lesions alone do not transform normal cells into a cancerous ones, additional stimuli such as inflammation is required.

Georgetown University researchers validated CCK’s involvement in the malignant progression of PanIN. CCK was identified as an inflammation instigator, that when blocked by a receptor antagonist, lead toreduced inflammation and fibrosis, in turn leading to arrested PanIN development and progression in mice.

Applications

• Targeted therapy to cancers that express CCK receptors.
• Can be used to improve treatment of fibrotic cancers such as pancreatic, hepatocellular, gastric, colon and lung cancer

Advantages

• Targeted cancer therapy can be used in cancers that are resistant to chemotherapy and/or immunotherapy
• Can improve the efficacy of immune checkpoint antibodies
• Potential to elucidate CCK receptor’s diagnostic utility as an early stage cancer biomarker

Stage of Development

Validated in murine models. The clinical study to use the combination therapy using Proglumide with an immune checkpoint antibody to be initiated in the next few months.

Inventors

Jill P. Smith