CCK Receptor and Immune Checkpoint Inhibition for Resistant PDAC
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), is resistant to standard chemotherapy and immunotherapy, leading to poor survival rates due to its inability to be diagnosed early and its relative resistance to these treatments.
Innovation Solution
Administering a cholecystokinin (CCK) receptor inhibitor in combination with an immune checkpoint inhibitor to alter the tumor microenvironment, increase immune cell infiltration, and enhance sensitivity to immunotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard chemotherapy is administered to pancreatic cancer patients, then treatment is provided, but the cancer shows relative resistance leading to poor survival rates
Solution Approach 1:
The patent combines CCK receptor inhibitor with immune checkpoint inhibitor to create a dual-mechanism treatment. The CCK receptor inhibitor alters the tumor microenvironment and increases immune cell infiltration, while the immune checkpoint inhibitor enhances immune response, together overcoming the resistance that single therapies cannot address
Solution Approach 2:
The CCK receptor inhibitor acts as an intermediary that modifies the tumor microenvironment to make it more susceptible to immunotherapy. By altering the microenvironment and increasing immune cell infiltration, it mediates between the immune system and the resistant cancer cells, enabling the immune checkpoint inhibitor to work effectively
2Reliability
If immunotherapy is administered to pancreatic cancer patients, then immune response is activated, but the cancer remains resistant due to microenvironment factors
Solution Approach 1:
The CCK receptor inhibitor is administered to preliminarily alter the tumor microenvironment and increase immune cell infiltration before the immune checkpoint inhibitor takes full effect. This preliminary modification of the microenvironment prepares the cancer tissue to be more responsive to subsequent immunotherapy
Solution Approach 2:
The CCK receptor inhibitor serves as a mediator that transforms the resistant tumor microenvironment into a more immunogenic state. It bridges the gap between the current microenvironment and the desired state for effective immunotherapy by increasing immune cell infiltration and altering microenvironmental factors
3Reliability
If combination therapy with CCK receptor inhibitor and immune checkpoint inhibitor is administered, then tumor growth is reduced and survival is improved, but treatment complexity increases
Solution Approach 1:
The patent merges two distinct therapeutic mechanisms into a single combination regimen. The CCK receptor inhibitor and immune checkpoint inhibitor work synergistically, with the former preparing the microenvironment and the latter activating the immune response, achieving improved survival through their combined action
Data Source
AI summary
Provided herein are methods for treating a cholecystokinin (CCK) receptor-expressing cancerous tumor in a subject. The methods comprising administering to the subject an effective amount of a CCK receptor inhibitor and an effective amount of an immune checkpoint inhibitor, wherein the CCK receptor inhibitor inhibits one or more CCK receptors selected from the group consisting of a CCK-A receptor, a CCK-B receptor and a CCK-C receptor, and wherein the immune checkpoint inhibitor is a programmed cell death protein 1 (PD1) inhibitor or a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor.