Tumour-Selective CO Conjugates for Local Cancer Immunomodulation
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Solution Overview
Problem
Existing immunotherapies for cancer are not effective in all patients and do not yield complete or durable clinical responses, and the role of carbon monoxide (CO) in cancer immunity is not fully understood, necessitating a need for controlled and specific delivery of CO to target tumour tissues to reduce immunosuppression.
Innovation Solution
Development of CO releasing-conjugates comprising tumour-selective ligands, such as human serum albumin, that selectively accumulate in tumour tissue, releasing CO to downregulate immune checkpoint molecules and reduce tumour-associated macrophages, thereby reducing immunosuppression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CO-releasing molecules are used to treat cancer, then anti-tumour effects are observed, but CO may release in circulation causing toxicity
Solution Approach 1:
The patent uses tumour-selective ligands as intermediaries to deliver CO-releasing molecules specifically to tumour tissues. The ligand acts as a mediator that binds to the CORM and directs it to the tumour site through selective accumulation, preventing premature CO release in circulation while ensuring therapeutic CO delivery at the target site.
Solution Approach 2:
The patent creates local selectivity by conjugating CORMs with tumour-selective ligands that accumulate specifically in tumour tissue. This ensures that CO is released locally at the tumour site rather than systemically, achieving high local concentration for therapeutic effect while maintaining low systemic concentration to avoid toxicity.
2Reliability
If conventional immunotherapies are used, then immune response is activated, but they do not yield complete or durable clinical responses
Solution Approach 1:
The patent converts the immunosuppressive tumour microenvironment, which normally protects cancer cells, into a therapeutic target. By delivering CO specifically to tumour tissue, the treatment exploits the tumour's own immunosuppressive properties to concentrate the therapeutic agent where it is most needed, while simultaneously reversing the immunosuppression to enhance immune-mediated tumour destruction.
3Quantity of substance
If CORMs are administered systemically, then higher therapeutic doses can be given, but CO release in circulation occurs causing poisoning
Solution Approach 1:
The patent achieves local quality by creating tumour-targeted CORM conjugates that selectively accumulate in tumour tissue. This allows administration of higher doses of CO-releasing molecules because the CO is released primarily at the tumour site rather than throughout the circulation, maintaining a favourable therapeutic index.
Data Source
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AI summary
The present invention in various aspects and embodiments involves the use of CO releasing molecules, such as conjugates comprising tumour-selective ligands and groups capable of releasing carbon monoxide (CO), for exerting immunomodulatory effects in cancer treatment, such as reductions in the expression of immune checkpoint molecules and the level of inhibitory macrophages. This can reduce immunosuppression in tumour tissue and can be useful, for example, in the treatment of immunosuppressive cancers or the treatment of cancers in combination with cancer immunotherapy.