FRRB Project 1751658 - Leveraging gene-based tools to control local and systemic circuits of tumor tolerance
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Name and Surname of PI |
Mario Leonardo Squadrito |
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Project Acronym |
GenTooControl |
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Project ID |
1751658 |
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Host Institution |
IRCCS Ospedale San Raffaele - Milan |
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Pathology of Interest |
Tumor Microenvironment |
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Research Area |
Oncology |
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Project Start Date |
1 June 2021 |
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Project End Date |
31 May 2024 |
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Funding |
€ 599.840,00 |
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Type of Project |
Individual |
PROJECT SUMMARY
Colorectal cancer (CRC) is one of the deadliest cancers. With current pharmacological therapies, only 60% of CRC patients survive more than 5 years after diagnosis. Of note, the survival rate drops to 8% in the case of liver metastasis, which is very frequent in CRC patients. In recent years, thanks to the development of new immunotherapies capable of stimulating the immune system, the survival rate of CRC patients has increased significantly, even if these therapies have proved effective in patients with a rare type of CRC liver metastases. Tumor vaccines are a form of active immunotherapy which, such as classical vaccines against pathogens, consist of administering inactivated cancer cells or tumor antigens to patients to stimulate the immune system. However, tumors have developed a variety of mechanisms to evade immune responses, and, as with other immunotherapeutic treatments, these mechanisms limit the activity of tumor vaccines. For this reason, understanding and reducing the obstacles for tumor vaccines would be useful to make them effective, thus generating a safe alternative to chemotherapy for the fight against cancer, including liver metastases. Our research group has developed lentiviral vectors (LV) that can be used to deliver therapeutic proteins to Kupffer cells (KC), a population of immune cells resident in the liver. KCs perform various functions in the liver, from the removal of toxins and cellular debris to maintaining homeostasis of the immune system.
This project aims to exploit LVs to convey tumor antigens and immune activating proteins to KCs and, thus, promote immune response to liver metastases. At the same time, KC targeting may block immunosuppressive mechanisms by which the liver suppresses the immune system, favoring the seeding of liver metastases.
Website of the principal investigator’s team: https://www.cancerbiotechnology.com/
The principal investigator of the project has published a scientific article in Cancer Cell: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00347-1#secsectitle0240