By combining a checkpoint inhibitor with a new immunocytokine, scientists at EPFL, Ludwig Institute for Cancer Research, CHUV and Roche have made a breakthrough in fighting against immunotherapy-resistant cancers.

Immunotherapy is a way of treating cancer by reprogramming the patient's immune system to attack their tumor. This cutting-edge approach has significantly impacted the treatment of cancer patients, and already boasts cases of long-term remission.

Nonetheless, many patients still either don't respond to immunotherapy, or if they do, the effects are temporary, which highlights how crucial it is that we better understand the mechanisms leading to cancers resisting this kind of treatment.

In a new study, scientists have found a way to break down the resistance of mice with neuroendocrine pancreatic cancer. This cancer is very resistant to a type of immunotherapy called checkpoint blockade, where the patient receives a drug (a checkpoint inhibitor) that blocks proteins that normally keep immune responses from being too strong, but can also prevent immune cells (T cells) from killing cancer cells.

The study was led by the group of Douglas Hanahan at EPFL's Swiss Institute for Experimental Cancer Research, with the Ludwig Institute for Cancer Research, the Lausanne University Hospital (CHUV), the Swiss Institute for Bioinformatics, and Roche.

The scientists evaluated a type of engineered protein-antibody fusion called an immunocytokine, which is increasingly used in immunotherapy. They focused on the bispecific immunocytokine PD1-IL2v, which is newly developed by Roche and can home into tumors, wherein it activates killer T cells to attack the cancer cells driving tumor growth.

The researchers combined the immunocytokine PD1-IL2v with the immune checkpoint inhibitor anti-PD-L1, thereby enhancing anti-tumor immunity against immunotherapy-resistant tumors. '[PD1-IL2v] is even more effective when combined with an immune checkpoint inhibitor, anti-PD-L1,' write the authors.

Read more at:

https://actu.epfl.ch/news/drug-combo-breaks-down-cancer-resistance-to-immuno/

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