New immunotherapy method turns active particularly in tumor

A chemical method for targeting the effects of cancer-fighting immunotherapy drugs.

Immunotherapy is a promising approach against cancer. However, immunotherapy drugs are so potent that they cause harm to non-cancerous cells and the rest of the human body.

Immunotherapy drugs activate the patient’s immune cells –T-cells, NK cells. The drugs then help these cells fight against cancer

Once injected, the drugs spread all over – not just where the tumor or any metastases are located. The problem is that the proteins in the drugs are so vital that they damage healthy tissue.

EPFL scientists have developed a chemical method that targets the effects of cancer-fighting immunotherapy drugs only to the tumor tissue. In this method, the immunotherapy proteins become active when they come into the tumor tissues.

Scientists were able to develop this kind of technology thanks to a cross-disciplinary approach.

Li Tang, head of the Laboratory of Biomaterials for Immunoengineering at EPFL’s School of Engineering, said, “Our method draws on techniques from both chemistry and immune engineering.”

Yu Zhao, a postdoc at Tang’s lab, said, “The development began by utilizing the chemical properties around tumors. The tumor microenvironment is different from the rest of the body. The pH is lower, meaning it’s more acidic, and it has a high reducing potential.”

Using these facts, scientists created a kind of polymer shield for the protein drugs that would let them travel harmlessly through the body until they reach the tumor.

Zhao said, “To create the shield, I first developed stimuli-responsive chemical bonds that attach to the surface of the protein molecules, like little hooks. Then I took polymers – which are long chains of molecules – and ‘hooked’ them to the bonds on of the protein molecules. Once attached to the protein surface, the polymers wrap around them, like a protective shield.”

Tang said, “Chemical reactions in the tumor microenvironment break the bonds at the protein surface, thereby removing the polymer shield. The protein drugs are then free to activate the patient’s cancer-fighting lymphocytes selectively in the tumor tissue.”

However, the method will take several years to become clinically available to treat cancer.

Journal Reference:
  1. Yu Zhao, Yu-Qing Xie et al. Switchable immune modulator for tumor-specific activation of anticancer immunity. DOI: 10.1126/sciadv.abg7291

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