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Cocktail Treatment for Promoting Cancer-Immunity Cycle
Research team from the Changchun Institute of Applied Chemistry of the Chinese Academy of Sciences develop an innovative combination of treatments to enhance cancer-immunity cycle.

The cancer-immunity cycle is an immune system response triggered by the release of cancer cell antigens. This process generates T cells responses to identify and eliminate cancer cells. Immune checkpoint blockade therapy (ICT) has seen some promise in treating multiple tumours, however clinical application has been disrupted by poor response rates.

Combination treatments in an effort to enhance the efficacy of ICT have been developed, but has shown limited tumour inhibition after testing on a number of tumour models.

In a recent study published in Science Advances by a research team led by Professor Tian Huayu from the Changchun Institute of Applied Chemistry (CIAC) of the Chinese Academy of Science formulated an original idea that combines ICT together with other therapeutic approaches. This new cocktail therapy is said to achieve enhancement of the cancer-immunity cycle through a nano-delivery system.

The team proposed that the anti-tumour treatment use a concoction of immunogenic chemotherapy, immune checkpoint blockade, and extracellular matrix elimination. This cocktail therapy will comprise of two types of tumour microenvironment responsive drugs and gene delivery nano-particles. Targeted delivery of doxorubicin and co-delivery of plasmids expressing small RNA of PD-L1 and hyaluronidase to the tumour region could be achieved with the nano-delivery system – leading to improved therapeutic effects.

This proposed cocktail therapy could also facilitate T cell priming by inducing tumour immunogenic cell death and directing an immunosuppressive tumour microenvironment to an immuno-active phenotype.

Multiple tumour types demonstrated to have outstanding immunotherapeutic effects. Using the cocktail therapy on B16F10, CT26 and 4T1 tumour models, drastic shrinkage of the tumour was achieved, showing more efficient therapeutic effect as compared to traditional combination of chemotherapy and ICT.

"These excellent outcomes are mainly attributed to the increasing amount of peripheral CD8+ T cell infiltration in tumours, which can also induce strong immune memory effects and effectively prevent tumour metastasis," said Professor Tian.

The study shows potential of a more comprehensive immunotherapy strategy that integrates multiple aspects of the cancer-immunity cycle, such as tumour antigen release, T cell trafficking from the periphery to the tumour, effective killing of tumour cells, and the generation of immune memory T cells.

This study provides a new method of combining different cancer treatment options with ICT as a way to formulate more efficient anti-tumour immunotherapies for multiple types of tumours.


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