Health
Cancer immunotherapy that can regulate the immune phenotype of tumors
The chemical structure and mechanism of action of the STING agonist using the 4c compound developed in this study (left), and the results and schematic diagram of the anticancer effect in an animal model (right). Credit: Korea Institute of Science and Technology (KIST)
Innovations in cancer immunotherapy have been clinically successful by significantly increasing the survival rates of patients receiving cancer treatment. However, unmet medical needs still exist due to the low immunoreactivity of cancer cells in “cold” tumors and the low response rate to checkpoint inhibitors. In an effort to turn “cold” tumors into “hot” tumors, many global pharmaceutical companies utilize a natural immunomodulatory protein known as STING for tumor immunoreactivity and tumor microenvironment (TME). The focus is on increasing the infiltration of immune cells. ). However, clinical trials of the first STING agonist, ADU-S100, were discontinued in 2020, so there is an urgent need to develop new STING activators.
Under these circumstances, a research team led by Dr. Lee Sang-gi of the Institute of Brain Science, Korea Institute of Science and Technology and Dr. Kim Hae-jin of the Research Center for Infectious Diseases, Korea Institute of Chemical Technology announced the development. Development of a new small molecule STING agonist.
When the STING agonist was stimulated by the compound, it induced the secretion of cytokines such as interferon (IFN) and activated the T cell-mediated innate immune response.activation Immune system It changed the immune phenotype of the tumor from a less responsive “cold” state to a more responsive “hot” state and mobilized T cells to TME.
In this study, administration of the compound effectively suppressed the growth of cancer cells in a mouse model. In particular, 20% of the treatment groups were found to be tumor-free as a result of complete removal of the tumor. moreover, Immunological memory It suppressed the growth of recurrent tumors without the need for additional drug administration. Finally, no tumor growth was observed in the tumor-free group after the first treatment.
Most of the existing STING agonists received intratumoral administration, so Cancer treatmentOn the other hand, the compounds in this study could be administered by intravenous injection. From the perspective of further drug development, the drug can also be applied in combination with cancer treatments and current standard therapies such as radiation therapy, chemotherapy, and monotherapy.
“Everyone dreams of defeating cancer, but the development of cancer immunotherapy for diseases such as brain tumors is still limited. This study has limited use of immunotherapy for cancer,” said Dr. Lee. I hope it will be the seed of a new treatment strategy for the disease. “
The study was published in Journal of Medicinal Chemistry..
Min Jae Jeon et al, Development of potent immunomodulators targeting interferon gene receptor stimulators, Journal of Medicinal Chemistry (2022). DOI: 10.1021 / acs.jmedchem.1c01795
Provided by the National Council of Science and Technology
Quote: Cancer immunotherapy that can regulate tumor immunotherapy (May 31, 2022) is available from https: //medicalxpress.com/news/2022-05-cancer-immunotherapy-capable-modulating-tumor.html 5 of 2022. Obtained on the 31st of March.
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