Cancer Immunotherapy Modulates Tumor Immunophenotype

Cancer immunotherapy advances have achieved clinical success by significantly increasing the survival rate of patients undergoing cancer treatment. But there is an unmet medical need due to the low response rate to checkpoint inhibitors caused by the low immune reactivity of cancer cells in “cold” tumors.

In their efforts to turn “cold” tumors into “hot” tumors, many pharmaceutical companies have been focusing on utilizing the innate immune regulatory protein known as STING to increase the immunoreactivity of tumors and the infiltration of immune cells into the tumor microenvironment (TME).

Research on STING Activators

Since clinical trials on the first STING agonist, ADU-S100, were suspended in 2020, there is an urgent need to develop new STING activators.

‘STING agonists administered by intravenous injection can be applied to combination cancer therapies and current standard treatments, like radiation therapy, chemotherapy, and monotherapy.’
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Once the STING agonist was stimulated by a compound, it induced the secretion of cytokines such as interferons (IFNs) and activated an innate immune response mediated by T cells.

The activated immune system altered the immune phenotype of the tumor, turning it from “cold” with a low reactivity to T cells to “hot” with a high reactivity, leading to the recruitment of T cells in the TME.

In this study, compound administration effectively inhibited the growth of cancer cells in mice models.In particular, 20% of the treated group was found to be tumor-free as a result of the complete elimination of their tumors.

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Scientists at the University of Michigan School of Pharmacy and the Rogel Cancer Center done research on the nutritional metal ions, which we absorb from food, and are important for immune regulation.

Also, immunological memory suppressed the growth of recurrent tumors without need for additional drug administration. Ultimately, no tumor growth was observed in the tumor-free group after the first treatment.

Most of the existing STING agonists were subjected to intratumoral administration, which limited the broad application of cancer treatment, whereas the compound in this study was able to be administered by intravenous injection.

This agent is also able to be applied to combination cancer therapies and current standard treatments, such as radiation therapy, chemotherapy, and monotherapy.

Dr. Lee stated, “Everyone dreams of vanquishing cancer; however, the development of cancer immunotherapeutic for ailments such as brain tumors is still limited.”

“We hope that this study can provide the seeds for new therapeutic strategies for cancers where immunotherapy has had limited application.”

Source-Medindia