A Potential Drug Candidate for Tumor-targeting Immunotherapy was Constructed and Verified by IAE Researchers

Release Time:2020-06-16 Big Small

Recently years, tumor immunotherapy is becoming a hot spot and future trend in the field of cancer research. In this process, the specific targeting to tumor tissues and the effectiveness in activating the immune system in the tumor microenvironment (TME) are the KEY points to the successful cancer immunotherapy. As a promising immunopotentiator, superantigen can effectively activate the body's immune response and elicit potent cytotoxic effects to tumor cells and solid tumors even at extremely low doses. It is therefore a promising tumor immunotherapeutic agent.

The Research Group of Microbial Resources and Ecology at the Institute of Applied Ecology, Chinese Academy of Sciences, which is also based on Shenyang Key Laboratory of Superantigen Research, is committed to the study of the structure-activity relationship of superantigen biomacromolecules, structural improvement and the development of immune and antitumor drugs. The Research Group continuously undertakes National Science and Technology Major Specific Projects of China for “Significant Creation of New Drugs”, including the 11th and the 12th Five-Year Plan of the Ministry of Science and Technology, and the Strategic Priority Research Program of the Chinese Academy of Sciences Grant.

Recently, Professor Mingkai Xu and his colleagues innovatively constructed a tumor-targeting superantigen named ST-4-iRGD using genetic engineering technology. In their study, murine breast cancer cell line 4T1 and melanoma cell line B16F10 were set as the targets to systematically evaluate the profiles of tumor targeting and anti-tumor activities of ST-4-iRGD in in vitro cellular model and in vivo tumor-bearing mice model, respectively. Their results showed that ST-4-iRGD can penetrate into TME through iRGD-mediated tumor targeting, thus significantly enhance tumor suppression rate, reduce solid tumor sizes and greatly extend survival period. The study also found that the introduction of targeting molecules significantly enhanced the distribution of superantigens in TME, and effectively improved lymphocyte infiltration in solid tumor tissues, which exerted a stronger tumor immunotherapy effect. In addition, no toxic effects caused by ST-4-iRGD were found during the entire research process, suggesting excellent prospects for a new drug development.

The study entitled An iRGD peptide fused superantigen mutant induced tumor-targeting and T lymphocyte infiltrating in cancer immunotherapy” has been published in International Journal of Pharmaceutics, a Pharmaceutical Top Journal.

This study was funded by the Strategic Priority Research Program of the Chinese Academy of Sciences Grant, Liaoning Xingliao Talent Programme, and the Young and Middle-aged S&T Innovative Talent Programme of Shenyang Science and Technology Bureau.

Publication Name: XU Mingkai et al.