Cause of blocking immune anticancer discovered... New treatment path for lung cancer discovered

A new treatment for lung cancer has opened. It is expected to enter clinical trials in 2028.



The development of immune checkpoint inhibitors (immunotherapy) that help our body's immune cells better attack cancer cells has brought about a groundbreaking leap forward in cancer treatment. In reality, less than 20% of all patients respond.



There is an urgent need for new treatment strategies for patients who respond or do not respond to immunotherapy.



A KAIST research team discovered DDX54, a key factor that induces resistance to immunotherapy by suppressing the infiltration of immune cells into cancer tissue when lung cancer cells acquire the ability to evade immunity. [Photo = KAIST]



A research team at the Korea Advanced Institute of Science and Technology (KAIST) has discovered a key factor (DDX54) that interferes with immunotherapy for the first time, opening a new path for lung cancer treatment. This technology has been transferred to the faculty startup Biolivert and is being developed as an actual companion treatment for immunotherapy, and clinical trials are scheduled for 2028.



KAIST (President Lee Kwang-hyung) announced on the 8th that Professor Cho Kwang-hyun's research team in the Department of Bio and Brain Engineering succeeded in discovering a key factor (DDX54) that determines the immune evasion ability of



lung cancer cells. It also announced on the 8th that it has proven that suppressing a key factor with immune evasion ability significantly improves the effectiveness of immunotherapy by



increasing the infiltration of immune cells into cancer tissue. Immunotherapy is an excellent treatment method that uses anti-PD-1 or anti-PD-L1 antibodies that help attack immune cells. Since the response rate of immunotherapy is low, the number of patients who actually benefit from the treatment has been extremely limited.



Recently, the Tumor Mutational Burden (TMB) was approved by the FDA as a major biomarker for immunotherapy as a biomarker study to select patients with a high probability of responding. This means that cancers with many genetic mutations are more likely to respond to immunotherapy.



Even if TMB is high, there are still many cancers in the form of so-called 'immune desert' where immune cell infiltration is extremely limited. In this case, the response to immunotherapy is also reported to be very low.



The results of this study are that it is possible to overcome the resistance to immunotherapy using immune checkpoint inhibitors by suppressing the key factor discovered in lung cancer tissues with very low immune cell infiltration.



Professor Cho Kwang-hyun's research team inferred the gene regulatory network through systems biology research from transcriptome and genome data derived from lung cancer patients with immune evasion, and analyzed it to find the key regulatory factor that allows lung cancer cells to acquire immune evasion.



When the key factor was suppressed in a syngeneic lung cancer mouse model and the response to immunotherapy was investigated, the infiltration of anticancer immune cells such as T cells and NK cells into the tissue significantly increased, and the response to immunotherapy was also noticeably increased.



Professor Cho Kwang-hyun said, "The major achievement is that we have discovered for the first time the key regulatory factor that enables lung cancer cells to acquire immune evasion capabilities and developed a new treatment strategy that can induce a response in cancer that did not respond to immunotherapy by reversing the immune evasion capabilities by controlling it."



This research was participated by Dr. Gong Jeong-ryeol (first author), researcher Lee Jeong-eun (joint first author), and Dr. Han Yeong-hyeon from KAIST. The research results ((Paper title: DDX54 downregulation enhances anti-PD1 therapy in immune-desert lung tumors with high tumor mutational burden) were published on April 2 in the international journal 'Proceedings of the National Academy of Sciences (PNAS)' published by the National Academy of Sciences (NAS) of the United States of America.





https://www.inews24.com/view/blogger/1831945

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