XueXiang Du,

Ph.D., Professor, and Ph.D. Supervisor

Deputy Director of Shandong Provincial Key Laboratory of Malignant Tumor Diagnosis and Treatment, Recipient of the Shandong Overseas Outstanding Youth Fund, Taishan Scholar Young Expert, Leading Talent of Haiyou Famous Innovators Team in Jinan, First-Level Qilu Young Scholar.

Education and Professional Experience:

• 2009-2015: Pursued integrated Master's and Ph.D. studies at the Institute of Biophysics, Chinese Academy of Sciences, in the Infection and Immunity Research Center under the guidance of Professor Shengdian Wang.

• Subsequently, conducted postdoctoral research and served as a research assistant at the Children's National Medical Center and the University of Maryland School of Medicine, under the mentorship of Professors Yang Liu and Pan Zheng.

• Joined the Department of Immunology, School of Basic Medicine, Shandong University on August 27, 2021, establishing the Shandong University Tumor Immunology Team and serving as an independent PI.

Research Focus:

Dr. Du's team concentrates on enhancing the efficacy and reducing the toxicity of cancer immunotherapy. They have made significant contributions to understanding antitumor mechanisms, developing animal models for immune-related adverse events (irAEs), investigating irAEs mechanisms, and devising strategies to mitigate irAEs while enhancing antitumor immunity. As the first or corresponding author, Dr. Du has published in prestigious journals including Cell Research (three articles), Science Translational Medicine, and Journal of Hepatology. Two of his articles were recognized as top-four annual best papers by Cell Research and highly recommended by F1000 for their "New Findings/Interesting Hypotheses/Technical Advances." Additional collaborative works have appeared in eLife (2023), Cell Metabolism (2022), J Clin Invest. (2022), and STTT (2022).

Editorial and Reviewer Roles:

• Editorial Board Member of Fundamental Research (National Natural Science Foundation of China) and Cancer Advances (Chinese Anti-Cancer Association).

• Review Editor for T Cell Biology and Antigen Presenting Cell Biology at Frontiers in Immunology.

• Reviewer for the National Natural Science Foundation of China's Youth, General Program, and Regional projects, as well as multiple projects for the Provincial Department of Science and Technology.

Clinical Trials and Collaborations:

• The ADCC-enhanced, pH-sensitive CTLA-4 antibody ONC-392, developed based on novel mechanisms of anticancer activity and irAEs, is in international clinical trials (NCT04140526/NCT05446298/NCT05682443/NCT05671510/CTR20202042/CTR20223247).

• ONC-392 received Fast Track designation by the FDA on April 26, 2022, for monotherapy in metastatic NSCLC patients refractory to PD-(L)1 antibody therapy.

• On February 9, 2023, the Phase 1b clinical study of ONC-392 for liver, stomach, esophageal, and anal cancer commenced at Sun Yat-sen University Cancer Center, led by Dean Ruihua Xu.

• On September 15, 2023, the registration for a Chinese Phase III lung cancer clinical trial was completed, initiating an international multicenter trial across 91 hospitals in Europe, the United States, Canada, South Korea, and China, chaired by Professor Yilong Wu of Guangdong Provincial People's Hospital.

• On March 20, 2023, BioNTech and OncoC4 announced a strategic partnership, with BioNTech acquiring global rights to ONC-392. OncoC4 received a $200 million upfront payment and is eligible for additional milestone payments and double-digit sales royalties.

Innovative Contributions:

• The CD24Fc, for the treatment of irAEs, has entered Phase I/II clinical trials in the United States (NCT04552704).

• The CTLA-4-Ig mutant developed for the treatment and prevention of irAEs has been patented internationally (WO2018053506A1).

Future Research Directions:

1. The team will further validate and develop new cancer immunotherapy strategies based on potential targets and biomarkers identified through second-generation sequencing data from mouse tumor models and clinical samples.

2. They will explore the mechanism of a candidate gene mutation associated with CTLA-4 antibody therapy response and validate its potential as a biomarker in new clinical trials.

3. Clinical exploratory trials will continue to investigate biomarkers for effective and safe CTLA-4 antibody therapy and reasons for non-response in some patients.

4. Two pioneering irAEs animal models will be used to explore new strategies and mechanisms to reduce irAEs without compromising antitumor immunotherapy efficacy.

5. The team will investigate new mechanisms of Anti-Drug-Antibody (ADA) production to develop safer and more effective humanized antibodies.

6. They will explore the connection between CTLA-4 and 4-1bb to discover new combination strategies for improving the efficacy and safety of antibody therapy for cancer.

Join Our Team:

Our laboratory is continuously recruiting talented individuals, including postdoctoral researchers, assistant researchers, associate researchers, researchers, associate professors, and Co-PIs, to enhance the efficacy and safety of cancer immunotherapy. We also welcome outstanding students to apply for graduate studies in our group.