Collecting duct carcinoma (CDC) of the kidney is a rare and highly aggressive malignant tumor with the worst prognosis among all renal cancers. Nevertheless, the first-line treatments, including chemotherapy and target therapy, usually show poor response to CDC. Recent studies have suggested that immunotherapy targeting personal tumor-specific neoantigens could be a promising strategy for several solid cancers. However, whether it has therapeutic potential in CDC remains unclear.
Here, we report a case of an Asian patient who underwent personalized neoantigen-based immunotherapy. The patient was diagnosed with metastatic CDC and suffered extensive tumor progression following sorafenib treatment. Based on the patient's own somatic mutational profile, a total of 13 neoantigens were identified and corresponding long-peptide vaccine and neoantigen-reactive T cells (NRTs) were prepared. After six cycles of neoantigen-based vaccination and T-cell immunotherapy, the patient was reported with stable disease status in tumor burden and significant alleviation of bone pain. Ex vivo interferon-γ enzyme-linked immunospot assay proved the reactivity to 12 of 13 neoantigens in peripheral blood mononuclear cells collected after immunotherapy, and the preferential reactivity to mutant peptides compared with corresponding wild-type peptides was also observed for 3 of the neoantigens. Surprisingly, biopsy sample collected from CDC sites after 3 months of immunotherapy showed decreased mutant allele frequency corresponding to 92% (12/13) of the neoantigens, indicating the elimination of tumor cells carrying these neoantigens.
Our case report demonstrated that the combined therapy of neoantigen peptide vaccination and NRT cell infusion showed certain efficacy in this CDC case, even when the patient carried only a relatively low tumor mutation burden. These results indicated that the personalized neoantigen-based immunotherapy was a promising new strategy for advanced CDC.
ChiCTR1800017836.
Journal for immunotherapy of cancer. 2020 May [Epub]
Yongyi Zeng, Wei Zhang, Zhenli Li, Youshi Zheng, Yingchao Wang, Geng Chen, Liman Qiu, Kun Ke, Xiaoping Su, Zhixiong Cai, Jingfeng Liu, Xiaolong Liu
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China., Department of Respiratory and Critical Care Medicine, Changhai Hospital of The Second Military Medical University, Shanghai 200433, China., Institute of Cardiovascular Development and Translational Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China., The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China .