Personalized neoantigen-based immunotherapy for advanced collecting duct carcinoma: case report

BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSIONS: 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. TRIAL REGISTRATION NUMBER: ChiCTR1800017836.