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-gamma　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.