title: Sustained complete response to CTLA-4 blockade in a patient with metastatic, castration-resistant prostate cancer.
abstract: We present the case of a man with metastatic, castration-resistant prostate cancer, who had a complete prostate-specific antigen (PSA) response after 2½ doses of ipilimumab. His treatment course was complicated by diarrhea and autoimmune hepatitis, both of which resolved within 4 months. Sera and biopsy specimens were accessed, and sera from pretreatment and day 113 were analyzed. Augmented antibody responses were detected against 11 potential tumor antigens, with responses ranging from 5- to 20-fold in day 113 sera compared with baseline. Genes that were targets of a strong antibody response (arbitrarily set at 10-fold or greater increase) were analyzed by real-time PCR for expression in the tumor biopsy cDNA. Of the top 5 genes, only 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) could be identified in the amplified tumor biopsy cDNA. Using an antibody to HIBCH, immunohistochemical analysis documented strong expression of the protein. Together, these data suggest that an augmented antibody response to HIBCH, an antigen that was expressed by the patient's prostate cancer, could have contributed to the clinical response. After 16 months of PSA stability, he discontinued his androgen-suppression therapy. With the return of his testosterone, his PSA increased slightly, likely originating from his intact prostate. He has been disease free for the past 6 years without any additional therapy.
authors.affiliation: Authors' Affiliations: Department of Pathology, Providence Health System, Portland, Oregon.
authors.forename: Julie N
authors.initials: JN
authors.lastname: Graff
authors.forename: Sachin
authors.initials: S
authors.lastname: Puri
authors.forename: Carlo B
authors.initials: CB
authors.lastname: Bifulco
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Fox
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D019693:Hepatitis, Autoimmune / Q000150:complications / Q000188:drug therapy; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; D000074324:Ipilimumab; D017430:Prostate-Specific Antigen