Sustained complete response to CTLA-4 blockade in a patient with metastatic, castration-resistant prostate cancer

Julie Graff, Sachin Puri, Carlo B. Bifulco, Bernard A. Fox, Tomasz (Tom) Beer

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)399-403
Number of pages5
JournalCancer immunology research
Volume2
Issue number5
DOIs
StatePublished - May 1 2014

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Castration
Prostate-Specific Antigen
Antibody Formation
Prostatic Neoplasms
3-hydroxyisobutyryl-CoA hydrolase
Hydrolases
Coenzyme A
Biopsy
Complementary DNA
Serum
Autoimmune Hepatitis
Neoplasm Antigens
Androgens
Genes
Testosterone
Real-Time Polymerase Chain Reaction
Prostate
Diarrhea
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sustained complete response to CTLA-4 blockade in a patient with metastatic, castration-resistant prostate cancer. / Graff, Julie; Puri, Sachin; Bifulco, Carlo B.; Fox, Bernard A.; Beer, Tomasz (Tom).

In: Cancer immunology research, Vol. 2, No. 5, 01.05.2014, p. 399-403.

Research output: Contribution to journalArticle

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