Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2010-09, Vol.59 (9), p.1313-1323
• Main Authors: Nguyen, Minh C, Tu, Guang Huan, Koprivnikar, Kathryn E, Gonzalez-Edick, Melissa, Jooss, Karin U, Harding, Thomas C
• Format: Article
• Language: English
• Subjects: Antibodies - blood; Antibodies - immunology; Antineoplastic agents; Autoantibody; Biological and medical sciences; Biomarker; Biomarkers; Biomarkers, Pharmacological; Biomarkers, Tumor - immunology; Breath tests; Cancer Research; Clinical Trials as Topic; Disease Progression; Galectins - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Gynecology. Andrology. Obstetrics; High-Throughput Screening Assays; HSP90 Heat-Shock Proteins - biosynthesis; HSP90 Heat-Shock Proteins - genetics; HSP90 Heat-Shock Proteins - immunology; Humans; Immunology; Immunotherapy; Immunotherapy, Adoptive; Male; Male genital diseases; Medical sciences; Medicine; Medicine & Public Health; Neoplasm Metastasis; Nephrology. Urinary tract diseases; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; Nuclear Proteins - immunology; Oncology; Original; Original Article; Pharmacology. Drug treatments; Prognosis; Prostate cancer; prostatic neoplasms; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - immunology; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Protein Array Analysis; Protein microarray; Retrospective Studies; Survival Analysis; Treatment Outcome; Tumor antigen; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-010-0858-5

A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that may be related to immunotherapy potency. In this study, protein microarrays containing >8,000 human proteins were screened with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting whole cell immunotherapy. Thirty-three proteins were identified that displayed significantly elevated (P ≤ 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis, galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1 was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived antibody responses.