Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy.
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 <or= 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.
Nguyen
Minh C
MC
Cell Genesys Inc., South San Francisco, CA 94080, USA.
Tu
Guang Huan
GH
Koprivnikar
Kathryn E
KE
Gonzalez-Edick
Melissa
M
Jooss
Karin U
KU
Harding
Thomas C
TC
D000906:Antibodies / Q000097:blood* / Q000276:immunology; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor / Q000276:immunology; D002986:Clinical Trials as Topic; D018450:Disease Progression; D037161:Galectins / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D057166:High-Throughput Screening Assays; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D040081:Protein Array Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D000906:Antibodies; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D037161:Galectins; D018841:HSP90 Heat-Shock Proteins; C091991:LGALS8 protein, human; D009687:Nuclear Proteins; C413185:TARP; C092306:TRAP1 protein, human; D016178:Granulocyte-Macrophage Colony-Stimulating Factor