Cancer Immunology, Immunotherapy

, Volume 59, Issue 9, pp 1313–1323

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

  • Minh C. Nguyen
  • Guang Huan Tu
  • Kathryn E. Koprivnikar
  • Melissa Gonzalez-Edick
  • Karin U. Jooss
  • Thomas C. Harding
Original Article

DOI: 10.1007/s00262-010-0858-5

Cite this article as:
Nguyen, M.C., Tu, G.H., Koprivnikar, K.E. et al. Cancer Immunol Immunother (2010) 59: 1313. doi:10.1007/s00262-010-0858-5

Abstract

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.

Keywords

ImmunotherapyTumor antigenAutoantibodyProtein microarrayProstate cancerBiomarker

Supplementary material

262_2010_858_MOESM1_ESM.doc (43 kb)
Supplementary material 1 (DOC 43 kb)
262_2010_858_MOESM2_ESM.doc (30 kb)
Supplementary material 1 (DOC 29.5 kb)
262_2010_858_MOESM3_ESM.ppt (470 kb)
Supplementary material 1 (DOC 469 kb)

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Minh C. Nguyen
    • 1
  • Guang Huan Tu
    • 1
  • Kathryn E. Koprivnikar
    • 1
  • Melissa Gonzalez-Edick
    • 1
  • Karin U. Jooss
    • 1
  • Thomas C. Harding
    • 1
    • 2
  1. 1.Cell Genesys Inc.South San FranciscoUSA
  2. 2.Five Prime Therapeutics, Inc.San FranciscoUSA