Cancer Immunology, Immunotherapy

, Volume 59, Issue 9, pp 1313–1323 | Cite as

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

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

Immunotherapy Tumor antigen Autoantibody Protein microarray Prostate cancer Biomarker 

Notes

Acknowledgments

Research support was provided by Cell Genesys, Inc., South San Francisco, CA.

Conflict of interest statement

Authors MN, GT, KK, ME, KJ and TH received financial and stock support from Cell Genesys, Inc. as their primary source of employment.

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)

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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

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