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01.02.2012 | Original article

Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients

verfasst von: Ray Wilkinson, Katherine Woods, Rachael D’Rozario, Rebecca Prue, Frank Vari, Melinda Y. Hardy, Ying Dong, Judith A. Clements, Derek N. J. Hart, Kristen J. Radford

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 2/2012

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Abstract

Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the lack of suitable target antigens that are recognized by CD8⁺ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested. These CTL lysed HLA-A*0201⁺ KLK4 ⁺ cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes from prostate cancer antigens; prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP). These data demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL responses and identify it as an attractive target for prostate and ovarian cancer immunotherapy.

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Vulink A, Radford KJ, Melief C, Hart DN (2008) Dendritic cells in cancer immunotherapy. Adv Cancer Res 99:363–407PubMedCrossRef

Drake CG (2010) Prostate cancer as a model for tumour immunotherapy. Nat Rev Immunol 10(8):580–593PubMedCrossRef

Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM (2006) Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 24(19):3089–3094PubMedCrossRef

Correale P, Walmsley K, Nieroda C, Zaremba S, Zhu M, Schlom J, Tsang KY (1997) In vitro generation of human cytotoxic T lymphocytes specific for peptides derived from prostate-specific antigen. J Natl Cancer Inst 89(4):293–300PubMedCrossRef

Murphy GP, Tjoa BA, Simmons SJ, Ragde H, Rogers M, Elgamal A, Kenny GM, Troychak MJ, Salgaller ML, Boynton AL (1999) Phase II prostate cancer vaccine trial: report of a study involving 37 patients with disease recurrence following primary treatment. Prostate 39(1):54–59PubMedCrossRef

Lodge PA, Jones LA, Bader RA, Murphy GP, Salgaller ML (2000) Dendritic cell-based immunotherapy of prostate cancer: immune monitoring of a phase II clinical trial. Cancer Res 60(4):829–833PubMed

Lu J, Celis E (2002) Recognition of prostate tumor cells by cytotoxic T lymphocytes specific for prostate-specific membrane antigen. Cancer Res 62(20):5807–5812PubMed

Peshwa MV, Shi JD, Ruegg C, Laus R, van Schooten WC (1998) Induction of prostate tumor-specific CD8+ cytotoxic T-lymphocytes in vitro using antigen-presenting cells pulsed with prostatic acid phosphatase peptide. Prostate 36(2):129–138PubMedCrossRef

Olson BM, Frye TP, Johnson LE, Fong L, Knutson KL, Disis ML, McNeel DG (2010) HLA-A2-restricted T-cell epitopes specific for prostatic acid phosphatase. Cancer Immunol Immunother 59(6):943–953PubMedCrossRef

10.

Khazaie K, Bonertz A, Beckhove P (2009) Current developments with peptide-based human tumor vaccines. Curr Opin Oncol 21(6):524–530PubMedCrossRef

11.

Clements JA, Willemsen NM, Myers SA, Dong Y (2004) The tissue kallikrein family of serine proteases: functional roles in human disease and potential as clinical biomarkers. Crit Rev Clin Lab Sci 41(3):265–312PubMedCrossRef

12.

Nelson PS, Gan L, Ferguson C, Moss P, Gelinas R, Hood L, Wang K (1999) Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression. Proc Natl Acad Sci USA 96(6):3114–3119PubMedCrossRef

13.

Yousef GM, Obiezu CV, Luo LY, Black MH, Diamandis EP (1999) Prostase/KLK-L1 is a new member of the human kallikrein gene family, is expressed in prostate and breast tissues, and is hormonally regulated. Cancer Res 59(17):4252–4256PubMed

14.

Stephenson SA, Verity K, Ashworth LK, Clements JA (1999) Localization of a new prostate-specific antigen-related serine protease gene, KLK4, is evidence for an expanded human kallikrein gene family cluster on chromosome 19q13.3-13.4. J Biol Chem 274 (33):23210–23214

15.

Shaw JL, Diamandis EP (2007) Distribution of 15 human kallikreins in tissues and biological fluids. Clin Chem 53(8):1423–1432PubMedCrossRef

16.

Xi Z, Klokk TI, Korkmaz K, Kurys P, Elbi C, Risberg B, Danielsen H, Loda M, Saatcioglu F (2004) Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer. Cancer Res 64(7):2365–2370PubMedCrossRef

17.

Dong Y, Bui LT, Odorico DM, Tan OL, Myers SA, Samaratunga H, Gardiner RA, Clements JA (2005) Compartmentalized expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms. Endocr Relat Cancer 12(4):875–889PubMedCrossRef

18.

Veveris-Lowe TL, Lawrence MG, Collard RL, Bui L, Herington AC, Nicol DL, Clements JA (2005) Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells. Endocr Relat Cancer 12(3):631–643PubMedCrossRef

19.

Klokk TI, Kilander A, Xi Z, Waehre H, Risberg B, Danielsen HE, Saatcioglu F (2007) Kallikrein 4 is a proliferative factor that is overexpressed in prostate cancer. Cancer Res 67(11):5221–5230PubMedCrossRef

20.

Day CH, Fanger GR, Retter MW, Hylander BL, Penetrante RB, Houghton RL, Zhang X, McNeill PD, Filho AM, Nolasco M, Badaro R, Cheever MA, Reed SG, Dillon DC, Watanabe Y (2002) Characterization of KLK4 expression and detection of KLK4-specific antibody in prostate cancer patient sera. Oncogene 21(46):7114–7120PubMedCrossRef

21.

Hural JA, Friedman RS, McNabb A, Steen SS, Henderson RA, Kalos M (2002) Identification of naturally processed CD4 T cell epitopes from the prostate-specific antigen kallikrein 4 using peptide-based in vitro stimulation. J Immunol 169(1):557–565PubMed

22.

Parker KC, Bednarek MA, Coligan JE (1994) Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol 152(1):163–175PubMed

23.

Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S (1999) SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50(3–4):213–219PubMedCrossRef

24.

Radford KJ, Turtle CJ, Kassianos AJ, Vuckovic S, Gardiner D, Khalil D, Taylor K, Wright S, Gill D, Hart DN (2005) Immunoselection of functional CMRF-56 + blood dendritic cells from multiple myeloma patients for immunotherapy. J Immunother 28(4):322–331PubMedCrossRef

25.

Rabinovich GA, Gabrilovich D, Sotomayor EM (2007) Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol 25:267–296PubMedCrossRef

26.

Bondurant KL, Crew MD, Santin AD, O’Brien TJ, Cannon MJ (2005) Definition of an immunogenic region within the ovarian tumor antigen stratum corneum chymotryptic enzyme. Clin Cancer Res 11(9):3446–3454PubMedCrossRef

27.

Wei ML, Cresswell P (1992) HLA-A2 molecules in an antigen-processing mutant cell contain signal sequence-derived peptides. Nature 356(6368):443–446PubMedCrossRef

28.

Henderson RA, Michel H, Sakaguchi K, Shabanowitz J, Appella E, Hunt DF, Engelhard VH (1992) HLA-A2.1-associated peptides from a mutant cell line: a second pathway of antigen presentation. Science 255(5049):1264–1266

29.

El Hage F, Stroobant V, Vergnon I, Baurain JF, Echchakir H, Lazar V, Chouaib S, Coulie PG, Mami-Chouaib F (2008) Preprocalcitonin signal peptide generates a cytotoxic T lymphocyte-defined tumor epitope processed by a proteasome-independent pathway. Proc Natl Acad Sci USA 105(29):10119–10124PubMedCrossRef

30.

Wolfel T, Van Pel A, Brichard V, Schneider J, Seliger B, Meyer zum Buschenfelde KH, Boon T (1994) Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes. Eur J Immunol 24(3):759–764PubMedCrossRef

31.

Wolfel C, Drexler I, Van Pel A, Thres T, Leister N, Herr W, Sutter G, Huber C, Wolfel T (2000) Transporter (TAP)- and proteasome-independent presentation of a melanoma-associated tyrosinase epitope. Int J Cancer 88(3):432–438PubMedCrossRef

32.

Correa I, Plunkett T, Coleman J, Galani E, Windmill E, Burchell JM, Taylor-Papdimitriou J (2005) Responses of human T cells to peptides flanking the tandem repeat and overlapping the signal sequence of MUC1. Int J Cancer 115(5):760–768PubMedCrossRef

33.

Oh S, Terabe M, Pendleton CD, Bhattacharyya A, Bera TK, Epel M, Reiter Y, Phillips J, Linehan WM, Kasten-Sportes C, Pastan I, Berzofsky JA (2004) Human CTLs to wild-type and enhanced epitopes of a novel prostate and breast tumor-associated protein, TARP, lyse human breast cancer cells. Cancer Res 64(7):2610–2618PubMedCrossRef

34.

Dannull J, Diener PA, Prikler L, Furstenberger G, Cerny T, Schmid U, Ackermann DK, Groettrup M (2000) Prostate stem cell antigen is a promising candidate for immunotherapy of advanced prostate cancer. Cancer Res 60(19):5522–5528PubMed

35.

Thomas S, Stauss HJ, Morris EC (2010) Molecular immunology lessons from therapeutic T-cell receptor gene transfer. Immunology 129(2):170–177PubMedCrossRef

36.

Appay V, Douek DC, Price DA (2008) CD8 + T cell efficacy in vaccination and disease. Nat Med 14(6):623–628PubMedCrossRef

37.

Dong Y, Kaushal A, Bui L, Chu S, Fuller PJ, Nicklin J, Samaratunga H, Clements JA (2001) Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas. Clin Cancer Res 7(8):2363–2371PubMed

38.

Davidson B, Xi Z, Klokk TI, Trope CG, Dorum A, Scheistroen M, Saatcioglu F (2005) Kallikrein 4 expression is up-regulated in epithelial ovarian carcinoma cells in effusions. Am J Clin Pathol 123(3):360–368PubMedCrossRef

39.

Mange A, Desmetz C, Berthes ML, Maudelonde T, Solassol J (2008) Specific increase of human kallikrein 4 mRNA and protein levels in breast cancer stromal cells. Biochem Biophys Res Commun 375(1):107–112PubMedCrossRef

40.

Zhang B (2008) Targeting the stroma by T cells to limit tumor growth. Cancer Res 68(23):9570–9573PubMedCrossRef

41.

Hombach J, Pircher H, Tonegawa S, Zinkernagel RM (1995) Strictly transporter of antigen presentation (TAP)-dependent presentation of an immunodominant cytotoxic T lymphocyte epitope in the signal sequence of a virus protein. J Exp Med 182(5):1615–1619PubMedCrossRef

42.

Wolkers MC, Brouwenstijn N, Bakker AH, Toebes M, Schumacher TN (2004) Antigen bias in T cell cross-priming. Science 304(5675):1314–1317PubMedCrossRef

43.

Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W (2000) Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood 96(9):3102–3108PubMed

44.

Avgeris M, Mavridis K, Scorilas A (2010) Kallikrein-related peptidase genes as promising biomarkers for prognosis and monitoring of human malignancies. Biol Chem 391(5):505–511PubMedCrossRef

Titel: Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients
verfasst von: Ray Wilkinson
Katherine Woods
Rachael D’Rozario
Rebecca Prue
Frank Vari
Melinda Y. Hardy
Ying Dong
Judith A. Clements
Derek N. J. Hart
Kristen J. Radford
Publikationsdatum: 01.02.2012
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 2/2012
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1095-2

Springer Medizin

Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients

Abstract

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Springer Medizin

Abstract

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