nach oben

Cancer Immunology, Immunotherapy

Erschienen in:

01.03.2006 | Symposium in Writing

Chaperone-rich cell lysates, immune activation and tumor vaccination

verfasst von: Yi Zeng, Michael W. Graner, Emmanuel Katsanis

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 3/2006

Einloggen, um Zugang zu erhalten

Abstract

We have utilized a free-solution-isoelectric focusing technique (FS-IEF) to obtain chaperone-rich cell lysates (CRCL) fractions from clarified tumor homogenates. The FS-IEF technique for enriching multiple chaperones from tumor lysate is relatively easy and rapid, yielding sufficient immunogenic material for clinical use. We have shown that tumor-derived CRCL carry antigenic peptides. Dendritic cells (DCs) uptake CRCL and cross-present the chaperoned peptides to T cells. Tumor-derived CRCL induce protective immune responses against a diverse range of murine tumor types in different genetic backgrounds. When compared to purified heat shock protein 70 (HSP70), single antigenic peptide or unfractionated lysate, CRCL have superior ability to activate/mature DCs and are able to induce potent, long lasting and tumor specific T-cell-mediated immunity. While CRCL vaccines were effective as stand-alone therapies, the enhanced immunogenicity arising from CRCL-pulsed DC as a vaccine indicates that CRCL could be the antigen source of choice for DC-based anti-cancer immunotherapies. The nature of CRCL’s enhanced immunogenicity may lie in the broader antigenic peptide repertoire as well as the superior immune activation capacity of CRCL. Exongenous CRCL also supply danger signals in the context of apoptotic tumor cells and enhance the immunogenicity of apoptotic tumor cells, leading to tumor-specific T cell dependent long-term immunity. Moreover, CRCL based vaccines can be effectively combined with chemotherapy to treat cancer. Our findings indicate that CRCL have prominent adjuvant effects and are effective sources of tumor antigens for pulsing DCs. Tumor-derived CRCL are promising anti-cancer vaccines that warrant clinical research and development.

Albert ML, Sauter B, Bhardwaj N (1998) Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392:86–89PubMedCrossRef

Asea A, Kabingu E, Stevenson MA, Calderwood SK (2000) HSP70 peptidembearing and peptide-negative preparations act as chaperokines. Cell Stress Chaperones 5:425–431PubMedCrossRef

Baker-LePain JC, Sarzotti M, Fields TA, Li CY, Nicchitta CV (2002) GRP94 (gp96) and GRP94 N-terminal geldanamycin binding domain elicit tissue nonrestricted tumor suppression. J Exp Med 196:1447–1459PubMedCrossRef

Baker-LePain JC, Sarzotti M, Nicchitta CV (2004) Glucose-Regulated Protein 94/Glycoprotein 96 Elicits Bystander Activation of CD4+ T Cell Th1 Cytokine Production In Vivo. J Immunol 172:4195–4203PubMed

Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 1:767–811CrossRef

Basu S, Binder RJ, Ramalingam T, Srivastava PK (2001) CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14:303–313PubMedCrossRef

Basu S, Srivastava PK (1999) Calreticulin, a peptide-binding chaperone of the endoplasmic reticulum, elicits tumor- and peptide-specific immunity. J Exp Med 189:797–802PubMedCrossRef

Becker T, Hartl FU, Wieland F (2002) CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. J Cell Biol 158:1277-1285PubMedCrossRef

Bellone M, Iezzi G, Rovere P, Galati G, Ronchetti A, Protti MP, Davoust J, Rugarli C, Manfredi AA (1997) Processing of engulfed apoptotic bodies yields T cell epitopes. J Immunol 159:5391–5399PubMed

10.

Berwin B, Hart JP, Pizzo SV, Nicchitta CV (2002) Cutting edge: CD91-independent cross-presentation of GRP94(gp96)-associated peptides. J Immunol 168:4282–4286PubMed

11.

Berwin B, Hart JP, Rice S, Gass C, Pizzo SV, Post SR, Nicchitta CV (2003) Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells. Embo J 22:6127–6136PubMedCrossRef

12.

Binder RJ, Blachere NE, Srivastava PK (2001) Heat shock protein-chaperoned peptides but not free peptides introduced into the cytosol are presented efficiently by major histocompatibility complex I molecules. J Biol Chem 276:17163–17171PubMedCrossRef

13.

Binder RJ, Han DK, Srivastava PK (2000) CD91: a receptor for heat shock protein gp96. Nat Immunol 1:151–155PubMedCrossRef

14.

Blachere NE, Srivastava PK (1995) Heat shock protein-based cancer vaccines and related thoughts on immunogenicity of human tumors. Semin Cancer Biol 6:349–355PubMedCrossRef

15.

Boon T, Cerottini JC, Van den Eynde B, van der Bruggen P, Van Pel A (1994) Tumor antigens recognized by T lymphocytes. Annu Rev Immunol 12:337–365PubMedCrossRef

16.

Bosch GJ, Joosten AM, Kessler JH, Melief C.J, Leeksma OC. (1996) Recognition of BCR-ABL positive leukemic blasts by human CD4+ T cells elicited by primary in vitro immunization with a BCR-ABL breakpoint peptide. Blood 88:3522–3527PubMed

17.

Buteau C, Markovic SN, Celis E (2002) Challenges in the development of effective peptide vaccines for cancer. Mayo Clinic Proceed 77:339–349CrossRef

18.

Clark RE (2001) Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein. Blood 98:2887–2893PubMedCrossRef

19.

Corbin AS, Rosee PL, Stoffregen EP, Druker BJ, Deininger MW (2003) Several Bcr–Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib. Blood 101:4611–4614PubMedCrossRef

20.

Delneste Y, Magistrelli G, Gauchat J, Haeuw J, Aubry J, Nakamura K, Kawakami-Honda N, Goetsch L, Sawamura T, Bonnefoy J, Jeannin P (2002) Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity 17:353–362PubMedCrossRef

21.

Feng H, Zeng Y, Graner MW, Katsanis E (2002) Stressed apoptotic tumor cells stimulate dendritic cells and induce specific cytotoxic T cells. Blood 100:4108–4115PubMedCrossRef

22.

Feng H, Zeng Y, Graner MW, Likhacheva A, Katsanis E (2003) Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimulate antitumor immunity. Blood 101:245–252PubMedCrossRef

23.

Feng H, Zeng Y, Whitesell L, Katsanis E (2001) Stressed apoptotic tumor cells express heat shock proteins and elicit tumor-specific immunity. Blood 97:3505–3512PubMedCrossRef

24.

Fernandez NC, Lozier A, Flament C, Ricciardi-Castagnoli P, Bellet D, Suter M, Perricaudet M, Tursz T, Maraskovsky E, Zitvogel L (1999) Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med 5:405–411PubMedCrossRef

25.

Flynn GC, Pohl J, Flocco MT, Rothman JE (1991) Peptide-binding specificity of the molecular chaperone BiP. Nature 353:726–730PubMedCrossRef

26.

Ghiringhelli F, Larmonier N, Schmitt E, Parcellier A, Cathelin D, Garrido C, Chauffert B, Solary E, Bonnotte B, Martin F (2004) CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol 34:336–344PubMedCrossRef

27.

Godshall CJ, Scott MJ, Burch PT, Peyton JC, Cheadle WG (2003) Natural killer cells participate in bacterial clearance during septic peritonitis through interactions with macrophages. Shock 19:144–149PubMedCrossRef

28.

Gorre ME, Sawyers CL (2002) Molecular mechanisms of resistance to STI571 in chronic myeloid leukemia. Curr Opin Hematol 9:303–307PubMedCrossRef

29.

Gough MJ, Melcher AA, Ahmed A, Crittenden MR, Riddle DS, Linardakis E, Ruchatz AN, Emiliusen LM, Vile RG (2001) Macrophages orchestrate the immune response to tumor cell death. Cancer Res 61:7240–7247PubMed

30.

Graner M, Raymond A, Akporiaye E, Katsanis E (2000) Tumor-derived multiple chaperone enrichment by free-solution isoelectric focusing yields potent antitumor vaccines. Cancer Immunology, Immunotherapy 49:476–484PubMedCrossRef

31.

Graner M, Raymond A, Romney D, He L, Whitesell L, Katsanis E (2000) Immunoprotective activities of multiple chaperone proteins isolated from murine B-cell leukemia/lymphoma. Clin Cancer Res 6:909–915PubMed

32.

Graner M, Zeng Y, Feng H, Katsanis E (2003) Tumor-derived chaperone-rich cell lysates are effective therapeutic vaccines against a variety of cancers. Cancer Immunol Immunother 52:226–234PubMed

33.

Graner MW, Likhacheva A, Davis J, Raymond A, Brandenberger J, Romanoski A, Thompson S, Akporiaye E, Katsanis E (2004) Cargo from tumor-expressed albumin inhibits T-cell activation and response. Cancer Res 64:8085–8092PubMedCrossRef

34.

He L, Feng H, Raymond A, Kreeger M, Zeng Y, Graner M, Whitesell L, Katsanis E (2001) Dendritic-cell-peptide immunization provides immunoprotection against bcr-abl-positive leukemia in mice. Cancer Immunol Immunother 50:31–40PubMedCrossRef

35.

Horita M, Andreu E J, Benito A, Arbona C, Sanz C, Benet I, Prosper F, Fernandez-Luna JL (2000) Blockade of the Bcr-Abl kinase activity induces apoptosis of chronic myelogenous leukemia cells by suppressing signal transducer and activator of transcription 5-dependent expression of Bcl-xL. J Exp Med 191:977–984PubMedCrossRef

36.

Inoue K, Sugiyama H (1995) [WT 1 and leukemia]. Rinsho Ketsueki 36:552–558PubMed

37.

Janetzki S, Blachere NE, Srivastava PK (1998) Generation of tumor-specific cytotoxic T lymphocytes and memory T cells by immunization with tumor-derived heat shock protein gp96. J Immunother 21:269–276PubMedCrossRef

38.

Johansson B, Fioretos T, Mitelman F (2002) Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol 107:76–94PubMedCrossRef

39.

Johnstone RW, Ruefli AA, Lowe SW (2002) Apoptosis: a link between cancer genetics and chemotherapy. Cell 108:153–164PubMedCrossRef

40.

Kalos M (2003) Tumor antigen-specific T cells and cancer immunotherapy: current issues and future prospects. Vaccine 21:781–786PubMedCrossRef

41.

Koh LP, Hwang WY, Chuah CT, Linn YC, Goh YT, Tan CH, Ng HJ, Tan PH. (2003). Imatinib mesylate (STI-571) given concurrently with nonmyeloablative stem cell transplantation did not compromise engraftment and resulted in cytogenetic remission in a patient with chronic myeloid leukemia in blast crisis. Bone Marrow Transplant 31:305–308PubMedCrossRef

42.

Kol A, Lichtman A, Finberg RW, Libby P, Kurt-Jones EA (2000) Cutting edge: heat shock protein (HSP) 60 activates the innate immune response: CD14 is an essential receptor for HSP60 activation of mononuclear cells. J Immunol 164:13–17PubMed

43.

Kotera Y, Shimizu K, Mule JJ (2001) Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization. Cancer Res 61:8105–8109PubMed

44.

La Rosee P, O’Dwyer ME, Druker BJ (2002) Insights from pre-clinical studies for new combination treatment regimens with the Bcr-Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec) in chronic myelogenous leukemia: a translational perspective. Leukemia 16:1213–1219PubMedCrossRef

45.

Lieberman LA, Hunter CA (2002) Regulatory pathways involved in the infection-induced production of IFN-gamma by NK cells. Microbes Infect 4:1531–1538PubMedCrossRef

46.

Lim SH, Coleman S (1997) Chronic myeloid leukemia as an immunological target. Am J Hematol 54:61–67PubMedCrossRef

47.

Lindquist S (1986) The heat-shock response. Annu Rev Biochem 55:1151–1191PubMedCrossRef

48.

Mazzaferro V, Coppa J, Carrabba MG, Rivoltini L, Schiavo M, Regalia E, Mariani L, Camerini T, Marchiano A, Andreola S, Carmerini R, Corsi M, Lewis JJ, Srivastava PK, Parmiani G (2003) Vaccination with autologous tumor-derived heat-shock protein gp96 after liver resection for metastatic colorectal cancer. Clin Cancer Res 9:3235–3245PubMed

49.

Melcher A, Todryk S, Hardwick N, Ford M, Jacobson M, Vile RG (1998) Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat Med 4:581–587PubMedCrossRef

50.

Menoret A, Peng P, Srivastava PK (1999) Association of peptides with heat shock protein gp96 occurs in vivo and not after cell lysis. Biochem Biophys Res Commun 262:813–818PubMedCrossRef

51.

Molldrem JJ, Clave E, Jiang YZ, Mavroudis D, Raptis A, Hensel N, Agarwala V, Barrett AJ (1997) Cytotoxic T lymphocytes specific for a nonpolymorphic proteinase 3 peptide preferentially inhibit chronic myeloid leukemia colony-forming units. Blood 90:2529–2534PubMed

52.

Nakao S (2002) Identification of novel minor histocompatibility antigens responsible for graft-versus-leukemia (GVL) effect on chronic myeloid leukemia: usefulness of determining the clonotype of T cells associated with GVL effect after donor leukocyte infusion. Int J Hematol 76(Suppl 1):274–276PubMedCrossRef

53.

Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D (1998) Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nature Medicine 4:328–332PubMedCrossRef

54.

Nicchitta CV (2003) Re-evaluating the role of heat-shock protein-peptide interactions in tumour immunity. Nat Rev Immunol 3:427–432PubMedCrossRef

55.

Ohashi K, Burkart V, Flohe S, Kolb H (2000) Cutting edge:heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J Immunol 164:558–561PubMed

56.

Panjwani N, Popova L, Febbraio M, Srivastava PK (2000) The CD36 scavenger receptor as a receptor for Gp96. Cell Stress Chaperones 5:391

57.

Pinilla-Ibarz J, Cathcart K, Korontsvit T, Soignet S, Bocchia M, Caggiano J, Lai L, Jimenez J, Kolitz J, Scheinberg DA (2000) Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses. Blood 95:1781–1787PubMed

58.

Princiotta MF, Finzi D, Qian SB, Gibbs J, Schuchmann S, Buttgereit F, Bennink JR, Yewdell, JW (2003) Quantitating protein synthesis, degradation, and endogenous antigen processing. Immunity 18:343–354PubMedCrossRef

59.

Prohaszka Z, Fust G (2004) Immunological aspects of heat-shock proteins-the optimum stress of life. Mol Immunol 41:29–44PubMedCrossRef

60.

Reits E, Griekspoor A, Neijssen J, Groothuis T, Jalink K, van Veelen P, Janssen H, Calafat J, Drijfhout JW, Neefjes J (2003) Peptide diffusion, protection, and degradation in nuclear and cytoplasmic compartments before antigen presentation by MHC class I. Immunity 18:97–108PubMedCrossRef

61.

Sawyers CL, Hochhaus A, Feldman E, Goldman JM, Miller CB, Ottmann OG, Schiffer CA, Talpaz M, Guilhot F, Deininger MW, Fischer T, O’Brien SG, Stone RM, Gambacorti-Passerini CB, Russell NH, Reiffers JJ, Shea TC, Chapuis B, Coutre S, Tura S, Morra E, Larson RA, Saven A, Peschel C, Gratwohl A, Mandelli F, Ben-Am M, Gathmann I, Capdeville R, Paquette RI, Druker BJ (2002) Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood 99:3530–3539PubMedCrossRef

62.

Somersan S, Larsson M, Fonteneau JF, Basu S, Srivastava P, Bhardwaj N (2001) Primary tumor tissue lysates are enriched in heat shock proteins and induce the maturation of human dendritic cells. J Immunol 167:4844–52PubMed

63.

Srivastava P (2002) Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annual Review of Immunology 20:395–425PubMedCrossRef

64.

Srivastava P (2002) Roles of heat-shock proteins in innate and adaptive immunity. Nature Reviews Immunology 2:185–194PubMedCrossRef

65.

Srivastava PK, DeLeo AB, Old LJ (1986) Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc Natl Acad Sci USA 83:3407–3411PubMedCrossRef

66.

Srivastava PK, Maki RG (1991) Stress-induced proteins in immune response to cancer. Curr Top Microbiol Immunol 167:109–123PubMed

67.

Srivastava PK, Udono H, Blachere NE, Li Z (1994) Heat shock proteins transfer peptides during antigen processing and CTL priming. Immunogenetics 39:93–98PubMedCrossRef

68.

Terme M, Tomasello E, Maruyama K, Crepineau F, Chaput N, Flament C, Marolleau JP, Angevin E, Wagner EF, Salomon B, Lemonnier FA, Wakasugi H, Colonna M, Vivier E, Zitvogel L (2004) IL-4 confers NK stimulatory capacity to murine dendritic cells: a signaling pathway involving KARAP/DAP12-triggering receptor expressed on myeloid cell 2 molecules. J Immunol 172:5957–5966PubMed

69.

Todryk SM, Melcher AA, Dalgleish AG, Vile RG (2000) Heat shock proteins refine the danger theory. Immunology 99:334–337PubMedCrossRef

70.

Udono H, Srivastava PK (1993) Heat shock protein 70-associated peptides elicit specific cancer immunity. Journal of Experimental Medicine 178:1391–1396PubMedCrossRef

71.

Udono H, Levey DL, Srivastava PK (1994) Cellular requirements for tumor-specific immunity elicited by heat shock proteins: tumor rejection antigen gp96 primes CD8+ T cells in vivo. Proc Natl Acad Sci U S A 91:3077–3081PubMedCrossRef

72.

Ullrich SJ, Robinson EA, Law LW, Willingham M, Appella E (1986) A mouse tumor-specific transplantation antigen is a heat shock-related protein. Proceedings of the National Academy of Sciences of the United States of America 83:3121–3125PubMedCrossRef

73.

Vabulas RM, Braedel S, Hilf N, Singh-Jasuja H, Herter S, Ahmad-Nejad P, Kirschning CJ, Da Costa C, Rammensee HG, Wagner H, Schild H (2002) The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway. J Biol Chem 277:20847–20853PubMedCrossRef

74.

Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I (1997) Immunosuppressive effects of apoptotic cells. Nature 390:350–351PubMedCrossRef

75.

Wallin RP, Lundqvist A, More SH, von Bonin A, Kiessling R, Ljunggren HG (2002) Heat-shock proteins as activators of the innate immune system. Trends Immunol 23:130–135PubMedCrossRef

76.

Wang H, Cheng F, Cuenca AG, Bhalla K, Sotomayor EM (2001) STI-571, a selective tyrosine kinase inhibitor, significantly enhances antigen presentation by bone marrow derived APCs: implications for immunotherapy of tumors-derived from antigen presenting cells, Paper presented at: The American Society of Hematology 43rd Annual Meeting (Orlando, Florida: American Society of Hematology)

77.

Yedavelli SP, Guo L, Daou ME, Srivastava PK, Mittelman A, Tiwari RK (1999) Preventive and therapeutic effect of tumor derived heat shock protein, gp96, in an experimental prostate cancer model. Int J Mol Med 4:243–248PubMed

78.

Zeng Y, Feng H, Graner MW, Katsanis E (2003) Tumor-derived, chaperone-rich cell lysate activates dendritic cells and elicits potent antitumor immunity. Blood 101:4485–4491PubMedCrossRef

79.

Zeng Y, Graner MW, Feng H, Li G, Katsanis E (2004) Imatinib mesylate effectively combines with chaperone-rich cell lysate-loaded dendritic cells to treat bcr-abl+ murine leukemia. International Journal of Cancer 110:251–259CrossRef

80.

Zeng Y, Graner MW, Thompson S, Marron M, Katsanis E (2004) Induction of BCR-ABL specific immunity following vaccination with chaperone rich cell lysates (CRCL) derived from BCR-ABL+ tumor cells. Blood 105:2016–2022PubMedCrossRef

Titel: Chaperone-rich cell lysates, immune activation and tumor vaccination
verfasst von: Yi Zeng
Michael W. Graner
Emmanuel Katsanis
Publikationsdatum: 01.03.2006
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 3/2006
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-005-0694-1

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Springer Medizin

Chaperone-rich cell lysates, immune activation and tumor vaccination

Abstract

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2006

Dendritic cells are essential for priming but inefficient for boosting antitumour immune response in an orthotopic murine glioma model

Dynamic control of lymphocyte trafficking by fever-range thermal stress

Effective induction of anti-melanoma immunity following genetic vaccination with synthetic mRNA coding for the fusion protein EGFP.TRP2

Heat shock proteins HSP70 and GP96: structural insights

Role Of Immature Myeloid Cells in Mechanisms of Immune Evasion In Cancer

Thermal stress-related modulation of tumor cell physiology and immune responses

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie