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01.07.2006 | Original Article

Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate

verfasst von: Margarita Salcedo, Nadège Bercovici, Rachel Taylor, Pierre Vereecken, Séverine Massicard, Dominique Duriau, Frédérique Vernel-Pauillac, Aurélie Boyer, Véronique Baron-Bodo, Eric Mallard, Jacques Bartholeyns, Béatrice Goxe, Nathalie Latour, Sophie Leroy, Didier Prigent, Philippe Martiat, François Sales, Marianne Laporte, Catherine Bruyns, Jean-Loup Romet-Lemonne, Jean-Pierre Abastado, Frédéric Lehmann, Thierry Velu

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2006

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Abstract

The aim of the present phase I/II study was to evaluate the safety, immune responses and clinical activity of a vaccine based on autologous dendritic cells (DC) loaded with an allogeneic tumor cell lysate in advanced melanoma patients. DC derived from monocytes were generated in serum-free medium containing GM-CSF and IL-13 according to Good Manufacturing Practices. Fifteen patients with metastatic melanoma (stage III or IV) received four subcutaneous, intradermal, and intranodal vaccinations of both DC loaded with tumor cell lysate and DC loaded with hepatitis B surface protein (HBs) and/or tetanus toxoid (TT). No grade 3 or 4 adverse events related to the vaccination were observed. Enhanced immunity to the allogeneic tumor cell lysate and to TAA-derived peptides were documented, as well as immune responses to HBs/TT antigens. Four out of nine patients who received the full treatment survived for more than 20 months. Two patients showed signs of clinical response and received 3 additional doses of vaccine: one patient showed regression of in-transit metastases leading to complete remission. Eighteen months later, the patient was still free of disease. The second patient experienced stabilization of lung metastases for approximately 10 months. Overall, our results show that vaccination with DC loaded with an allogeneic melanoma cell lysate was feasible in large-scale and well-tolerated in this group of advanced melanoma patients. Immune responses to tumor-related antigens documented in some treated patients support further investigations to optimize the vaccine formulation.

Hartmann E, Wollenberg B, Rothenfusser S, Wagner M, Wellisch D, Mack B, Giese T, Gires O, Endres S, Hartmann G (2003) Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Res 63:6478–6487PubMed

Della Bella S, Gennaro M, Vaccari M, Ferraris C, Nicola S, Riva A, Clerici M, Greco M, Villa ML (2003) Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer 89:1463–1472CrossRefPubMed

Huang A, Gilmour JW, Imami N, Amjadi P, Henderson DC, Allen-Mersh TG (2003) Increased serum transforming growth factor-beta1 in human colorectal cancer correlates with reduced circulating dendritic cells and increased colonic Langerhans cell infiltration. Clin Exp Immunol 134:270–278CrossRefPubMed

Lee JR, Dalton RR, Messina JL, Sharma MD, Smith DM, Burgess RE, Mazzella F, Antonia SJ, Mellor AL, Munn DH (2003) Pattern of recruitment of immunoregulatory antigen-presenting cells in malignant melanoma. Lab Invest 83:1457–1466CrossRefPubMed

Schuler G, Schuler-Thurner B, Steinman RM (2003) The use of dendritic cells in cancer immunotherapy. Curr Opin Immunol 15:138–147CrossRefPubMed

Cranmer LD, Trevor KT, Hersh EM (2004) Clinical applications of dendritic cell vaccination in the treatment of cancer. Cancer Immunol Immunother 53:275–306CrossRefPubMed

Svane IM, Soot ML, Buus S, Johnsen HE (2003) Clinical application of dendritic cells in cancer vaccination therapy. Apmis 111:818–834CrossRefPubMed

Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, Pineiro L, Steinman R, Fay J (2001) Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res 61:6451–6458PubMed

Fong L, Hou Y, Rivas A, Benike C, Yuen A, Fisher GA, Davis MM, Engleman EG (2001) Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc Natl Acad Sci USA 98:8809–8814PubMedCrossRef

10.

Lonchay C, van der Bruggen P, Connerotte T, Hanagiri T, Coulie P, Colau D, Lucas S, Van Pel A, Thielemans K, van Baren N, Boon T (2004) Correlation between tumor regression and T cell responses in melanoma patients vaccinated with a MAGE antigen. Proc Natl Acad Sci USA 101(Suppl 2):14631–14638PubMedCrossRef

11.

Riker A, Cormier J, Panelli M, Kammula U, Wang E, Abati A, Fetsch P, Lee KH, Steinberg S, Rosenberg S, Marincola F (1999) Immune selection after antigen-specific immunotherapy of melanoma. Surgery 126:112–120PubMed

12.

Brossart P, Bevan MJ (1997) Presentation of exogenous protein antigens on major histocompatibility complex class I molecules by dendritic cells: pathway of presentation and regulation by cytokines. Blood 90:1594–1599PubMed

13.

Shen Z, Reznikoff G, Dranoff G, Rock KL (1997) Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J Immunol 158:2723–2730PubMed

14.

Fields RC, Shimizu K, Mule JJ (1998) Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responses in vitro and in vivo. Proc Natl Acad Sci USA 95:9482–9487PubMedCrossRef

15.

Chang AE, Redman BG, Whitfield JR, Nickoloff BJ, Braun TM, Lee PP, Geiger JD, Mule JJ (2002) A phase I trial of tumor lysate-pulsed dendritic cells in the treatment of advanced cancer. Clin Cancer Res 8:1021–1032PubMed

16.

Maier T, Tun-Kyi A, Tassis A, Jungius KP, Burg G, Dummer R, Nestle FO (2003) Vaccination of patients with cutaneous T-cell lymphoma using intranodal injection of autologous tumor-lysate-pulsed dendritic cells. Blood 102:2338–2344CrossRefPubMed

17.

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. Nat Med 4:328–332CrossRefPubMed

18.

Goxe B, Latour N, Chokri M, Abastado JP, Salcedo M (2000) Simplified method to generate large quantities of dendritic cells suitable for clinical applications. Immunol Invest 29:319–336PubMed

19.

Boccaccio C, Jacod S, Kaiser A, Boyer A, Abastado JP, Nardin A (2002) Identification of a clinical-grade maturation factor for dendritic cells. J Immunother 25:88–96CrossRefPubMed

20.

Bercovici N, Givan AL, Waugh MG, Fisher JL, Vernel-Pauillac F, Ernstoff MS, Abastado JP, Wallace PK (2003) Multiparameter precursor analysis of T-cell responses to antigen. J Immunol Methods 276:5–17CrossRefPubMed

21.

de Vries IJ, Lesterhuis WJ, Scharenborg NM, Engelen LP, Ruiter DJ, Gerritsen MJ, Croockewit S, Britten CM, Torensma R, Adema GJ, Figdor CG, Punt CJ (2003) Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients. Clin Cancer Res 9:5091–5100PubMed

22.

Geiger JD, Hutchinson RJ, Hohenkirk LF, McKenna EA, Yanik GA, Levine JE, Chang AE, Braun TM, Mule JJ (2001) Vaccination of pediatric solid tumor patients with tumor lysate-pulsed dendritic cells can expand specific T cells and mediate tumor regression. Cancer Res 61:8513–8519PubMed

23.

Jonuleit H, Giesecke-Tuettenberg A, Tuting T, Thurner-Schuler B, Stuge TB, Paragnik L, Kandemir A, Lee PP, Schuler G, Knop J, Enk AH (2001) A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer 93:243–251CrossRefPubMed

24.

Chakraborty NG, Sporn JR, Tortora AF, Kurtzman SH, Yamase H, Ergin MT, Mukherji B (1998) Immunization with a tumor-cell-lysate-loaded autologous-antigen-presenting-cell-based vaccine in melanoma. Cancer Immunol Immunother 47:58–64CrossRefPubMed

25.

Soiffer R, Lynch T, Mihm M, Jung K, Rhuda C, Schmollinger JC, Hodi FS, Liebster L, Lam P, Mentzer S, Singer S, Tanabe KK, Cosimi AB, Duda R, Sober A, Bhan A, Daley J, Neuberg D, Parry G, Rokovich J, Richards L, Drayer J, Berns A, Clift S, Cohen LK, Mulligan RC, Dranoff G (1998) Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci USA 95:13141–13146PubMedCrossRef

26.

Mitchell MS, Kan-Mitchell J, Kempf RA, Harel W, Shau HY, Lind S (1988) Active specific immunotherapy for melanoma: phase I trial of allogeneic lysates and a novel adjuvant. Cancer Res 48:5883–5893PubMed

27.

Soiffer R, Hodi FS, Haluska F, Jung K, Gillessen S, Singer S, Tanabe K, Duda R, Mentzer S, Jaklitsch M, Bueno R, Clift S, Hardy S, Neuberg D, Mulligan R, Webb I, Mihm M, Dranoff G (2003) Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. J Clin Oncol 21:3343–3350CrossRefPubMed

28.

Griffioen M, Borghi M, Schrier PI, Osanto S, Schadendorf D (2004) Analysis of T-cell responses in metastatic melanoma patients vaccinated with dendritic cells pulsed with tumor lysates. Cancer Immunol Immunother 53:715–722CrossRefPubMed

29.

Hernando JJ, Park TW, Kubler K, Offergeld R, Schlebusch H, Bauknecht T (2002) Vaccination with autologous tumour antigen-pulsed dendritic cells in advanced gynaecological malignancies: clinical and immunological evaluation of a phase I trial. Cancer Immunol Immunother 51:45–52CrossRefPubMed

30.

Mitchell MS, Kan-Mitchell J, Morrow PR, Darrah D, Jones VE, Mescher MF (2004) Phase I trial of large multivalent immunogen derived from melanoma lysates in patients with disseminated melanoma. Clin Cancer Res 10:76–83CrossRefPubMed

31.

Vilella R, Benitez D, Mila J, Lozano M, Vilana R, Pomes J, Tomas X, Costa J, Vilalta A, Malvehy J, Puig S, Mellado B, Marti R, Castel T (2004) Pilot study of treatment of biochemotherapy-refractory stage IV melanoma patients with autologous dendritic cells pulsed with a heterologous melanoma cell line lysate. Cancer Immunol Immunother 53:651–658CrossRefPubMed

32.

Yu JS, Liu G, Ying H, Yong WH, Black KL, Wheeler CJ (2004) Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res 64:4973–4979CrossRefPubMed

33.

Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5:263–274CrossRefPubMed

34.

Berard F, Blanco P, Davoust J, Neidhart-Berard EM, Nouri-Shirazi M, Taquet N, Rimoldi D, Cerottini JC, Banchereau J, Palucka AK (2000) Cross-priming of naive CD8 T cells against melanoma antigens using dendritic cells loaded with killed allogeneic melanoma cells. J Exp Med 192:1535–1544CrossRefPubMed

35.

Mitchell MS, Harel W, Groshen S (1992) Association of HLA phenotype with response to active specific immunotherapy of melanoma. J Clin Oncol 10:1158–1164PubMed

36.

Kaiser A, Bercovici N, Abastado JP, Nardin A (2003) Naive CD8+ T cell recruitment and proliferation are dependent on stage of dendritic cell maturation. Eur J Immunol 33:162–171CrossRefPubMed

37.

Adema GJ, de Vries IJ, Punt CJ, Figdor CG (2005) Migration of dendritic cell based cancer vaccines: in vivo veritas? Curr Opin Immunol 17:170–174CrossRefPubMed

38.

Nestle FO, Farkas A, Conrad C (2005) Dendritic-cell-based therapeutic vaccination against cancer. Curr Opin Immunol 17:163–169CrossRefPubMed

39.

Langenkamp A, Messi M, Lanzavecchia A, Sallusto F (2000) Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nat Immunol 1:311–316CrossRefPubMed

40.

Albert ML, Jegathesan M, Darnell RB (2001) Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells. Nat Immunol 2:1010–1017CrossRefPubMed

41.

Ribas A, Glaspy JA, Lee Y, Dissette VB, Seja E, Vu HT, Tchekmedyian NS, Oseguera D, Comin-Anduix B, Wargo JA, Amarnani SN, McBride WH, Economou JS, Butterfield LH (2004) Role of dendritic cell phenotype, determinant spreading, and negative costimulatory blockade in dendritic cell-based melanoma immunotherapy. J Immunother 27:354–367CrossRefPubMed

42.

Smithers M, O’Connell K, MacFadyen S, Chambers M, Greenwood K, Boyce A, Abdul-Jabbar I, Barker K, Grimmett K, Walpole E, Thomas R (2003) Clinical response after intradermal immature dendritic cell vaccination in metastatic melanoma is associated with immune response to particulate antigen. Cancer Immunol Immunother 52:41–52PubMed

43.

Su Z, Dannull J, Heiser A, Yancey D, Pruitt S, Madden J, Coleman D, Niedzwiecki D, Gilboa E, Vieweg J (2003) Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. Cancer Res 63:2127–2133PubMed

44.

Barratt-Boyes SM, Zimmer MI, Harshyne LA, Meyer EM, Watkins SC, Capuano S 3rd, Murphey-Corb M, Falo LD Jr, Donnenberg AD (2000) Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines. J Immunol 164:2487–2495PubMed

45.

Mileshkin LR, Wall DM, Loveland BE, Thompson M, Coverdale J, Wong J, Xing PX, Taylor RR, Hicks RJ, Prince HM (2004) A Study of in vivo tracking of MUC-1 pulsed dendritic cells in patients with multiple myeloma. In: 19th Annual SBT meeting 2004, San-Francisco, CA

Titel: Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate
verfasst von: Margarita Salcedo
Nadège Bercovici
Rachel Taylor
Pierre Vereecken
Séverine Massicard
Dominique Duriau
Frédérique Vernel-Pauillac
Aurélie Boyer
Véronique Baron-Bodo
Eric Mallard
Jacques Bartholeyns
Béatrice Goxe
Nathalie Latour
Sophie Leroy
Didier Prigent
Philippe Martiat
François Sales
Marianne Laporte
Catherine Bruyns
Jean-Loup Romet-Lemonne
Jean-Pierre Abastado
Frédéric Lehmann
Thierry Velu
Publikationsdatum: 01.07.2006
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 7/2006
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-005-0078-6

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Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate

Abstract

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