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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 10/2003

01-10-2003 | Review

Optimizing dendritic cell–based anticancer immunotherapy: maturation state does have clinical impact

Authors: Dorian McIlroy, Marc Gregoire

Published in: Cancer Immunology, Immunotherapy | Issue 10/2003

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Abstract

Tumour immunotherapy using dendritic cells (DCs) is a new therapeutic approach, which has been applied to a variety of different cancers over the last 5 years. Here we discuss the clinical results of these trials in relation to the different protocols used to generate DCs, and in particular the effect that DC maturation state has had on clinical responses. In ten different melanoma trials a total of 167 patients have been treated, resulting in 9 complete tumour regressions, 24 partial regressions, 26 patients with stable disease, and 108 with progressive disease. Favourable response, defined as any outcome other than progressive disease, was not associated with previous chemotherapy, but was significantly correlated (p<0.001) with the addition of TNF-α for the maturation of DCs in vitro. Hence DC maturation state has had an impact on clinical responses to therapy. However, TNF-α is not the only molecule capable of inducing DC maturation, and strategies for improving clinical responses by optimizing DC maturation are discussed.
Literature
1.
Rosenberg SA (2001) Progress in human tumour immunology and immunotherapy. Nature 411:380–384PubMed
2.
Press OW, Leonard JP, Coiffier B, Levy R, Timmerman J (2001) Immunotherapy of Non-Hodgkin's lymphomas. Hematology (Am Soc Hematol Educ Program):221–240
3.
Vermorken JB, Claessen AM, van Tinteren H, Gall HE, Ezinga R, Meijer S, Scheper RJ, Meijer CJ, Bloemena E, Ransom JH, Hanna MG Jr, Pinedo HM (1999) Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial. Lancet 353:345–350PubMed
4.
Sondak VK, Liu PY, Tuthill RJ, Kempf RA, Unger JM, Sosman JA, Thompson JA, Weiss GR, Redman BG, Jakowatz JG, Noyes RD, Flaherty LE (2002) Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: overall results of a randomized trial of the Southwest Oncology Group. J Clin Oncol 20:2058–2066
5.
Dillman RO, Beutel LD, Barth NM, de Leon C, O'Connor AA, DePriest C, Nayak SK (2002) Irradiated cells from autologous tumor cell lines as patient-specific vaccine therapy in 125 patients with metastatic cancer: induction of delayed-type hypersensitivity to autologous tumor is associated with improved survival. Cancer Biother Radiopharm 17:51–66CrossRefPubMed
6.
Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Restifo NP, Dudley ME, Schwarz SL, Spiess PJ, Wunderlich JR, Parkhurst MR, Kawakami Y, Seipp CA, Einhorn JH, White DE (1998) Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med 4:321–327PubMed
7.
Wang F, Bade E, Kuniyoshi C, Spears L, Jeffery G, Marty V, Groshen S, Weber J, Slingluff CL Jr, Yamshchikov G, Neese P, Galavotti H, Eastham S, Engelhard VH, Kittlesen D, Deacon D, Hibbitts S, Grosh WW, Petroni G, Cohen R, Wiernasz C, Patterson JW, Conway BP, Ross WG (1999) Phase I trial of a MART-1 peptide vaccine with incomplete Freund's adjuvant for resected high-risk melanoma. Clin Cancer Res 5:2756–2765PubMed
8.
Slingluff CL Jr, Yamshchikov G, Neese P, Galavotti H, Eastham S, Engelhard VH, Kittlesen D, Deacon D, Hibbitts S, Grosh WW, Petroni G, Cohen R, Wiernasz C, Patterson JW, Conway BP, Ross WG (2001) Phase I trial of a melanoma vaccine with gp100(280–288) peptide and tetanus helper peptide in adjuvant: immunologic and clinical outcomes. Clin Cancer Res 7:3012–3024
9.
Pacanowski J, Kahi S, Baillet M, Lebon P, Deveau C, Goujard C, Meyer L, Oksenhendler E, Sinet M, Hosmalin A (2001) Reduced blood CD123+ (lymphoid) and CD11c+ (myeloid) dendritic cell numbers in primary HIV-1 infection. Blood 98:3016–3021CrossRefPubMed
10.
Grassi F, Dezutter-Dambuyant C, McIlroy D, Jacquet C, Yoneda K, Imamura S, Boumsell L, Schmitt D, Autran B, Debre P, Hosmalin A (1998) Monocyte-derived dendritic cells have a phenotype comparable to that of dermal dendritic cells and display ultrastructural granules distinct from Birbeck granules. J Leukoc Biol 64:484–493PubMed
11.
Caux C, Dezutter-Dambuyant C, Schmitt D, Banchereau J (1992) GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 360:258–261PubMed
12.
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
13.
De Jong EC, Vieira PL, Kalinski P, Schuitemaker JH, Tanaka Y, Wierenga EA, Yazdanbakhsh M, Kapsenberg ML (2002) Microbial compounds selectively induce Th1 cell-promoting or Th2 cell-promoting dendritic cells in vitro with diverse th cell-polarizing signals. J Immunol 168:1704–1709PubMed
14.
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
15.
Gilliet M, Liu YJ (2002) Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J Exp Med 195:695–704CrossRefPubMed
16.
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
17.
Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193:233–238PubMed
18.
Chen Z, Dehm S, Bonham K, Kamencic H, Juurlink B, Zhang X, Gordon JR, Xiang J (2001) DNA array and biological characterization of the impact of the maturation status of mouse dendritic cells on their phenotype and antitumor vaccination efficacy. Cell Immunol 214:60–71CrossRefPubMed
19.
Timmerman JM, Czerwinski DK, Davis TA, Hsu FJ, Benike C, Hao ZM, Taidi B, Rajapaksa R, Caspar CB, Okada CY, van Beckhoven A, Liles TM, Engleman EG, Levy R (2002) Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients. Blood 99:1517–1526CrossRefPubMed
20.
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 98:8809–8814PubMed
21.
Mackensen A, Herbst B, Chen JL, Kohler G, Noppen C, Herr W, Spagnoli GC, Cerundolo V, Lindemann A (2000) Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. Int J Cancer 86:385–932PubMed
22.
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 4:328–332PubMed
23.
Thurner B, Haendle I, Roder C, Dieckmann D, Keikavoussi P, Jonuleit H, Bender A, Maczek C, Schreiner D, von den Driesch P, Brocker EB, Steinman RM, Enk A, Kampgen E, Schuler G (1999) Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med 190:1669–1678PubMed
24.
Schuler-Thurner B, Schultz ES, Berger TG, Weinlich G, Ebner S, Woerl P, Bender A, Feuerstein B, Fritsch PO, Romani N, Schuler G (2002) Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med 195:1279–1288CrossRefPubMed
25.
Panelli MC, Wunderlich J, Jeffries J, Wang E, Mixon A, Rosenberg SA,Marincola FM (2000) Phase I study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. J Immunother 23:487–498PubMed
26.
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 93:243–251PubMed
27.
Lau R, Wang F, Jeffery G, Marty V, Kuniyoshi J, Bade E, Ryback ME, Weber J (2001) Phase I trial of intravenous peptide-pulsed dendritic cells in patients with metastatic melanoma. J Immunother 24:66–78
28.
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
29.
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
30.
Murphy GP, Tjoa BA, Simmons SJ, Jarisch J, Bowes VA, Ragde H, Rogers M, Elgamal A, Kenny GM, Cobb OE, Ireton RC, Troychak MJ, Salgaller ML, Boynton AL (1999) Infusion of dendritic cells pulsed with HLA-A2-specific prostate-specific membrane antigen peptides: a phase II prostate cancer vaccine trial involving patients with hormone-refractory metastatic disease. Prostate 38:73–78CrossRefPubMed
31.
Morse MA, Deng Y, Coleman D, Hull S, Kitrell-Fisher E, Nair S, Schlom J, Ryback ME, Lyerly HK (1999) A phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. Clin Cancer Res 5:1331–1338PubMed
32.
Sadanaga N, Nagashima H, Mashino K, Tahara K, Yamaguchi H, Ohta M, Fujie T, Tanaka F, Inoue H, Takesako K, Akiyoshi T, Mori M (2001) Dendritic cell vaccination with MAGE peptide is a novel therapeutic approach for gastrointestinal carcinomas. Clin Cancer Res 7:2277–2284PubMed
33.
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
34.
Lin CL, Lo WF, Lee TH, Ren Y, Hwang SL, Cheng YF, Chen CL, Chang YS, Lee SP, Rickinson AB, Tam PK (2002) Immunization with Epstein-Barr Virus (EBV. peptide-pulsed dendritic cells induces functional CD8+ T-cell immunity and may lead to tumor regression in patients with EBV-positive nasopharyngeal carcinoma. Cancer Res 62:6952–6958PubMed
35.
Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, Muller CA, Becker V, Gross AJ, Hemmerlein B, Kanz L, Muller GA, Ringert RH (2000) Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat Med 6:332–336PubMed
36.
Bostanci A, Vogel G (2002) Research misconduct: German inquiry finds flaws, not fraud. Science 298:1531–1533CrossRef
37.
Schiermeier Q (2002) Cancer researcher found guilty of negligence. Nature 420:258CrossRef
38.
Helmbach H, Kern MA, Rossmann E, Renz K, Kissel C, Gschwendt B, Schadendorf D (2002) Drug resistance towards etoposide and cisplatin in human melanoma cells is associated with drug-dependent apoptosis deficiency. J Invest Dermatol 118:923–932CrossRefPubMed
39.
Soengas MS, Capodieci P, Polsky D, Mora J, Esteller M, Opitz-Araya X, McCombie R, Herman JG, Gerald WL, Lazebnik YA, Cordon-Cardo C, Lowe SW (2001) Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature 409:207–211
40.
Grossman D, Altieri DC (2001) Drug resistance in melanoma: mechanisms, apoptosis, and new potential therapeutic targets. Cancer Metastasis Rev 20:3-11CrossRefPubMed
41.
Schuler-Thurner B, Dieckmann D, Keikavoussi P, Bender A, Maczek C, Jonuleit H, Roder C, Haendle I, Leisgang W, Dunbar R, Cerundolo V, von Den Driesch P, Knop J, Brocker EB, Enk A, Kampgen E, Schuler G (2000) Mage-3 and influenza-matrix peptide-specific cytotoxic T cells are inducible in terminal stage HLA-A2.1+ melanoma patients by mature monocyte-derived dendritic cells. J Immunol 165:3492–3496PubMed
42.
Huang Q, Liu D, Majewski P, Schulte LC, Korn JM, Young RA, Lander ES, Hacohen N (2001) The plasticity of dendritic cell responses to pathogens and their components. Science 294:870–875CrossRefPubMed
43.
Granucci F, Vizzardelli C, Virzi E, Rescigno M, Ricciardi-Castagnoli P (2001) Transcriptional reprogramming of dendritic cells by differentiation stimuli. Eur J Immunol 31:2539–2546CrossRefPubMed
44.
De Vries IJ, Krooshoop DJ, Scharenborg NM, Lesterhuis WJ, Diepstra JH, Van Muijen GN, Strijk SP, Ruers TJ, Boerman OC, Oyen WJ, Adema GJ, Punt CJ, Figdor CG (2003) Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res 63:12–17PubMed
45.
Jonuleit H, Kuhn U, Muller G, Steinbrink K, Paragnik L, Schmitt E, Knop J, Enk AH (1997) Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol 27:3135–3142PubMed
46.
Luft T, Jefford M, Luetjens P, Toy T, Hochrein H, Masterman KA, Maliszewski C, Shortman K, Cebon J, Maraskovsky E (2002) Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E(2) regulates the migratory capacity of specific DC subsets. Blood 100:1362–1372CrossRefPubMed
47.
Scandella E, Men Y, Gillessen S, Forster R, Groettrup M (2002) Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. Blood 100:1354–1361CrossRefPubMed
48.
Kalinski P, Schuitemaker JH, Hilkens CM, Kapsenberg ML (1998) Prostaglandin E2 induces the final maturation of IL-12-deficient CD1a+CD83+ dendritic cells: the levels of IL-12 are determined during the final dendritic cell maturation and are resistant to further modulation. J Immunol 161:2804–2809PubMed
49.
Spisek R, Bretaudeau L, Barbieux I, Meflah K, Gregoire M (2001) Standardized generation of fully mature p70 IL-12 secreting monocyte-derived dendritic cells for clinical use. Cancer Immunol Immunother 50:417–427CrossRefPubMed
50.
Spisek R, Bougras G, Ebstein F, Masse D, Barbieux I, Meflah K, McIlroy D, Gregoire M (2003) Transient exposure of dendritic cells to maturation stimuli is sufficient to induce complete phenotypic maturation while preserving dendritic cell capacity to respond to subsequent restimulation. Cancer Immunol Immunother (in press)
51.
Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr, Mellor AL (2002) Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297:1867–1870CrossRefPubMed
52.
Terness P, Bauer TM, Rose L, Dufter C, Watzlik A, Simon H, Opelz G (2002) Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J Exp Med 196:447–457CrossRefPubMed
53.
Akbari O, Freeman GJ, Meyer EH, Greenfield EA, Chang TT, Sharpe AH, Berry G, DeKruyff RH, Umetsu DT (2002) Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Med 8:1024–1032CrossRefPubMed
54.
Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson KL, Daniel B, Zimmerman MC, David O, Burow M, Gordon A, Dhurandhar N, Myers L, Berggren R, Hemminski A, Alvarez RD, Emilie D, Curiel DT, Chen L, Zou W (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9:562–567
Metadata
Title
Optimizing dendritic cell–based anticancer immunotherapy: maturation state does have clinical impact
Authors
Dorian McIlroy
Marc Gregoire
Publication date
01-10-2003
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 10/2003
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-003-0414-7

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