nach oben

Cancer Immunology, Immunotherapy

Erschienen in:

01.12.2009 | Original Article

Graft versus neuroblastoma reaction is efficiently elicited by allogeneic bone marrow transplantation through cytolytic activity in the absence of GVHD

verfasst von: Shifra Ash, Vered Gigi, Nadir Askenasy, Ina Fabian, Jerry Stein, Isaac Yaniv

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 12/2009

Einloggen, um Zugang zu erhalten

Abstract

Continuous efforts are dedicated to develop immunotherapeutic approaches to neuroblastoma (NB), a tumor that relapses at high rates following high-dose conventional cytotoxic therapy and autologous bone marrow cell (BMC) reconstitution. This study presents a series of transplant experiments aiming to evaluate the efficacy of allogeneic BMC transplantation. Neuro-2a cells were found to express low levels of class I major histocompatibility complex (MHC) antigens. While radiation and syngeneic bone marrow transplantation (BMT) reduced tumor growth (P < 0.001), allogeneic BMT further impaired subcutaneous development of Neuro-2a cells (P < 0.001). Allogeneic donor-derived T cells displayed direct cytotoxic activity against Neuro-2a in vitro, a mechanism of immune-mediated suppression of tumor growth. The proliferation of lymphocytes from congenic mice bearing subcutaneous tumors was inhibited by tumor lysate, suggesting that a soluble factor suppresses cytotoxic activity of syngeneic lymphocytes. However, the growth of Neuro-2a cells was impaired when implanted into chimeric mice at various times after syngeneic and allogeneic BMT. F1 (donor-host) splenocytes were infused attempting to foster immune reconstitution, however they engrafted transiently and had no effect on tumor growth. Taken together, these data indicate: (1) Neuro-2a cells express MHC antigens and immunogenic tumor associated antigens. (2) Allogeneic BMT is a significantly better platform to develop graft versus tumor (GVT) immunotherapy to NB as compared to syngeneic (autologous) immuno-hematopoietic reconstitution. (3) An effective GVT reaction in tumor bearing mice is primed by MHC disparity and targets tumor associated antigens.

Ladenstein R, Pötschger U, Hartman O, EBMT Paediatric Working Party et al (2008) 28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures. Bone Marrow Transplant 41(Suppl 2):S118–S127PubMedCrossRef

Kanold J, Yakouben K, Tchirkov A et al (2000) Long-term results of CD34(+) cell transplantation in children with neuroblastoma. Med Pediatr Oncol 35:1–7PubMedCrossRef

Burchill SA, Kinsey SE, Picton S et al (2001) Minimal residual disease at the time of peripheral blood stem cell harvest in patients with advanced neuroblastoma. Med Pediatr Oncol 36:213–219PubMedCrossRef

Bowman LC, Grossmann M, Rill D et al (1998) Interleukin-2 gene-modified allogeneic tumor cells for treatment of relapsed neuroblastoma. Hum Gene Ther 9:1303–1311PubMedCrossRef

Lode HN, Xiang R, Dreier T et al (1998) Natural killer cell-mediated eradication of neuroblastoma metastases to bone marrow by targeted interleukin-2 therapy. Blood 91:1706–1715PubMed

Haight AE, Bowman LC, Ng CY et al (2000) Humoral response to vaccination with interleukin-2-expressing allogeneic neuroblastoma cells after primary therapy. Med Pediatr Oncol 35:712–715PubMedCrossRef

Slavin S, Morecki S, Weiss L, Or R (2002) Donor lymphocyte infusion: the use of alloreactive and tumor-reactive lymphocytes for immunotherapy of malignant and nonmalignant diseases in conjunction with allogeneic stem cell transplantation. J Hematother Stem Cell Res 11:265–276PubMedCrossRef

Kanold J, Paillard C, Tchirkov A et al (2008) Allogeneic or haploidentical HSCT for refractory or relapsed solid tumors in children: toward a neuroblastoma model. Bone Marrow Transplant 42(Suppl 2):S25–S30PubMedCrossRef

Teshima T, Mach N, Hill GR et al (2001) Tumor cell vaccine elicits potent antitumor immunity after allogeneic T-cell-depleted bone marrow transplantation. Cancer Res 61:162–171PubMed

10.

Inoue M, Nakano T, Yoneda A et al (2003) Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haplo-identical bone marrow transplantation. Bone Marrow Transplant 32:103–106PubMedCrossRef

11.

Li JM, Waller EK (2004) Donor antigen-presenting cells regulate T-cell expansion and antitumor activity after allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 10:540–551PubMedCrossRef

12.

Hirayama M, Azuma E, Araki M et al (2006) Evidence of graft-versus-tumor effect in refractory metastatic neuroblastoma. Transplantation 82:142–144PubMedCrossRef

13.

Sykulev Y, Joo M, Vturina I et al (1996) Evidence that a single peptide-MHC complex on a target cell can elicit a cytolytic T cell response. Immunity 4:565–571PubMedCrossRef

14.

Main EK, Lampson LA, Hart MK et al (1985) Human neuroblastoma cell lines are susceptible to lysis by natural killer cells but not by cytotoxic T lymphocytes. J Immunol 135:242–246PubMed

15.

Coze C, Aalto-Setala K, Brenner M, Chiang Y (1995) Characteristics and immunomodulatory properties of human neuroblastoma cells after retrovirus-mediated gene transfer of the cytokine genes IL-2 and IFN-gamma. Transgenics 1:585–595

16.

Ponzoni M, Guarnaccia F, Corrias MV, Cornaglia-Ferraris P (1993) Uncoordinate induction and differential regulation of HLA class-I and class-II expression by gamma-interferon in differentiating human neuroblastoma cells. Int J Cancer 55:817–823PubMedCrossRef

17.

Murphy C, Nikodem D, Howcroft K et al (1996) Active repression of major histocompatibility complex class I genes in a human neuroblastoma cell line. J Biol Chem 271:30992–30999PubMedCrossRef

18.

Wolfl M, Jungbluth AA, Garrido F et al (2005) Expression of MHC class I, MHC class II, and cancer germline antigens in neuroblastoma. Cancer Immunol Immunother 54:400–406PubMedCrossRef

19.

Evans A, Main E, Zier K et al (1989) The effects of gamma interferon on the natural killer and tumor cells of children with neuroblastoma: a preliminary report. Cancer 64:1383–1387PubMedCrossRef

20.

Lampson LA, Whelan JP, Fisher CA (1985) HLA-A, B, C and beta 2-microglobulin are expressed weakly by human cells of neuronal origin, but can be induced in neuroblastoma cell lines by interferon. Prog Clin Biol Res 175:379–388PubMed

21.

Sugimoto T, Horii Y, Hino T et al (1989) Differential susceptibility of HLA class II antigens induced by gammainterferon in human neuroblastoma cell lines. Cancer Res 49:1824–1828PubMed

22.

Hock H, Dorsch M, Kunzendorf U et al (1993) Mechanisms of rejection induced by tumor cell-targeted gene transfer of interleukin 2, interleukin 4, interleukin 7, tumor necrosis factor, or interferon gamma. Proc Natl Acad Sci USA 90:2774–2778PubMedCrossRef

23.

Sadanaga N, Nagoshi M, Lederer JA et al (1999) Local secretion of IFN-gamma induces an antitumor response: comparison between T cells plus IL-2 and IFN-gamma transfected tumor cells. J Immunother 22:315–323PubMedCrossRef

24.

Katsanis E, Orchard PJ, Bausero MA et al (1994) Interleukin-2 gene transfer into murine neuroblastoma decreases tumorigenicity and enhances systemic immunity causing regression of preestablished retroperitoneal tumors. J Immunother 15:81–90CrossRef

25.

Bauer M, Reaman GH, Hank JA et al (1995) A phase II trial of human recombinant interleukin-2 administered as a 4-day continuous infusion for children with refractory neuroblastoma, non-Hodgkin’s lymphoma, sarcoma, renal cell carcinoma, and malignant melanoma. A Childrens Cancer Group study. Cancer 75:2959–2965PubMedCrossRef

26.

Bowman L, Grossmann M, Rill D et al (1998) IL-2 adenovector-transduced autologous tumor cells induce antitumor immune responses in patients with neuroblastoma. Blood 92:1941–1949PubMed

27.

Rousseau RF, Haight AE, Hirschmann-Jax C et al (2003) Local and systemic effects of an allogeneic tumor cell vaccine combining transgenic human lymphotactin with interleukin-2 in patients with advanced or refractory neuroblastoma. Blood 101:1718–1726PubMedCrossRef

28.

Pearl-Yafe M, Yolcu ES, Stein J et al (2007) Expression of Fas and Fas-ligand in donor hematopoietic stem and progenitor cells is dissociated from the sensitivity to apoptosis. Exp Hematol 35:1601–1612PubMedCrossRef

29.

Barker SE, Grosse SM, Siapati EK et al (2007) Immunotherapy for neuroblastoma using syngeneic fibroblasts transfected with IL-2 and IL-12. Br J Cancer 97:210–217PubMedCrossRef

30.

Christinck ER, Luscher MA, Barber BH, Williams DB (1991) Peptide binding to class I MHC on living cells and quantitation of complexes required for CTL lysis. Nature 352:67–70PubMedCrossRef

31.

Kageyama S, Tsomides TJ, Sykulev Y, Eisen HN (1995) Variations in the number of peptide-MHC class I complexes required to activate cytotoxic T cell responses. J Immunol 154:567–576PubMed

32.

Foss FM (2002) Immunologic mechanisms of antitumor activity. Semin Oncol 29:5–11PubMedCrossRef

33.

Saito M, Yu RK, Cheung NK (1985) Ganglioside GD2 specificity of monoclonal antibodies to human neuroblastoma cell. Biochem Biophys Res Commun 127:1–7PubMedCrossRef

34.

Croce M, Meazza R, Orengo AM et al (2008) Immunotherapy of neuroblastoma by an Interleukin-21-secreting cell vaccine involves survivin as antigen. Cancer Immunol Immunother 57:1625–1634PubMedCrossRef

35.

Sugimoto T, Tatsumi E, Kemshead JT et al (1984) Determination of cell surface membrane antigens common to both human neuroblastoma and leukemia-lymphoma cell lines by a panel of 38 monoclonal antibodies. J Natl Cancer Inst 73:51–57PubMed

36.

Schonmann SM, Iyer J, Laeng H et al (1986) Production and characterization of monoclonal antibodies against human neuroblastoma. Int J Cancer 37:255–262PubMedCrossRef

37.

Takagi S, Fujikawa K, Imai T et al (1995) Identification of a highly specific surface marker of T-cell acute lymphoblastic leukemia and neuroblastoma as a new member of the transmembrane 4 superfamily. Int J Cancer 61:706–715PubMedCrossRef

38.

Castriconi R, Dondero A, Augugliaro R et al (2004) Identification of 4Ig-B7–H3 as a neuroblastoma-associated molecule that exerts a protective role from an NK cell-mediated lysis. Proc Natl Acad Sci USA 101:12640–12645PubMedCrossRef

39.

Morisaki T, Matsumoto K, Onishi H et al (2003) Dendritic cell-based combined immunotherapy with autologous tumor-pulsed dendritic cell vaccine and activated T cells for cancer patients: rationale, current progress, and perspectives. Hum Cell 16:175–182PubMedCrossRef

40.

Redlinger RE Jr, Mailliard RB, Barksdale EM Jr (2004) Neuroblastoma and dendritic cell function. Semin Pediatr Surg 13:61–71PubMedCrossRef

41.

Fujii S (2008) Exploiting dendritic cells and natural killer T cells in immunotherapy against malignancies. Trends Immunol 29:242–249PubMedCrossRef

42.

Fernandez NC, Lozier A, Flament C et al (1999) Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med 5:405–411PubMedCrossRef

43.

Shimizu T, Berhanu A, Redlinger RE Jr et al (2001) Watkins S, Lotze MT, Barksdale EM Jr. Interleukin-12 transduced dendritic cells induce regression of established murine neuroblastoma. J Pediatr Surg 36:1285–1292PubMedCrossRef

44.

Castriconi R, Dondero A, Cilli M et al (2007) Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice. Cancer Immunol Immunother 56:1733–1742PubMedCrossRef

45.

Shurin GV, Shurin MR, Bykovskaia S et al (2001) Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. Cancer Res 61:363–369PubMed

46.

Redlinger RE Jr, Mailliard RB, Barksdale EM Jr (2003) Advanced neuroblastoma impairs dendritic cell function in adoptive immunotherapy. J Pediatr Surg 38:857–862PubMedCrossRef

47.

Yang L, Carbone DP (2004) Tumor-host immune interactions and dendritic cell dysfunction. Adv Cancer Res 92:13–27PubMedCrossRef

48.

Walker SR, Redlinger RE Jr, Barksdale EM Jr (2005) Neuroblastoma-induced inhibition of dendritic cell IL-12 production via abrogation of CD40 expression. J Pediatr Surg 40:244–250PubMedCrossRef

49.

Shurin GV, Gerein V, Lotze MT, Barksdale EM Jr (1998) Apoptosis induced in T cells by human neuroblastoma cells: role of Fas ligand. Nat Immun 16:263–274PubMedCrossRef

50.

Garrido F, Algarra I (2001) MHC antigens and tumor escape from immune surveillance. Adv Cancer Res 83:117–158PubMedCrossRef

51.

Slavin S, Aker M, Shapira MY et al (2003) Reduced-intensity conditioning for the treatment of malignant and life-threatening non-malignant disorders. Clin Transpl 275–282

52.

Stein J, Dini G, Yaniv I, Pediatric Diseases Working Party of the EBMT (2005) The hope and the reality of reduced intensity transplants in children with malignant diseases. Bone Marrow Transplant 35(Suppl 1):S39–S43PubMedCrossRef

Titel: Graft versus neuroblastoma reaction is efficiently elicited by allogeneic bone marrow transplantation through cytolytic activity in the absence of GVHD
verfasst von: Shifra Ash
Vered Gigi
Nadir Askenasy
Ina Fabian
Jerry Stein
Isaac Yaniv
Publikationsdatum: 01.12.2009
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 12/2009
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-009-0715-6

Neu im Fachgebiet Onkologie

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Springer Medizin

Graft versus neuroblastoma reaction is efficiently elicited by allogeneic bone marrow transplantation through cytolytic activity in the absence of GVHD

Abstract

Neu im Fachgebiet Onkologie

Umsetzung der POMGAT-Leitlinie läuft

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

Sind Frauen die fähigeren Ärzte?

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Onkologie

Springer Medizin

Abstract

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

Weitere Artikel der Ausgabe 12/2009

Use of CD40L immunoconjugates to overcome the defective immune response to vaccines for infections and cancer in the aged

Polymorphisms of pro-inflammatory genes and prostate cancer risk: a pharmacogenomic approach

The effect of aging on OX40 agonist-mediated cancer immunotherapy

Why do centenarians escape or postpone cancer? The role of IGF-1, inflammation and p53

Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts

Impact of aging on cancer immunity and immunotherapy

Neu im Fachgebiet Onkologie

Umsetzung der POMGAT-Leitlinie läuft

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

Sind Frauen die fähigeren Ärzte?

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Onkologie