nach oben

Cancer Immunology, Immunotherapy

Erschienen in:

01.09.2009 | Original Article

BCR/ABL-specific CD8⁺ T cells can be detected from CML patients, but are only expanded from healthy donors

verfasst von: Sylvie Rusakiewicz, Alejandro Madrigal, Paul Travers, Anthony I. Dodi

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 9/2009

Einloggen, um Zugang zu erhalten

Abstract

The BCR/ABL p210 fusion protein has long been considered an ideal target antigen for the development of immunotherapeutic strategies in chronic myeloid leukaemia (CML) due to its central role in malignant transformation and to its unique novel amino acid sequence solely expressed in leukaemia cells. However, the feasibility to expand BCR-ABL-specific T cells remains still controversial. Using BCR/ABL peptide/MHC tetramers, significantly higher frequencies of tetramer positive cells were detected in the peripheral blood of HLA-A*0301 (mean 0.38%) and HLA-B*0801 (mean 0.28%) CML patients than in healthy donors (P = 0.0025 and 0.0026, respectively). However, following stimulation with autologous peptide-pulsed DCs, BCR/ABL-specific T cells were only expanded from some healthy donors, suggesting that CML patients may have a specific immune deficit with respect to the BCR/ABL antigen.

Altman JD, Moss PA, Goulder PJ, Barouch DH, McHeyzer-Williams MG, Bell JI, McMichael AJ, Davis MM (1996) Phenotypic analysis of antigen-specific T lymphocytes. Science 274(5284):94–96PubMedCrossRef

Bertazzoli C, Marchesi E, Passoni L, Barni R, Ravagnani F, Lombardo C, Corneo GM, Pioltelli P, Pogliani E, Gambacorti-Passerini C (2000) Differential recognition of a BCR/ABL peptide by lymphocytes from normal donors and chronic myeloid leukemia patients. Clin Cancer Res 6(5):1931–1935PubMed

Bocchia M, Wentworth PA, Southwood S, Sidney J, McGraw K, Scheinberg DA, Sette A (1995) Specific binding of leukemia oncogene fusion protein peptides to HLA class I molecules. Blood 85(10):2680–2684PubMed

Bocchia M, Gentili S, Abruzzese E, Fanelli A, Iuliano F, Tabilio A, Amabile M, Forconi F, Gozzetti A, Raspadori D, Amadori S, Lauria F (2005) Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial. Lancet 365(9460):657–662PubMed

Bosch GJ, Joosten AM, Kessler JH, Melief CJ, 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(9):3522–3527PubMed

Butt NM, Wang L, Abu-Eisha HM, Christmas SE, Clark RE (2004) BCR-ABL-specific T cells can be detected in healthy donors and in chronic myeloid leukemia patients following allogeneic stem cell transplantation. Blood 103(8):3245PubMedCrossRef

Butt NM, Rojas JM, Wang L, Christmas SE, Abu-Eisha HM, Clark RE (2005) Circulating bcr-abl-specific CD8+ T cells in chronic myeloid leukemia patients and healthy subjects. Haematologica 90(10):1315–1323PubMed

Buzyn A, Ostankovitch M, Zerbib A, Kemula M, Connan F, Varet B, Guillet JG, Choppin J (1997) Peptides derived from the whole sequence of BCR-ABL bind to several class I molecules allowing specific induction of human cytotoxic T lymphocytes. Eur J Immunol 27(8):2066–2072PubMedCrossRef

Cathcart K, Pinilla-Ibarz J, Korontsvit T, Schwartz J, Zakhaleva V, Papadopoulos EB, Scheinberg DA (2004) A multivalent bcr-abl fusion peptide vaccination trial in patients with chronic myeloid leukemia. Blood 103(3):1037–1042PubMedCrossRef

10.

Choudhury A, Gajewski JL, Liang JC, Popat U, Claxton DF, Kliche KO, Andreeff M, Champlin RE (1997) Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxicity against Philadelphia chromosome-positive chronic myelogenous leukemia. Blood 89(4):1133–1142PubMed

11.

Clark RE, Dodi IA, Hill SC, Lill JR, Aubert G, Macintyre AR, Rojas J, Bourdon A, Bonner PL, Wang L, Christmas SE, Travers PJ, Creaser CS, Rees RC, Madrigal JA (2001) Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein. Blood 98(10):2887–2893PubMedCrossRef

12.

Deininger MW, Goldman JM, Melo JV (2000) The molecular biology of chronic myeloid leukemia. Blood 96(10):3343–3356PubMed

13.

Dong R, Cwynarski K, Entwistle A, Marelli-Berg F, Dazzi F, Simpson E, Goldman JM, Melo JV, Lechler RI, Bellantuono I, Ridley A, Lombardi G (2003) Dendritic cells from CML patients have altered actin organization, reduced antigen processing, and impaired migration. Blood 101(9):3560–3567PubMedCrossRef

14.

Gannage M, Abel M, Michallet AS, Delluc S, Lambert M, Giraudier S, Kratzer R, Niedermann G, Saveanu L, Guilhot F, Camoin L, Varet B, Buzyn A, Caillat-Zucman S (2005) Ex vivo characterization of multiepitopic tumor-specific CD8 T cells in patients with chronic myeloid leukemia: implications for vaccine development and adoptive cellular immunotherapy. J Immunol 174(12):8210–8218PubMed

15.

Greco G, Fruci D, Accapezzato D, Barnaba V, Nisini R, Alimena G, Montefusco E, Vigneti E, Butler R, Tanigaki N, Tosi R (1996) Two brc-abl junction peptides bind HLA-A3 molecules and allow specific induction of human cytotoxic T lymphocytes. Leukemia 10(4):693–699PubMed

16.

Grunebach F, Mirakaj V, Muller MR, Brummendorf T, Brossart P (2006) BCR-ABL is not an immunodominant antigen in chronic myelogenous leukemia. Cancer Res 66(11):5892–5900PubMedCrossRef

17.

Kessler JH, Bres-Vloemans SA, van Veelen PA, de Ru A, Huijbers IJ, Camps M, Mulder A, Offringa R, Drijfhout JW, Leeksma OC, Ossendorp F, Melief CJ (2006) BCR-ABL fusion regions as a source of multiple leukemia-specific CD8+ T-cell epitopes. Leukemia 20(10):1738–1750PubMedCrossRef

18.

Mannering SI, McKenzie JL, Fearnley DB, Hart DN (1997) HLA-DR1-restricted bcr-abl (b3a2)-specific CD4+ T lymphocytes respond to dendritic cells pulsed with b3a2 peptide and antigen-presenting cells exposed to b3a2 containing cell lysates. Blood 90(1):290–297PubMed

19.

Nieda M, Nicol A, Kikuchi A, Kashiwase K, Taylor K, Suzuki K, Tadokoro K, Juji T (1998) Dendritic cells stimulate the expansion of bcr-abl specific CD8+ T cells with cytotoxic activity against leukemic cells from patients with chronic myeloid leukemia. Blood 91(3):977–983PubMed

20.

Norbury LC, Clark RE, Christmas SE (2000) b3a2 BCR-ABL fusion peptides as targets for cytotoxic T cells in chronic myeloid leukaemia. Br J Haematol 109(3):616–621PubMedCrossRef

21.

Osman Y, Takahashi M, Zheng Z, Koike T, Toba K, Liu A, Furukawa T, Aoki S, Aizawa Y (1999) Generation of bcr-abl specific cytotoxic T-lymphocytes by using dendritic cells pulsed with bcr-abl (b3a2) peptide: its applicability for donor leukocyte transfusions in marrow grafted CML patients. Leukemia 13(2):166–174PubMedCrossRef

22.

Pawelec G, Max H, Halder T, Bruserud O, Merl A, da Silva P, Kalbacher H (1996) BCR/ABL leukemia oncogene fusion peptides selectively bind to certain HLA-DR alleles and can be recognized by T cells found at low frequency in the repertoire of normal donors. Blood 88(6):2118–2124PubMed

23.

Pinilla-Ibarz J, Korontsvit T, Zakhaleva V, Roberts W, Scheinberg DA (2005) Synthetic peptide analogs derived from bcr/abl fusion proteins and the induction of heteroclitic human T-cell responses. Haematologica 90(10):1324–1332PubMed

24.

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(5):1781–1787PubMed

25.

Posthuma EF, van Bergen CA, Kester MG, de Paus RA, van Veelen PA, de Ru AH, Drijfhout JW, Lurvink EG, Willemze R, Falkenburg JH (2004) Proteosomal degradation of BCR/ABL protein can generate an HLA-A*0301-restricted peptide, but high-avidity T cells recognizing this leukemia-specific antigen were not demonstrated. Haematologica 89(9):1062–1071PubMed

26.

Posthuma EF, Falkenburg JH, Apperley JF, Gratwohl A, Roosnek E, Hertenstein B, Schipper RF, Schreuder GM, D’Amaro J, Oudshoorn M, van Biezen JH, Hermans J, Willemze R, Niederwieser D (1999) HLA-B8 and HLA-A3 coexpressed with HLA-B8 are associated with a reduced risk of the development of chronic myeloid leukemia. The Chronic Leukemia Working Party of the EBMT. Blood 93(11):3863–3865PubMed

27.

Rojas JM, Knight K, Wang L, Clark RE (2007) Clinical evaluation of BCR-ABL peptide immunisation in chronic myeloid leukaemia: results of the EPIC study. Leukemia 21(11):2287–2295PubMedCrossRef

28.

Rowley JD (1973) Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243(5405):290–293PubMedCrossRef

29.

ten Bosch GJ, Toornvliet AC, Friede T, Melief CJ, Leeksma OC (1995) Recognition of peptides corresponding to the joining region of p210BCR-ABL protein by human T cells. Leukemia 9(8):1344–1348PubMed

30.

Volpe G, Cignetti A, Panuzzo C, Kuka M, Vitaggio K, Brancaccio M, Perrone G, Rinaldi M, Prato G, Fava M, Geuna M, Pautasso M, Casnici C, Signori E, Tonon G, Tarone G, Marelli O, Fazio VM, Saglio G (2007) Alternative BCR/ABL splice variants in Philadelphia chromosome-positive leukemias result in novel tumor-specific fusion proteins that may represent potential targets for immunotherapy approaches. Cancer Res 67(11):5300–5307PubMedCrossRef

31.

Westermann J, Schlimper C, Richter G, Mohm J, Dorken B, Pezzutto A (2004) T cell recognition of bcr/abl in healthy donors and in patients with chronic myeloid leukaemia. Br J Haematol 125(2):213–216PubMedCrossRef

32.

Yasukawa M, Ohminami H, Kojima K, Hato T, Hasegawa A, Takahashi T, Hirai H, Fujita S (2001) HLA class II-restricted antigen presentation of endogenous bcr-abl fusion protein by chronic myelogenous leukemia-derived dendritic cells to CD4(+) T lymphocytes. Blood 98(5):1498–1505PubMedCrossRef

33.

Yasukawa M, Ohminami H, Kaneko S, Yakushijin Y, Nishimura Y, Inokuchi K, Miyakuni T, Nakao S, Kishi K, Kubonishi I, Dan K, Fujita S (1998) CD4(+) cytotoxic T-cell clones specific for bcr-abl b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner. Blood 92(9):3355–3361PubMed

34.

Yotnda P, Firat H, Garcia-Pons F, Garcia Z, Gourru G, Vernant JP, Lemonnier FA, Leblond V, Langlade-Demoyen P (1998) Cytotoxic T cell response against the chimeric p210 BCR-ABL protein in patients with chronic myelogenous leukemia. J Clin Invest 101(10):2290–2296PubMedCrossRef

Titel: BCR/ABL-specific CD8+ T cells can be detected from CML patients, but are only expanded from healthy donors
verfasst von: Sylvie Rusakiewicz
Alejandro Madrigal
Paul Travers
Anthony I. Dodi
Publikationsdatum: 01.09.2009
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 9/2009
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-009-0703-x

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

BCR/ABL-specific CD8⁺ T cells can be detected from CML patients, but are only expanded from healthy donors

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

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

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

Weitere Artikel der Ausgabe 9/2009

Expression of adhesion molecules and ligands for activating and costimulatory receptors involved in cell-mediated cytotoxicity in a large panel of human melanoma cell lines

HLA and melanoma: multiple alterations in HLA class I and II expression in human melanoma cell lines from ESTDAB cell bank

Soluble HLA/peptide monomers cross-linked with co-stimulatory antibodies onto a streptavidin core molecule efficiently stimulate antigen-specific T cell responses

−509C>T polymorphism in the TGF-β1 gene promoter, impact on the hepatocellular carcinoma risk in Chinese patients with chronic hepatitis B virus infection

Toll-like receptor expression in normal ovary and ovarian tumors

CD4+ T cell responses to HLA-DP5-restricted wild-type sequence p53 peptides in patients with head and neck cancer

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