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Targeting of the WT191–138 fragment to human dendritic cells improves leukemia-specific T-cell responses providing an alternative approach to WT1-based vaccination

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Abstract

Due to its immunogenicity and overexpression concomitant with leukemia progression, Wilms tumor protein 1 (WT1) is of particular interest for immunotherapy of AML relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly been induced by vaccination with peptides presented by certain HLA alleles. However, this approach is still not widely applicable in clinical practice due to common limitations of HLA restriction. Dendritic cell (DC) vaccines electroporated with mRNA encoding full-length protein have also been tested for generating WT1-derived peptides for presentation to T-cells. Alternatively, an efficient and broad WT1 peptide presentation could be elicited by triggering receptor-mediated protein endocytosis of DCs. Therefore, we developed antibody fusion proteins consisting of an antibody specific for the DEC205 endocytic receptor on human DCs and various fragments of WT1 as DC-targeting recombinant WT1 vaccines (anti-hDEC205-WT1). Of all anti-hDEC205-WT1 fusion proteins designed for overcoming insufficient expression, anti-hDEC205-WT110–35, anti-hDEC205-WT191–138, anti-hDEC205-WT1223–273, and anti-hDEC205-WT1324–371 were identified in good yields. The anti-hDEC205-WT191–138 was capable of directly inducing ex vivo T-cell responses by co-incubation of the fusion protein-loaded monocyte-derived mature DCs and autologous T-cells of either healthy or HSCT individuals. Furthermore, the DC-targeted WT191–138-induced specific T-cells showed a strong cytotoxic activity by lysing WT1-overexpressing THP-1 leukemia cells in vitro while sparing WT1-negative hematopoietic cells. In conclusion, our approach identifies four WT1 peptide-antibody fusion proteins with sufficient production and introduces an alternative vaccine that could be easily translated into clinical practice to improve WT1-directed antileukemia immune responses after allo-HSCT.

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Abbreviations

aa:

Amino acid

AML:

Acute myeloid leukemia

CAR:

Chimeric antigen receptor

CHO:

Chinese hamster ovary

CHO-hDEC205:

hDEC205-stably expressing CHO

CMV:

Cytomegalovirus

CTL:

Cytotoxic T lymphocyte

ET:

Effector to target ratio

ELISPOT:

Enzyme-linked immuno spot

FCS:

Fetal calf serum

GM-CSF:

Granulocyte–macrophage colony stimulating factor

GpL:

Gaussia princeps luciferase

GvL:

Graft-versus-leukemia

hDEC205:

Human DEC205 endocytic receptor

HEK293:

Human embryonic kidney

HLA:

Human leukocyte antigen

HSCT:

Hematopoietic stem cell transplantation

IC50 :

50% inhibitory concentration

ICS:

Intracellular cytokine staining

IFN:

Interferon

IL:

Interleukin

K d :

Dissociation constant

K i :

Dissociation constant of inhibitor

LAL:

Limulus amebocyte lysate

MDS:

Myelodysplastic syndrome

moDCs:

Monocyte-derived dendritic cells

NBT/BCIP:

Nitro blue tetrazolium/5-Bromo-4-chloro-3-indolyl phosphate

PBMCs:

Peripheral blood mononuclear cells

PHA-L:

Phytohemagglutinin-L

pM:

Picomolar

PN:

Patient number

RT-PCR:

Reverse transcriptase polymerase chain reaction

scFv:

Single chain variable fragment

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

TAA:

Tumor-associated antigen

TCR:

T-cell receptor

TNF:

Tumor necrosis factor

WT1:

Wilms tumor protein

WT1_D:

Isoform D of WT1 protein

WT1full :

WT1 in full-length

WT1major and WT1small :

Major and small fragments of WT1 protein

References

  1. Savani BN, Mielke S, Reddy N, Goodman S, Jagasia M, Rezvani K (2009) Management of relapse after allo-SCT for AML and the role of second transplantation. Bone Marrow Transplant 44(12):769–777. doi:10.1038/bmt.2009.300

    Article  CAS  PubMed  Google Scholar 

  2. Lichtenegger FS, Krupka C, Kohnke T, Subklewe M (2015) Immunotherapy for acute myeloid leukemia. Semin Hematol 52(3):207–214. doi:10.1053/j.seminhematol.2015.03.006

    Article  CAS  PubMed  Google Scholar 

  3. Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, Mellman I, Prindiville SA, Viner JL, Weiner LM, Matrisian LM (2009) The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res 15(17):5323–5337. doi:10.1158/1078-0432.CCR-09-0737

    Article  PubMed  Google Scholar 

  4. Benteyn D, Anguille S, Van Lint S, Heirman C, Van Nuffel AM, Corthals J, Ochsenreither S, Waelput W, Van Beneden K, Breckpot K, Van Tendeloo V, Thielemans K, Bonehill A (2013) Design of an optimized Wilms’ tumor 1 (WT1) mRNA construct for enhanced WT1 expression and improved immunogenicity in vitro and in vivo. Mol Ther Nucleic Acids 2:e134. doi:10.1038/mtna.2013.54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kuball J, de Boer K, Wagner E, Wattad M, Antunes E, Weeratna RD, Vicari AP, Lotz C, van Dorp S, Hol S, Greenberg PD, Heit W, Davis HL, Theobald M (2011) Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909. Cancer Immunol Immunother 60(2):161–171. doi:10.1007/s00262-010-0929-7

    Article  CAS  PubMed  Google Scholar 

  6. Chaise C, Buchan SL, Rice J, Marquet J, Rouard H, Kuentz M, Vittes GE, Molinier-Frenkel V, Farcet JP, Stauss HJ, Delfau-Larue MH, Stevenson FK (2008) DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance. Blood 112(7):2956–2964. doi:10.1182/blood-2008-02-137695

    Article  CAS  PubMed  Google Scholar 

  7. Van Driessche A, Van de Velde AL, Nijs G, Braeckman T, Stein B, De Vries JM, Berneman ZN, Van Tendeloo VF (2009) Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial. Cytotherapy 11(5):653–668. doi:10.1080/14653240902960411

    Article  PubMed  Google Scholar 

  8. Maslak PG, Dao T, Krug LM, Chanel S, Korontsvit T, Zakhaleva V, Zhang R, Wolchok JD, Yuan J, Pinilla-Ibarz J, Berman E, Weiss M, Jurcic J, Frattini MG, Scheinberg DA (2010) Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia. Blood 116(2):171–179. doi:10.1182/blood-2009-10-250993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Weber G, Gerdemann U, Caruana I, Savoldo B, Hensel NF, Rabin KR, Shpall EJ, Melenhorst JJ, Leen AM, Barrett AJ, Bollard CM (2013) Generation of multi-leukemia antigen-specific T cells to enhance the graft-versus-leukemia effect after allogeneic stem cell transplant. Leukemia 27(7):1538–1547. doi:10.1038/leu.2013.66

    Article  CAS  PubMed  Google Scholar 

  10. Brayer J, Lancet JE, Powers J, List A, Balducci L, Komrokji R, Pinilla-Ibarz J (2015) WT1 vaccination in AML and MDS: a pilot trial with synthetic analog peptides. Am J Hematol 90(7):602–607. doi:10.1002/ajh.24014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kramarzova K, Stuchly J, Willasch A, Gruhn B, Schwarz J, Cermak J, Machova-Polakova K, Fuchs O, Stary J, Trka J, Boublikova L (2012) Real-time PCR quantification of major Wilms’ tumor gene 1 (WT1) isoforms in acute myeloid leukemia, their characteristic expression patterns and possible functional consequences. Leukemia 26(9):2086–2095. doi:10.1038/leu.2012.76

    Article  CAS  PubMed  Google Scholar 

  12. Niksic M, Slight J, Sanford JR, Caceres JF, Hastie ND (2004) The Wilms’ tumour protein (WT1) shuttles between nucleus and cytoplasm and is present in functional polysomes. Hum Mol Genet 13(4):463–471. doi:10.1093/hmg/ddh040

    Article  CAS  PubMed  Google Scholar 

  13. Hamilton TB, Barilla KC, Romaniuk PJ (1995) High affinity binding sites for the Wilms’ tumour suppressor protein WT1. Nucleic Acids Res 23(2):277–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ladomery MR, Slight J, Mc Ghee S, Hastie ND (1999) Presence of WT1, the Wilm’s tumor suppressor gene product, in nuclear poly(A)(+) ribonucleoprotein. J Biol Chem 274(51):36520–36526

    Article  CAS  PubMed  Google Scholar 

  15. Geng J, Carstens RP (2006) Two methods for improved purification of full-length mammalian proteins that have poor expression and/or solubility using standard Escherichia coli procedures. Protein Expr Purif 48(1):142–150. doi:10.1016/j.pep.2006.01.021

    Article  CAS  PubMed  Google Scholar 

  16. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392(6673):245–252. doi:10.1038/32588

    Article  CAS  PubMed  Google Scholar 

  17. Steinman RM, Banchereau J (2007) Taking dendritic cells into medicine. Nature 449(7161):419–426. doi:10.1038/nature06175

    Article  CAS  PubMed  Google Scholar 

  18. Romao S, Gannage M, Munz C (2013) Checking the garbage bin for problems in the house, or how autophagy assists in antigen presentation to the immune system. Semin Cancer Biol 23(5):391–396. doi:10.1016/j.semcancer.2013.03.001

    Article  CAS  PubMed  Google Scholar 

  19. Talarn C, Urbano-Ispizua A, Martino R, Perez-Simon JA, Batlle M, Herrera C, Granell M, Gaya A, Torrebadell M, Fernandez-Aviles F, Aymerich M, Marin P, Sierra J, Montserrat E (2007) Kinetics of recovery of dendritic cell subsets after reduced-intensity conditioning allogeneic stem cell transplantation and clinical outcome. Haematologica 92(12):1655–1663. doi:10.3324/haematol.11076

    Article  PubMed  Google Scholar 

  20. Birkholz K, Schwenkert M, Kellner C, Gross S, Fey G, Schuler-Thurner B, Schuler G, Schaft N, Dorrie J (2010) Targeting of DEC-205 on human dendritic cells results in efficient MHC class II-restricted antigen presentation. Blood 116(13):2277–2285. doi:10.1182/blood-2010-02-268425

    Article  CAS  PubMed  Google Scholar 

  21. Tsuji T, Matsuzaki J, Kelly MP, Ramakrishna V, Vitale L, He LZ, Keler T, Odunsi K, Old LJ, Ritter G, Gnjatic S (2011) Antibody-targeted NY-ESO-1 to mannose receptor or DEC-205 in vitro elicits dual human CD8+ and CD4+ T cell responses with broad antigen specificity. J Immunol 186(2):1218–1227. doi:10.4049/jimmunol.1000808

    Article  CAS  PubMed  Google Scholar 

  22. Wang B, Zaidi N, He LZ, Zhang L, Kuroiwa JM, Keler T, Steinman RM (2012) Targeting of the non-mutated tumor antigen HER2/neu to mature dendritic cells induces an integrated immune response that protects against breast cancer in mice. Breast Cancer Res BCR 14(2):R39. doi:10.1186/bcr3135

    Article  CAS  PubMed  Google Scholar 

  23. Tan SM, Kapp M, Flechsig C, Kapp K, Rachor JE, Eyrich M, Loeffler J, Einsele H, Grigoleit GU (2013) Stimulating surface molecules, Th1-polarizing cytokines, proven trafficking—a new protocol for the generation of clinical-grade dendritic cells. Cytotherapy 15(4):492–506. doi:10.1016/j.jcyt.2012.12.002

    Article  CAS  PubMed  Google Scholar 

  24. Lamoreaux L, Roederer M, Koup R (2006) Intracellular cytokine optimization and standard operating procedure. Nat Protoc 1(3):1507–1516. doi:10.1038/nprot.2006.268

    Article  CAS  PubMed  Google Scholar 

  25. Stanke J, Hoffmann C, Erben U, von Keyserling H, Stevanovic S, Cichon G, Schneider A, Kaufmann AM (2010) A flow cytometry-based assay to assess minute frequencies of CD8+ T cells by their cytolytic function. J Immunol Methods 360(1–2):56–65. doi:10.1016/j.jim.2010.06.005

    Article  CAS  PubMed  Google Scholar 

  26. Rezvani K (2011) Posttransplantation vaccination: concepts today and on the horizon. Hematology Am Soc Hematol Educ Program 2011:299–304. doi:10.1182/asheducation-2011.1.299

    PubMed  Google Scholar 

  27. Nurmemmedov E, Thunnissen M (2006) Expression, purification, and characterization of the 4 zinc finger region of human tumor suppressor WT1. Protein Expr Purif 46(2):379–389. doi:10.1016/j.pep.2005.10.029

    Article  CAS  PubMed  Google Scholar 

  28. Fagerlund RD, Ooi PL, Wilbanks SM (2012) Soluble expression and purification of tumor suppressor WT1 and its zinc finger domain. Protein Expr Purif 85(2):165–172. doi:10.1016/j.pep.2012.08.002

    Article  CAS  PubMed  Google Scholar 

  29. Doubrovina E, Carpenter T, Pankov D, Selvakumar A, Hasan A, O’Reilly RJ (2012) Mapping of novel peptides of WT-1 and presenting HLA alleles that induce epitope-specific HLA-restricted T cells with cytotoxic activity against WT-1(+) leukemias. Blood 120(8):1633–1646. doi:10.1182/blood-2011-11-394619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kobayashi H, Nagato T, Aoki N, Sato K, Kimura S, Tateno M, Celis E (2006) Defining MHC class II T helper epitopes for WT1 tumor antigen. Cancer Immunol Immunother 55(7):850–860. doi:10.1007/s00262-005-0071-0

    Article  CAS  PubMed  Google Scholar 

  31. Oka Y, Elisseeva OA, Tsuboi A, Ogawa H, Tamaki H, Li H, Oji Y, Kim EH, Soma T, Asada M, Ueda K, Maruya E, Saji H, Kishimoto T, Udaka K, Sugiyama H (2000) Human cytotoxic T-lymphocyte responses specific for peptides of the wild-type Wilms’ tumor gene (WT1) product. Immunogenetics 51(2):99–107

    Article  CAS  PubMed  Google Scholar 

  32. Rezvani K, Yong AS, Mielke S, Savani BN, Musse L, Superata J, Jafarpour B, Boss C, Barrett AJ (2008) Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood 111(1):236–242. doi:10.1182/blood-2007-08-108241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, Brimnes MK, Moltedo B, Moran TM, Steinman RM (2004) In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med 199(6):815–824. doi:10.1084/jem.20032220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cheong C, Choi JH, Vitale L, He LZ, Trumpfheller C, Bozzacco L, Do Y, Nchinda G, Park SH, Dandamudi DB, Shrestha E, Pack M, Lee HW, Keler T, Steinman RM, Park CG (2010) Improved cellular and humoral immune responses in vivo following targeting of HIV Gag to dendritic cells within human anti-human DEC205 monoclonal antibody. Blood 116(19):3828–3838. doi:10.1182/blood-2010-06-288068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Koido S, Homma S, Okamoto M, Takakura K, Gong J, Sugiyama H, Ohkusa T, Tajiri H (2014) Chemoimmunotherapy targeting Wilms’ tumor 1 (WT1)-specific cytotoxic T lymphocyte and helper T cell responses for patients with pancreatic cancer. Oncoimmunology 3(10):e958950. doi:10.4161/21624011.2014.958950

    Article  PubMed  PubMed Central  Google Scholar 

  36. Fujiki F, Oka Y, Tsuboi A, Kawakami M, Kawakatsu M, Nakajima H, Elisseeva OA, Harada Y, Ito K, Li Z, Tatsumi N, Sakaguchi N, Fujioka T, Masuda T, Yasukawa M, Udaka K, Kawase I, Oji Y, Sugiyama H (2007) Identification and characterization of a WT1 (Wilms Tumor Gene) protein-derived HLA-DRB1*0405-restricted 16-mer helper peptide that promotes the induction and activation of WT1-specific cytotoxic T lymphocytes. J Immunother 30(3):282–293. doi:10.1097/01.cji.0000211337.91513.94

    Article  CAS  PubMed  Google Scholar 

  37. Sehgal K, Dhodapkar KM, Dhodapkar MV (2014) Targeting human dendritic cells in situ to improve vaccines. Immunol Lett 162(1 Pt A):59–67. doi:10.1016/j.imlet.2014.07.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Grigoleit GU, Kapp M, Hebart H, Fick K, Beck R, Jahn G, Einsele H (2007) Dendritic cell vaccination in allogeneic stem cell recipients: induction of human cytomegalovirus (HCMV)-specific cytotoxic T lymphocyte responses even in patients receiving a transplant from an HCMV-seronegative donor. J Infect Dis 196(5):699–704. doi:10.1086/520538

    Article  PubMed  Google Scholar 

  39. Chapuis AG, Ragnarsson GB, Nguyen HN, Chaney CN, Pufnock JS, Schmitt TM, Duerkopp N, Roberts IM, Pogosov GL, Ho WY, Ochsenreither S, Wolfl M, Bar M, Radich JP, Yee C, Greenberg PD (2013) Transferred WT1-reactive CD8+ T cells can mediate antileukemic activity and persist in post-transplant patients. Sci Transl Med 5(174):174ra127. doi:10.1126/scitranslmed.3004916

    Article  Google Scholar 

  40. Plantinga M, de Haar C, Nierkens S, Boelens JJ (2014) Dendritic cell therapy in an allogeneic-hematopoietic cell transplantation setting: an effective strategy toward better disease control? Front Immunol 5:218. doi:10.3389/fimmu.2014.00218

    Article  PubMed  PubMed Central  Google Scholar 

  41. Sundarasetty BS, Kloess S, Oberschmidt O, Naundorf S, Kuehlcke K, Daenthanasanmak A, Gerasch L, Figueiredo C, Blasczyk R, Ruggiero E, Fronza R, Schmidt M, von Kalle C, Rothe M, Ganser A, Koehl U, Stripecke R (2015) Generation of lentivirus-induced dendritic cells under GMP-compliant conditions for adaptive immune reconstitution against cytomegalovirus after stem cell transplantation. J Transl Med 13:240. doi:10.1186/s12967-015-0599-5

    Article  PubMed  PubMed Central  Google Scholar 

  42. Di Stasi A, Jimenez AM, Minagawa K, Al-Obaidi M, Rezvani K (2015) Review of the results of WT1 peptide vaccination strategies for myelodysplastic syndromes and acute myeloid leukemia from nine different studies. Front Immunol 6:36. doi:10.3389/fimmu.2015.00036

    Article  PubMed  PubMed Central  Google Scholar 

  43. Woehlecke C, Wittig S, Arndt C, Gruhn B (2015) Prognostic impact of WT1 expression prior to hematopoietic stem cell transplantation in children with malignant hematological diseases. J Cancer Res Clin Oncol 141(3):523–529. doi:10.1007/s00432-014-1832-y

    Article  CAS  PubMed  Google Scholar 

  44. Yi-Ning Y, Xiao-rui W, Chu-xian Z, Chun W, You-wen Q (2015) Prognostic significance of diagnosed WT1 level in acute myeloid leukemia: a meta-analysis. Ann Hematol 94(6):929–938. doi:10.1007/s00277-014-2295-6

    Article  PubMed  Google Scholar 

  45. Casalegno-Garduño R, Schmitt A, Spitschak A, Greiner J, Wang L, Hilgendorf I, Hirt C, Ho AD, Freund M, Schmitt M (2016) Immune responses to WT1 in patients with AML or MDS after chemotherapy and allogeneic stem cell transplantation. Int J Cancer 138(7):1792–1801. doi:10.1002/ijc.29909

    Article  PubMed  Google Scholar 

  46. Qi XW, Zhang F, Wu H, Liu JL, Zong BG, Xu C, Jiang J (2015) Wilms’ tumor 1 (WT1) expression and prognosis in solid cancer patients: a systematic review and meta-analysis. Sci Rep 5:8924. doi:10.1038/srep08924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Oka Y, Tsuboi A, Taguchi T, Osaki T, Kyo T, Nakajima H, Elisseeva OA, Oji Y, Kawakami M, Ikegame K, Hosen N, Yoshihara S, Wu F, Fujiki F, Murakami M, Masuda T, Nishida S, Shirakata T, Nakatsuka S, Sasaki A, Udaka K, Dohy H, Aozasa K, Noguchi S, Kawase I, Sugiyama H (2004) Induction of WT1 (Wilms’ tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression. Proc Natl Acad Sci USA 101(38):13885–13890. doi:10.1073/pnas.0405884101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Keilholz U, Letsch A, Busse A, Asemissen AM, Bauer S, Blau IW, Hofmann WK, Uharek L, Thiel E, Scheibenbogen C (2009) A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood 113(26):6541–6548. doi:10.1182/blood-2009-02-202598

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank our colleagues in the Division of Molecular Internal Medicine for their assistance and Professor Matthias Eyrich for his critical discussion. We also thank Dr. Torsten Steinbrunn for proofreading of the manuscript. Nergui Dagvadorj was supported by scholarships from the Government of Mongolia, the Fritz Thyssen Foundation of Germany, the Interdisciplinary Center for Clinical Research (IZKF) of the University of Würzburg, Germany and the German Academic Exchange Service (DAAD), Germany.

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Authors and Affiliations

  1. Laboratory for Immunotherapy, Department of Internal Medicine II, University Hospital of Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany

    Nergui Dagvadorj, Anne Deuretzbacher, Elke Baumeister, Carolin Köchel, Markus Kapp, Kerstin Kapp, Hermann Einsele & Götz Ulrich Grigoleit

  2. Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany

    Daniela Weisenberger, Johannes Trebing, Isabell Lang & Harald Wajant

  3. Division of Experimental Stem Cell Transplantation, Interdisciplinary Center for Clinical Research, University of Würzburg, Würzburg, Germany

    Andreas Beilhack

  4. Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany

    Thomas Hünig

  5. Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia

    Nergui Dagvadorj

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  1. Nergui Dagvadorj
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  2. Anne Deuretzbacher
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Dagvadorj, N., Deuretzbacher, A., Weisenberger, D. et al. Targeting of the WT191–138 fragment to human dendritic cells improves leukemia-specific T-cell responses providing an alternative approach to WT1-based vaccination. Cancer Immunol Immunother 66, 319–332 (2017). https://doi.org/10.1007/s00262-016-1938-y

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