CoChat
Sign Up
Cited by 36Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyRNA Interference and Gene Delivery

Ex vivo induction of viral antigen-specific CD8+ T cell responses using mRNA-electroporated CD40-activated B cells

Open access
Van den Bosch, G A, Ponsaerts, P, Nijs, G, Lenjou, M, Vanham, G, Van Bockstaele, D R, Berneman, Z N, Van Tendeloo, V F I·2005·Clinical and Experimental Immunology
DOI 10.1111/j.1365-2249.2005.02733.xPMC PMC1809302
Open this paper in CoChat — free account

Abstract

Summary: Cell-based immunotherapy, in which antigen-loaded antigen-presenting cells (APC) are used to elicit T cell responses, has become part of the search for alternative cancer and infectious disease treatments. Here, we report on the feasibility of using mRNA-electroporated CD40-activated B cells (CD40-B cells) as alternative APC for the ex vivo induction of antigen-specific CD8+ T cell responses. The potential of CD40-B cells as APC is reflected in their phenotypic analysis, showing a polyclonal, strongly activated B cell population with high expression of MHC and co-stimulatory molecules. Flow cytometric analysis of EGFP expression 24 h after EGFP mRNA-electroporation showed that CD40-B cells can be RNA transfected with high gene transfer efficiency. No difference in transfection efficiency or postelectroporation viability was observed between CD40-B cells and monocyte-derived dendritic cells (DC). Our first series of experiments show clearly that peptide-pulsed CD40-B cells are able to (re)activate both CD8+ and CD4+ T cells against influenza and cytomegalovirus (CMV) antigens. To demonstrate the ability of viral antigen mRNA-electroporated CD40-B cells to induce virus-specific CD8+ T cell responses, these antigen-loaded cells were co-cultured in vitro with autologous peripheral blood mononuclear cells (PBMC) for 7 days followed by analysis of T cell antigen-specificity. These experiments show that CD40-B cells electroporated with influenza M1 mRNA or with CMV pp65 mRNA are able to activate antigen-specific interferon (IFN)-gamma-producing CD8+ T cells. These findings demonstrate that mRNA-electroporated CD40-B cells can be used as alternative APC for the induction of antigen-specific (memory) CD8+ T cell responses, which might overcome some of the drawbacks inherent to DC immunotherapy protocols.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/j.1365-2249.2005.02733.x

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 32

  1. [1]Nair SK, Boczkowski D, Morse M, Cumming RI, Lyerly HK, Gilboa E. Induction of primary carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes in vitro using human dendritic cells transfected with RNA. Nat Biotechnol. 1998;16:364–9. doi: 10.1038/nbt0498-364. [DOI] [PubMed] [Google Scholar] · DOI
  2. [2]Zhou Y, Bosch ML, Salgaller ML. Current methods for loading dendritic cells with tumor antigen for induction of antitumor immunity. J Immunother. 2002;25:289–303. doi: 10.1097/00002371-200207000-00001. [DOI] [PubMed] [Google Scholar] · DOI
  3. [3]Rubio V, Stuge TB, Singh N, et al. Ex vivo identification, isolation and analysis of tumor-cytolytic T cells. Nat Med. 2003;9:1377–82. doi: 10.1038/nm942. [DOI] [PubMed] [Google Scholar] · DOI
  4. [4]Thurner B, Haendle I, Röder C, et al. 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. 1999;11:1669–78. doi: 10.1084/jem.190.11.1669. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  5. [5]Rini BI. Technology evaluation. APC-8015, Dendreon. Curr Opin Mol Ther. 2002;4:76–9. [PubMed] [Google Scholar]
  6. [6]Heiser A, Coleman D, Dannull J, et al. Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors. J Clin Invest. 2002;109:409–17. doi: 10.1172/JCI14364. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  7. [7]Hsu FJ, Benike C, Fagnoni F, et al. Vaccination of patients with B-cell lymphoma with peptide-or tumor lysate-pulsed dendritic cells. Nat Med. 1998;4:328–32. doi: 10.1038/nm0398-328. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  8. [8]Maier T, Tun-Kyi A, Tassis A, et al. Vaccination of cutaneous T cell lymphoma patients using intranodal injection of autologous tumor lysate pulsed dendritic cells. Blood. 2003;102:2338–44. doi: 10.1182/blood-2002-08-2455. [DOI] [PubMed] [Google Scholar] · DOI
  9. [9]Kugler A, Stuhler G, Walden P, et al. Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat Med. 2000;6:332–6. doi: 10.1038/73193. [DOI] [PubMed] [Google Scholar] · DOI
  10. [10]Banchereau J, Palucka AK, Dhodapkar M, et al. Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res. 2001;61:6451–8. [PubMed] [Google Scholar]
  11. [11]Steinman RM, Witmer-Pack MD, Inaba K. Dendritic cells: antigen presentation, accessory function and clinical relevance. Adv Exp Med Biol. 1993;329:1–9. doi: 10.1007/978-1-4615-2930-9_1. [DOI] [PubMed] [Google Scholar] · DOI
  12. [12]Girolomoni G, Ricciardi Castagnoli P. Dendritic cells hold promise for immunotherapy. Immunol Today. 1997;18:102–4. doi: 10.1016/s0167-5699(97)01030-x. [DOI] [PubMed] [Google Scholar] · DOI
  13. [13]Banchereau J, Steiman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–52. doi: 10.1038/32588. [DOI] [PubMed] [Google Scholar] · DOI
  14. [14]Cerundolo V, Hermans IF, Salio M. Dendritic cells: a journey from laboratory to clinic. Nature Immunol. 2004;5:7–10. doi: 10.1038/ni0104-7. [DOI] [PubMed] [Google Scholar] · DOI
  15. [15]Schultze JL, Michalak S, Seamon MJ, et al. CD40-activated human B cells: an alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy. J Clin Invest. 1997;100:2757–65. doi: 10.1172/JCI119822. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  16. [16]Von Bergwel T, Baildon MS, Vonderheide RH, et al. Human primary and memory cytotoxic T lymphocyte responses are efficiently induced by means of CD40-activated B cells as antigen-presenting cells: potential for clinical application. Blood. 2002;99:3319–25. doi: 10.1182/blood.v99.9.3319. [DOI] [PubMed] [Google Scholar] · DOI
  17. [17]Kondo E, Topp MS, Kiem HP, et al. Efficient generation of antigen-specific cytotoxic T cells using retrovirally transduced CD40-activated B cells. J Immunol. 2002;169:2164–71. doi: 10.4049/jimmunol.169.4.2164. [DOI] [PubMed] [Google Scholar] · DOI
  18. [18]Lapointe R, Bellemare-Pelletier A, Housseau F, Thibodeau J, Hwu J. CD40-stimulated B lymphocytes pulsed with tumour antigens are effective antigen-presenting cells that can generate specific T cells. Cancer Res. 2003;63:2836–43. [PubMed] [Google Scholar]
  19. [19]Van Tendeloo VF, Ponsaerts P, Lardon F, et al. Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumour antigen loading of dendritic cells. Blood. 2001;98:49–56. doi: 10.1182/blood.v98.1.49. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  20. [20]Miller G, Lipman M. Release of infectious Epstein–Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci USA. 1973;70:190–4. doi: 10.1073/pnas.70.1.190. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  21. [21]Romani N, Reider D, Heuer M, et al. Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Meth. 1996;196:137–51. doi: 10.1016/0022-1759(96)00078-6. [DOI] [PubMed] [Google Scholar] · DOI
  22. [22]Boczkowski D, Nair SK, Snyder D, Gilboa E. Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med. 1996;184:465–72. doi: 10.1084/jem.184.2.465. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  23. [23]Strobel I, Berchtold S, Gotze A, Schulze U, Schuler G, Steinkasserer A. Human dendritic cells transfected with either RNA or DNA encoding influenza matrix protein M1 differ in their ability to stimulate cytotoxic T lymphocytes. Gene Ther. 2000;7:2028–35. doi: 10.1038/sj.gt.3301326. [DOI] [PubMed] [Google Scholar] · DOI
  24. [24]Ponsaerts P, Van Tendeloo VF, Cools N, et al. mRNA-electroporated mature dendritic cells retain transgene expression, phenotypical properties and stimulatory capacity after cryopreservation. Leukemia. 2002;16:1324–30. doi: 10.1038/sj.leu.2402511. [DOI] [PubMed] [Google Scholar] · DOI
  25. [25]Harris NL. Mature B-cell neoplasms. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. WHO classification of tumours − pathology, genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001. pp. 119–85. [Google Scholar]
  26. [26]Salkowitz JR, Sieg SF, Harding CV, Lederman MM. In vitro human memory CD8 T cell expansion in response to cytomegalovirus requires CD4+ T cell help. J Infect Dis. 2004;189:971–83. doi: 10.1086/382032. [DOI] [PubMed] [Google Scholar] · DOI
  27. [27]Riberdy JM, Christensen JP, Branum K, Doherty PC. Diminished primary and secondary influenza virus-specific CD8(+) T cell responses in CD4-depleted Ig(−/−) mice. J Virol. 2000;74:9762–5. doi: 10.1128/jvi.74.20.9762-9765.2000. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  28. [28]Coughlin CM, Vance BA, Grupp SA, Vonderheide RH. RNA-transfected CD40-activated B cells induce functional T cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy. Blood. 2004;103:2046–54. doi: 10.1182/blood-2003-07-2379. [DOI] [PubMed] [Google Scholar] · DOI
  29. [29]Lacey SF, Villacres MC, La Rosa C, et al. Relative dominance of HLA-B*07 restricted CD8+ T lymphocyte immune responses to human cytomegalovirus pp65 in persons sharing HLA-A*02 and HLA-B*07 alleles. Hum Immunol. 2003;64:440–52. doi: 10.1016/s0198-8859(03)00028-4. [DOI] [PubMed] [Google Scholar] · DOI
  30. [30]Bonehill A, Heirman C, Tuyaerts S, et al. Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in HLA class I and class II molecules. J Immunol. 2004;172:6649–57. doi: 10.4049/jimmunol.172.11.6649. [DOI] [PubMed] [Google Scholar] · DOI
  31. [31]Ponsaerts P, Van Tendeloo V, Berneman ZN. Cancer immunotherapy using RNA-loaded dendritic cells. Clin Exp Immunol. 2003;134:378–84. doi: 10.1046/j.1365-2249.2003.02286.x. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  32. [32]Roy MP, Kim CH, Butcher EC. Cytokine control of memory B cell homing machinery. J Immunol. 2002;169:1676–82. doi: 10.4049/jimmunol.169.4.1676. [DOI] [PubMed] [Google Scholar] · DOI

Cited by

Sorted by citations

Authors
Van den Bosch, G. A., Ponsaerts, P., Nijs, G., Lenjou, M., Vanham, G., Van Bockstaele, D. R., Berneman, Z. N., & Van Tendeloo, V. F. I.
Affiliations
  • Laboratory of Experimental Hematology, Antwerp University Hospital (UZA), University of Antwerp (UA), Belgium
  • University of Antwerp (BE)
  • Instituut voor Tropische Geneeskunde (BE)
ORCID
Venue
Clinical and Experimental Immunology
Publisher
Oxford University Press (OUP)
Published
2005-01-26
Volume
139
Issue
3
Pages
458-467
ISSN
  • 0009-9104 (ISSN-L)
  • 1365-2249
DOI
10.1111/j.1365-2249.2005.02733.x
PMC
PMC1809302
OpenAlex
W2094562987
Cited by
36
References
0
Citations by year
2026: 1 · 2023: 1 · 2022: 4 · 2021: 2 · 2019: 1 · 2018: 1 · 2015: 2 · 2014: 1 · 2013: 2
FWCI
1.89
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Clinical & Experimental Immunology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ludwig Institute for Cancer Research
  • Vlaamse regering
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
mRNA electroporation, antigen-presenting cells, CD8+ T cell responses, dendritic cell immunotherapy, T cell activation, interferon-gamma, cellular immunotherapy, memory T cells
MeSH terms
Antigen-Presenting Cells, Antigens, Viral, B-Lymphocytes, Cell Line, Cytomegalovirus, Histocompatibility Testing, Humans, Lymphocyte Activation, RNA, Messenger, Immunotherapy, Adoptive, Electroporation, CD8-Positive T-Lymphocytes, Cell Culture Techniques, CD40 Antigens, Green Fluorescent Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review