|
|
Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-04-1273.
Previous Article | Table of Contents | Next Article 
Blood, 1 February 2003, Vol. 101, No. 3, pp. 977-982
IMMUNOBIOLOGY
Induction of myeloma-specific cytotoxic T cells using dendritic
cells transfected with tumor-derived RNA
Caterina Milazzo,
Volker L. Reichardt,
Martin R. Müller,
Frank Grünebach, and
Peter Brossart
From the Department of Hematology, Oncology,
Immunology, and Rheumatology, University of Tübingen,
Germany.
Current immunotherapeutic trials for patients with multiple myeloma
(MM) focus on the idiotype (Id) as a tumor-specific antigen for
active immunization. To bypass the need for the identification of
shared MM-associated antigens and the characterization of possible immunogenic T-cell epitopes in a human leukocyte antigen (HLA) type-restricted manner, we focused on myeloma RNA transfection of dendritic cells (DCs). Total RNA encodes the whole antigen content
of tumor cells, therefore allowing the transfected DCs to process and
present the most relevant peptides and to induce a possible polyclonal
cytotoxic T lymphocyte (CTL) response against different
immunogenic antigens. We transfected monocyte-derived DCs with total
RNA from the myeloma cell lines LP-1 and U266 by electroporation
and investigated the potential of these DCs to induce myeloma-specific
CTLs. We show that RNA-transfected DCs induce CTLs that lyse the LP-1
and U266 myeloma cells in an antigen-specific and major
histocompatibility complex (MHC) class
I-restricted manner, as demonstrated by cold-target inhibition
and antibody-blocking studies. Interestingly, LP-1-specific CTLs
showed no specificity for the idiotype. Consistent with studies
demonstrating mucin 1 (MUC1) as a myeloma-associated antigen,
we found MUC1 specificity of the CTLs induced with U266-derived RNA. As
corresponding epitopes, we tested the described peptides M1.1 and M1.2
and found a striking fine specificity for M1.2, assuming a possible
immunodominance of this peptide. This is the first report on the
induction of myeloma-specific CTLs by RNA transfection of DCs.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
M. Martin-Ayuso, J. Almeida, M. Perez-Andres, R. Cuello, J. Galende, M. I. Gonzalez-Fraile, G. Martin-Nunez, F. Ortega, M. J. Rodriguez, J. F. San Miguel, et al.
Peripheral Blood Dendritic Cell Subsets from Patients with Monoclonal Gammopathies Show an Abnormal Distribution and Are Functionally Impaired
Oncologist,
January 1, 2008;
13(1):
82 - 92.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. N. Boss, F. Grunebach, K. Brauer, M. Hantschel, V. Mirakaj, T. Weinschenk, S. Stevanovic, H.-G. Rammensee, and P. Brossart
Identification and Characterization of T-Cell Epitopes Deduced from RGS5, a Novel Broadly Expressed Tumor Antigen
Clin. Cancer Res.,
June 1, 2007;
13(11):
3347 - 3355.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Grunebach, V. Mirakaj, V. Mirakaj, M. R. Muller, T. Brummendorf, and P. Brossart
BCR-ABL Is Not an Immunodominant Antigen in Chronic Myelogenous Leukemia
Cancer Res.,
June 1, 2006;
66(11):
5892 - 5900.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Geffroy-Luseau, A. Moreau-Aubry, R. Bataille, and C. Pellat-Deceunynck
Allogeneic T lymphocytes as a source of peptide-dependent T cells specific for myeloma cells
Int. Immunol.,
September 1, 2005;
17(9):
1193 - 1200.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Lotz, S. A. Mutallib, N. Oehlrich, U. Liewer, E. A. Ferreira, M. Moos, M. Hundemer, S. Schneider, S. Strand, C. Huber, et al.
Targeting Positive Regulatory Domain I-Binding Factor 1 and X Box-Binding Protein 1 Transcription Factors by Multiple Myeloma-Reactive CTL
J. Immunol.,
July 15, 2005;
175(2):
1301 - 1309.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. B. Rew, K. Peggs, I. Sanjuan, A. R. Pizzey, Y. Koishihara, S. Kawai, M. Kosaka, S. Ozaki, B. Chain, and K. L. Yong
Generation of Potent Antitumor CTL from Patients with Multiple Myeloma Directed against HM1.24
Clin. Cancer Res.,
May 1, 2005;
11(9):
3377 - 3384.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Dorfel, S. Appel, F. Grunebach, M. M. Weck, M. R. Muller, A. Heine, and P. Brossart
Processing and presentation of HLA class I and II epitopes by dendritic cells after transfection with in vitro-transcribed MUC1 RNA
Blood,
April 15, 2005;
105(8):
3199 - 3205.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. M. Coughlin, B. A. Vance, S. A. Grupp, and R. H. Vonderheide
RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy
Blood,
March 15, 2004;
103(6):
2046 - 2054.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|