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Tumor-specific idiotype vaccines in the treatment of patients with B- cell
lymphoma--long-term results of a clinical trial
FJ Hsu, CB Caspar, D Czerwinski, LW Kwak, TM Liles, A Syrengelas, B Taidi- Laskowski and R Levy
Division of Oncology, Stanford University Medical Center, CA 94305, USA.
The surface Ig on each B-cell lymphoma has unique portions (idiotypes),
which can be recognized by the immune system. In this study, we immunized
patients against the Ig expressed by their tumor and observed their
clinical outcomes. After standard chemotherapy, 41 patients with
non-Hodgkin's B-cell lymphoma received a series of injections with a
vaccine consisting of tumor Ig protein coupled to keyhole limpet hemocyanin
and emulsified in an immunologic adjuvant. Subjects were observed for
toxicity, immune responses, and tumor status. The median duration of
follow-up of all patients is 7.3 years from diagnosis and 5.3 years from
the last chemotherapy given before vaccine treatment. Twenty patients (49%)
generated specific immune responses against the idiotypes of their tumor
Ig. Two patients who had residual disease experienced complete tumor
regression in association with the development of these immune responses.
The median duration of freedom from disease progression and overall
survival of all 20 patients mounting an anti-idiotype immune response are
significantly prolonged compared to the patients who did not mount an
immune response. Thirty- two patients were in their first remission and
nine were in subsequent remissions before beginning vaccine treatments.
Analysis of the 32 first remission patients also shows an improved clinical
outcome for those patients who mounted a specific immune response compared
to those who did not (freedom from progression, 7.9 years v 1.3 years P =
.0001; median survival from time of last chemotherapy not yet reached v 7
years, P = .04). This study confirms an earlier report that patients with
B-cell lymphoma can be induced to make a specific immune response against
the Ig expressed by their own tumor. It further shows that the ability to
make such an immune response is correlated with a more favorable clinical
outcome. Prospective controlled trials will be needed to prove a causal
relationship between anti-idiotype immunity and improved clinical outcome.
Volume 89,
Issue 9,
pp. 3129-3135,
05/01/1997
Copyright © 1997 by The American Society of Hematology
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180(9):
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109(12):
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109(12):
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April 15, 2007;
109(8):
3393 - 3399.
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[Full Text]
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[Full Text]
[PDF]
|
|
|
|
|
|
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February 1, 2007;
18(2):
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[Full Text]
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|
|
|
|
|
|
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February 1, 2007;
109(3):
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[Abstract]
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|
|
|
|
|
|
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January 1, 2007;
178(1):
566 - 573.
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|
|
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January 1, 2007;
2007(1):
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|
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January 1, 2007;
2007(1):
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108(12):
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|
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|
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|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
|
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DNA vaccines to attack cancer
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October 5, 2004;
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14646 - 14652.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Lou, R. J. Kelleher Jr, A. Sette, J. Loyall, S. Southwood, R. B. Bankert, and S. H. Bernstein
Germ line tumor-associated immunoglobulin VH region peptides provoke a tumor-specific immune response without altering the response potential of normal B cells
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August 1, 2004;
104(3):
752 - 759.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bendandi, S. A. Pileri, and P. L. Zinzani
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Ann. Onc.,
May 1, 2004;
15(5):
703 - 711.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. G. Laport, B. L. Levine, E. A. Stadtmauer, S. J. Schuster, S. M. Luger, S. Grupp, N. Bunin, F. J. Strobl, J. Cotte, Z. Zheng, et al.
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September 15, 2003;
102(6):
2004 - 2013.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Winter, E. Fiebiger, P. Meraner, H. Auer, C. Brna, R. Strohal, F. Trautinger, R. Knobler, G. F. Fischer, G. Stingl, et al.
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J. Immunol.,
September 1, 2003;
171(5):
2714 - 2724.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Milazzo, V. L. Reichardt, M. R. Muller, F. Grunebach, and P. Brossart
Induction of myeloma-specific cytotoxic T cells using dendritic cells transfected with tumor-derived RNA
Blood,
February 1, 2003;
101(3):
977 - 982.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Xie, H.-H. Wacker, S. Huang, E. Regitz, K.-D. Preuss, B. Romeike, R. Parwaresch, M. Tiemann, and M. Pfreundschuh
Differential Expression of Cancer Testis Genes in Histological Subtypes of Non-Hodgkin's Lymphomas
Clin. Cancer Res.,
January 1, 2003;
9(1):
167 - 173.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Heslop, F. K. Stevenson, and J. J. Molldrem
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January 1, 2003;
2003(1):
331 - 349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Alain, K. Hirasawa, K. J. Pon, S. G. Nishikawa, S. J. Urbanski, Y. Auer, J. Luider, A. Martin, R. N. Johnston, A. Janowska-Wieczorek, et al.
Reovirus therapy of lymphoid malignancies
Blood,
December 1, 2002;
100(12):
4146 - 4153.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Gatza and C. Y. Okada
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J. Immunol.,
November 1, 2002;
169(9):
5227 - 5235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Timmerman, G. Singh, G. Hermanson, P. Hobart, D. K. Czerwinski, B. Taidi, R. Rajapaksa, C. B. Caspar, A. van Beckhoven, and R. Levy
Immunogenicity of a Plasmid DNA Vaccine Encoding Chimeric Idiotype in Patients with B-Cell Lymphoma
Cancer Res.,
October 15, 2002;
62(20):
5845 - 5852.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. E. van der Kolk, J. W. Baars, M. H. Prins, and M. H. J. van Oers
Rituximab treatment results in impaired secondary humoral immune responsiveness
Blood,
August 28, 2002;
100(6):
2257 - 2259.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hunault-Berger, N. Ifrah, and P. Solal-Celigny
Intensive therapies in follicular non-Hodgkin lymphomas
Blood,
July 30, 2002;
100(4):
1141 - 1152.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-J. Wen, R. Min, G. Tricot, B. Barlogie, and Q. Yi
Tumor lysate-specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy
Blood,
May 1, 2002;
99(9):
3280 - 3285.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. L. Berinstein
Carcinoembryonic Antigen as a Target for Therapeutic Anticancer Vaccines: A Review
J. Clin. Oncol.,
April 15, 2002;
20(8):
2197 - 2207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Thirdborough, J. N. Radcliffe, P. S. Friedmann, and F. K. Stevenson
Vaccination with DNA Encoding a Single-Chain TCR Fusion Protein Induces Anticlonotypic Immunity and Protects against T-Cell Lymphoma
Cancer Res.,
March 1, 2002;
62(6):
1757 - 1760.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Timmerman, D. K. Czerwinski, T. A. Davis, F. J. Hsu, C. Benike, Z. M. Hao, B. Taidi, R. Rajapaksa, C. B. Caspar, C. Y. Okada, et al.
Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients
Blood,
March 1, 2002;
99(5):
1517 - 1526.
[Abstract]
[Full Text]
[PDF]
|
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|
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