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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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Antibodies Elicited by Naked DNA Vaccination against the Complementary-determining Region 3 Hypervariable Region of Immunoglobulin Heavy Chain Idiotypic Determinants of B-lymphoproliferative Disorders Specifically React with Patients' Tumor Cells
Cancer Res.,
February 1, 2001;
61(4):
1555 - 1562.
[Abstract]
[Full Text]
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O. W. Press, J. P. Leonard, B. Coiffier, R. Levy, and J. Timmerman
Immunotherapy of Non-Hodgkin's Lymphomas
Hematology,
January 1, 2001;
2001(1):
221 - 240.
[Abstract]
[Full Text]
[PDF]
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G. J. Weiner
The immunobiology and clinical potential of immunostimulatory CpG oligodeoxynucleotides
J. Leukoc. Biol.,
October 1, 2000;
68(4):
455 - 463.
[Abstract]
[Full Text]
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K. Pulford, B. Falini, A. H. Banham, D. Codrington, H. Roberton, C. Hatton, and D. Y. Mason
Immune response to the ALK oncogenic tyrosine kinase in patients with anaplastic large-cell lymphoma
Blood,
August 15, 2000;
96(4):
1605 - 1607.
[Abstract]
[Full Text]
[PDF]
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B. D. Cheson
The Curious Case of the Baffling Biological
J. Clin. Oncol.,
May 10, 2000;
18(10):
2007 - 2009.
[Full Text]
[PDF]
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C. P. Wong and R. Levy
Recombinant Adenovirus Vaccine Encoding a Chimeric T-Cell Antigen Receptor Induces Protective Immunity against a T-Cell Lymphoma
Cancer Res.,
May 1, 2000;
60(10):
2689 - 2695.
[Abstract]
[Full Text]
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J. M. Timmerman and R. Levy
Linkage of Foreign Carrier Protein to a Self-Tumor Antigen Enhances the Immunogenicity of a Pulsed Dendritic Cell Vaccine
J. Immunol.,
May 1, 2000;
164(9):
4797 - 4803.
[Abstract]
[Full Text]
[PDF]
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F. Osterroth, A. Garbe, P. Fisch, and H. Veelken
Stimulation of cytotoxic T cells against idiotype immunoglobulin of malignant lymphoma with protein-pulsed or idiotype-transduced dendritic cells
Blood,
February 15, 2000;
95(4):
1342 - 1349.
[Abstract]
[Full Text]
[PDF]
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J. Apostolidis, R. K. Gupta, D. Grenzelias, P. W. M. Johnson, V. I. Pappa, K. E. Summers, A. Salam, K. Adams, A. J. Norton, J. A. L. Amess, et al.
High-Dose Therapy With Autologous Bone Marrow Support as Consolidation of Remission in Follicular Lymphoma: Long-Term Clinical and Molecular Follow-Up
J. Clin. Oncol.,
February 1, 2000;
18(3):
527 - 527.
[Abstract]
[Full Text]
[PDF]
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J. E. Harris, L. Ryan, H. C. Hoover Jr, R. K. Stuart, M. M. Oken, A. B. Benson III, E. Mansour, D. G. Haller, J. Manola, and M. G. Hanna Jr
Adjuvant Active Specific Immunotherapy for Stage II and III Colon Cancer With an Autologous Tumor Cell Vaccine: Eastern Cooperative Oncology Group Study E5283
J. Clin. Oncol.,
January 5, 2000;
18(1):
148 - 148.
[Abstract]
[Full Text]
[PDF]
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F. Cabanillas, S. Horning, M. Kaminski, and R. Champlin
Managing Indolent Lymphomas in Relapse: Working Our Way Through a Plethora of Options
Hematology,
January 1, 2000;
2000(1):
166 - 179.
[Abstract]
[Full Text]
[PDF]
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R. Levy
Karnofsky Lecture: Immunotherapy of Lymphoma
J. Clin. Oncol.,
November 1, 1999;
17(90001):
7 - 12.
[Full Text]
[PDF]
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N. van Baren, F. Brasseur, D. Godelaine, G. Hames, A. Ferrant, F. Lehmann, M. Andre, C. Ravoet, C. Doyen, G. C. Spagnoli, et al.
Genes Encoding Tumor-Specific Antigens Are Expressed in Human Myeloma Cells
Blood,
August 15, 1999;
94(4):
1156 - 1164.
[Abstract]
[Full Text]
[PDF]
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M. Massaia, P. Borrione, S. Battaglio, S. Mariani, E. Beggiato, P. Napoli, C. Voena, A. Bianchi, M. Coscia, B. Besostri, et al.
Idiotype Vaccination in Human Myeloma: Generation of Tumor-Specific Immune Responses After High-Dose Chemotherapy
Blood,
July 15, 1999;
94(2):
673 - 683.
[Abstract]
[Full Text]
[PDF]
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L. S. Peng, M. L. Penichet, and S. L. Morrison
A Single-Chain IL-12 IgG3 Antibody Fusion Protein Retains Antibody Specificity and IL-12 Bioactivity and Demonstrates Antitumor Activity
J. Immunol.,
July 1, 1999;
163(1):
250 - 258.
[Abstract]
[Full Text]
[PDF]
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A. D. Syrengelas and R. Levy
DNA Vaccination Against the Idiotype of a Murine B Cell Lymphoma: Mechanism of Tumor Protection
J. Immunol.,
April 15, 1999;
162(8):
4790 - 4795.
[Abstract]
[Full Text]
[PDF]
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V. L. Reichardt, C. Y. Okada, A. Liso, C. J. Benike, K. E. Stockerl-Goldstein, E. G. Engleman, K. G. Blume, and R. Levy
Idiotype Vaccination Using Dendritic Cells After Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma---A Feasibility Study
Blood,
April 1, 1999;
93(7):
2411 - 2419.
[Abstract]
[Full Text]
[PDF]
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A. A. Shtil, J. G. Turner, J. Durfee, W. S. Dalton, and H. Yu
Cytokine-Based Tumor Cell Vaccine Is Equally Effective Against Parental and Isogenic Multidrug-Resistant Myeloma Cells: The Role of Cytotoxic T Lymphocytes
Blood,
March 15, 1999;
93(6):
1831 - 1837.
[Abstract]
[Full Text]
[PDF]
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R. Buhmann, A. Nolte, D. Westhaus, B. Emmerich, and M. Hallek
CD40-Activated B-Cell Chronic Lymphocytic Leukemia Cells for Tumor Immunotherapy: Stimulation of Allogeneic Versus Autologous T Cells Generates Different Types of Effector Cells
Blood,
March 15, 1999;
93(6):
1992 - 2002.
[Abstract]
[Full Text]
[PDF]
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C. P. Wong, C. Y. Okada, and R. Levy
TCR Vaccines Against T Cell Lymphoma: QS-21 and IL-12 Adjuvants Induce a Protective CD8+ T Cell Response
J. Immunol.,
February 15, 1999;
162(4):
2251 - 2258.
[Abstract]
[Full Text]
[PDF]
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A. A. McCormick, M. H. Kumagai, K. Hanley, T. H. Turpen, I. Hakim, L. K. Grill, D. Tuse, S. Levy, and R. Levy
Rapid production of specific vaccines for lymphoma by expression of the tumor-derived single-chain Fv epitopes in tobacco plants
PNAS,
January 19, 1999;
96(2):
703 - 708.
[Abstract]
[Full Text]
[PDF]
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K.-M. Chang, N. H. Gruener, S. Southwood, J. Sidney, G. R. Pape, F. V. Chisari, and A. Sette
Identification of HLA-A3 and -B7-Restricted CTL Response to Hepatitis C Virus in Patients with Acute and Chronic Hepatitis C
J. Immunol.,
January 15, 1999;
162(2):
1156 - 1164.
[Abstract]
[Full Text]
[PDF]
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H. K. Muller-Hermelink and A. Greiner
Molecular Analysis of Human Immunoglobulin Heavy Chain Variable Genes (IgVH) in Normal and Malignant B Cells
Am. J. Pathol.,
November 1, 1998;
153(5):
1341 - 1346.
[Full Text]
[PDF]
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T. A. Davis, D. G. Maloney, D. K. Czerwinski, T.-M. Liles, and R. Levy
Anti-Idiotype Antibodies Can Induce Long-Term Complete Remissions in Non-Hodgkin's Lymphoma Without Eradicating the Malignant Clone
Blood,
August 15, 1998;
92(4):
1184 - 1190.
[Abstract]
[Full Text]
[PDF]
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G. J. Randolph, S. Beaulieu, M. Pope, I. Sugawara, L. Hoffman, R. M. Steinman, and W. A. Muller
A physiologic function for p-glycoprotein (MDR-1) during the migration of dendritic cells from skin via afferent lymphatic vessels
PNAS,
June 9, 1998;
95(12):
6924 - 6929.
[Abstract]
[Full Text]
[PDF]
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C. B. Caspar, S. Levy, and R. Levy
Idiotype Vaccines for Non-Hodgkin's Lymphoma Induce Polyclonal Immune Responses That Cover Mutated Tumor Idiotypes: Comparison of Different Vaccine Formulations
Blood,
November 1, 1997;
90(9):
3699 - 3706.
[Abstract]
[Full Text]
[PDF]
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G. J. Weiner, H.-M. Liu, J. E. Wooldridge, C. E. Dahle, and A. M. Krieg
Immunostimulatory oligodeoxynucleotides containing the CpG motif are effective as immune adjuvants in tumor antigen immunization
PNAS,
September 30, 1997;
94(20):
10833 - 10837.
[Abstract]
[Full Text]
[PDF]
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M.-Y. Cao, F. Shinjo, S. Heinrichs, J.-W. Soh, J. Jongstra-Bilen, and J. Jongstra
Inhibition of Anti-IgM-induced Translocation of Protein Kinase C beta I Inhibits ERK2 Activation and Increases Apoptosis
J. Biol. Chem.,
June 29, 2001;
276(27):
24506 - 24510.
[Abstract]
[Full Text]
[PDF]
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