Abstract
Available therapies for lymphoplasmacytic lymphoma (LPL) provide no survival advantage if started before signs or symptoms of end-organ damage develop; hence, current recommendations are to follow a program of observation while patients are in the asymptomatic phase of disease. We hypothesize that using idiotypic determinants of a B-cell lymphoma’s surface immunoglobulin as a tumor-specific marker, we can develop patient-specific chemokine-idiotype fusion DNA vaccines that induce an immune response against LPL. By activating the host immune system against the tumor antigen, we postulate that disease control of asymptomatic phase lymphoplasmacytic lymphoma can be maintained. These chemokine-idiotype fusion DNA vaccines provide protection in a lymphoma mouse model and have recently entered clinical trials. Herein, we describe procedures for the generation of therapeutic vaccines, particularly “second-generation” recombinant vaccines. Specifically, in the Methods section we describe how to identify lymphoma-associated immunoglobulin V (IgV) genes from patient biopsy and how to assemble these genes as single-chain variable gene fragment (scFv) in-frame with MIP-3α to generate novel DNA fusion vaccines.
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References
Schuster SJ et al (2011) Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. J Clin Oncol 29:2787–2794
Biragyn A et al (1999) Genetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent antitumor immunity. Nat Biotechnol 17:253–258
Biragyn A et al (2004) Chemokine receptor-mediated delivery directs self-tumor antigen efficiently into the class II processing pathway in vitro and induces protective immunity in vivo. Blood 104:1961–1969
Dimopoulos MA et al (2005) Diagnosis and management of Waldenstrom’s macroglobulinemia. J Clin Oncol 23:1564–1577
Dimopoulos MA et al (2009) Update on treatment recommendations from the Fourth International Workshop on Waldenstrom’s macroglobulinemia. J Clin Oncol 27:120–126
Tiller T et al (2008) Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J Immunol Methods 329:112–124
Kobrin CB, Kwak LW (1997) Development of vaccine strategies for the treatment of B-cell malignancies. Cancer Invest 15:577–587
Mahvi DM et al (2007) Intratumoral injection of IL-12 plasmid DNA—results of a phase I/IB clinical trial. Cancer Gene Ther 14:717–723
Lee SW et al (2000) Development of a polynucleotide vaccine from melanoma antigen recognized by T cells-1 and recombinant protein from melanoma antigen recognized by T cells-1 for melanoma vaccine clinical trials. J Immunother 23:379–386
Korbie DJ, Mattick JS (2008) Touchdown PCR for increased specificity and sensitivity in PCR amplification. Nat Protoc 3:1452–1456
Acknowledgement
This work was supported by the Cancer Prevention and Research Institute of Texas.
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Cha, Sc., Qin, H., Sakamaki, I., Kwak, L. (2014). Cloning Variable Region Genes of Clonal Lymphoma Immunoglobulin for Generating Patient-Specific Idiotype DNA Vaccine. In: Lawman, M., Lawman, P. (eds) Cancer Vaccines. Methods in Molecular Biology, vol 1139. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0345-0_24
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DOI: https://doi.org/10.1007/978-1-4939-0345-0_24
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Publisher Name: Humana Press, New York, NY
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