Targeted DNA vaccines eliciting crossreactive anti-idiotypic antibody responses against human B cell malignancies in mice

Ruffini, Pier Adelchi, Os, Audun, Dolcetti, Riccardo, Tjonnfjord, Geir E., Munthe, Ludvig A. and Bogen, Bjarne (2014) Targeted DNA vaccines eliciting crossreactive anti-idiotypic antibody responses against human B cell malignancies in mice. Journal of Translational Medicine, 12 207: 1-12. doi:10.1186/1479-5876-12-207


Author Ruffini, Pier Adelchi
Os, Audun
Dolcetti, Riccardo
Tjonnfjord, Geir E.
Munthe, Ludvig A.
Bogen, Bjarne
Title Targeted DNA vaccines eliciting crossreactive anti-idiotypic antibody responses against human B cell malignancies in mice
Journal name Journal of Translational Medicine   Check publisher's open access policy
ISSN 1479-5876
Publication date 2014-07-25
Sub-type Article (original research)
DOI 10.1186/1479-5876-12-207
Open Access Status DOI
Volume 12
Issue 207
Start page 1
End page 12
Total pages 12
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background
Therapeutic idiotypic (Id) vaccination is an experimental treatment for selected B cell malignancies. A broader use of Id-based vaccination, however, is hampered by the complexity and costs due to the individualized production of protein vaccines. These limitations may be overcome by targeted DNA vaccines encoding stereotyped immunoglobulin V regions of B cell malignancies. We have here investigated whether such vaccines might elicit cross-reactive immune responses thus offering the possibility to immunize subsets of patients with the same vaccine.

Methods
Fusion vaccines targeting patient Id to mouse Major Histocompatibility Complex (MHC) class II molecules (chimeric mouse/human) or chemokine receptors (fully human) on antigen-presenting cells (APC) were genetically constructed for two Chronic Lymphocytic Leukemia (CLL) patients and one prototypic stereotyped B-cell receptor (BCR) commonly expressed by Hepatitis C Virus (HCV)-associated Non Hodgkin Lymphoma (NHL). The A20 murine B lymphoma cells were engineered to express prototypic HCV-associated B cell lymphoma BCR. Anti-Id antibody responses were studied against stereotyped and non-stereotyped BCRs on CLL patients’ cells as well as transfected A20 cells.

Results
DNA vaccination of mice with Id vaccines that target APC elicited increased amounts of antibodies specific for the patient’s Id as compared with non targeted control vaccines. Anti–Id antibodies cross-reacted between CLL cells with closely related BCR. A20 cells engineered to express patients’ V regions were not tumorigenic in mice, preventing tumor challenge experiments.

Conclusions
These findings provide experimental support for use of APC-targeted fusion Id DNA vaccines for the treatment of B cell lymphoma and CLL that express stereotyped BCRs.
Keyword Lymphoma
Cancer vaccine
Idiotype
Chemokine
CLL
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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