Anti-tumor effect of DNA-based vaccination and dSLIM immunomodulatory molecules in mice with Ph+ acute lymphoblastic leukaemia

Abstract Since the prognosis of patients with Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) still remains poor, new relapse prevention strategies are needed. We evaluated the pre-immunization of mice with DNA-based vaccines subsequently challenged by the syngeneic Ph+ ALL...

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Bibliographic Details
Published in:Vaccine 2008-08, Vol.26 (36), p.4669-4675
Main Authors: Köchling, Joachim, Prada, Javier, Bahrami, Masoud, Stripecke, Renata, Seeger, Karl, Henze, Günter, Wittig, Burghardt, Schmidt, Manuel
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
Applied microbiology
Biological and medical sciences
Bone marrow
Cancer Vaccines - immunology
Cell Line, Tumor
Confidence intervals
Cytokines
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA vaccination
Experiments
Female
Fundamental and applied biological sciences. Psychology
Gene expression
Genetic Vectors
Immunization
Immunologic Factors - administration & dosage
Leukemia
Medical sciences
Mice
Mice, Inbred BALB C
Microbiology
Peptides
Ph + ALL
Polynucleotides - administration & dosage
Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
Precursor Cell Lymphoblastic Leukemia-Lymphoma - prevention & control
Proteins
Secondary Prevention
Survival Analysis
Syngeneic mouse model
Transfection - methods
Tumors
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, DNA - immunology
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Summary:Abstract Since the prognosis of patients with Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) still remains poor, new relapse prevention strategies are needed. We evaluated the pre-immunization of mice with DNA-based vaccines subsequently challenged by the syngeneic Ph+ ALL cell line BM185. Ballistic transfer of minimalistic immunogenically defined gene expression (MIDGE) vectors encoding a BCR-ABLp185 fusion specific peptide or GM–CSF were used for in vivo transfection. DNA-based double stem–loop immunomodulators (dSLIM) were used as immune adjuvant. We present survival and functional data that DNA-based vaccination with BCR-ABLp185 fusion specific sequences, GM–CSF and dSLIM leads to an anti-tumor effect in mice challenged with a lethal Ph+ ALL dose and this effect depends on leukaemia-specific sequences.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2008.06.094