A BCR/ABL-hIL-2 DNA Vaccine Enhances the Immune Responses in BALB/c Mice

Yanan Qin,Yangqiu Li,Hongxia Tian,Chen Lin,Guanming Wang

doi:10.1155/2013/136492

Yanan Qin, Yangqiu Li + Show 3 more

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https://doi.org/10.1155/2013/136492

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Abstract

The use of a DNA vaccine encoding the BCR/ABL fusion gene is thought to be a promising approach for patients with chronic myeloid leukemia (CML) to eradicate minimal residual disease after treatment with chemotherapy or targeted therapy. In this study, our strategy employs genetic technology to create a DNA vaccine encoding the BCR/ABL fusion and human interleukin-2 (hIL-2) genes. The successfully constructed plasmids BCR/ABL-pIRES-hIL-2, BCR/ABL-pIRES, and pIRES-hIL-2 were delivered intramuscularly to BALB/c mice at 14-day intervals for three cycles. The transcription and expression of the BCR/ABL and hIL-2 genes were found in the injected muscle tissues. The interferon-γ (IFN-γ) serum levels were increased, and the splenic CD4+/CD8+ T cell ratio was significantly decreased in the BCR/ABL-pIRES-hIL-2-injected mice. Furthermore, specific antibodies against K562 cells could be detected by indirect immunofluorescence. These results indicate that a DNA vaccine containing BCR/ABL and hIL-2 together may elicit increased in vivo humoral and cellular immune responses in BALB/c mice.

Highlights

Chronic myeloid leukemia (CML), with an incidence of 1.5/100,000 people, represents 15% of newly diagnosed leukemia cases in adults in China
The IFN-γ level of mice immunized with BCR/ABLpIRES-human interleukin-2 (hIL-2) was higher than that of the BCR/ABL-pIRES and pIRES-hIL-2 groups (P < 0.05)
The use of DNA vaccines has demonstrated the feasibility of using DNA vaccines to induce antigen-specific immune responses targeting tumor cells in preclinical and clinical trials [18, 25,26,27]

Summary

Introduction

Chronic myeloid leukemia (CML), with an incidence of 1.5/100,000 people, represents 15% of newly diagnosed leukemia cases in adults in China. The Philadelphia chromosomal translocation t(9;22)(q34;q11) is essential to its pathogenesis and is found in approximately 95% of patients with CML. The result of this translocation is the BCR-ABL fusion protein, which is associated with the increased ABL tyrosine kinase activity that is directly associated with leukemogenesis [1]. Imatinib mesylate (IM), which is an inhibitor of BCRABL-coded tyrosine kinase activity, is the first drug widely used to treat CML. A number of patients with CML die due to ABL mutation-related drug resistance and blast crisis because IM does not kill leukemia stem cells (LSCs), which persist in a majority of patients and may cause disease relapse, and clinical resistance may develop predominantly due to point mutations in the ABL kinase domain [2]. Novel tyrosine kinase inhibitors have been developed to solve the mutation problem [3, 4]; their binding specificity and target profiles have not been readily predicted in pathological and normal cells [5, 6]

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