Related Experiment Videos
Immunoregulation by B7 and IL-12 gene transfer
1Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Leukemia
|April 1, 1997
Summary
Combination gene therapy using B7 costimulatory molecules and interleukin-12 (IL-12) significantly reduced lung metastasis in mice. This approach enhances antitumor immunity, offering potential for treating metastatic cancers.
Area of Science:
- Immunology
- Oncology
- Gene Therapy
Background:
- Antitumor effects can be induced by costimulatory molecules like B7.
- Interleukin-12 (IL-12) is a cytokine with potential in cancer therapy.
Purpose of the Study:
- To investigate the combination therapy of B7 costimulatory gene and IL-12 gene for treating metastatic mouse lung carcinoma.
- To clarify the in vivo biological functions of the IL-12 p40 subunit.
Main Methods:
- Transfection of mouse lung carcinoma 3LL cells with mouse B7 and/or IL-12 genes.
- Generation of transfectants: IL-12/3LL, B7/3LL, and IL-12/B7/3LL.
- Generation of myoblast transfectants producing IL-12 p40 alone.
Main Results:
- IL-12/B7/3LL inoculation significantly increased CTL activity (approx. 10-fold) compared to parental 3LL.
- Post-inoculation with IL-12/B7/3LL significantly reduced lung metastasis four weeks after 3LL inoculation.
- Local IL-12 p40 production suppressed allogeneic CTL induction and Th1-type antibody production in vivo.
- IL-12 p40 producing myoblasts showed reduced susceptibility to rejection.
Conclusions:
- Combination therapy with B7 and IL-12 genes induces potent therapeutic antitumor immunity against metastatic lung tumors.
- IL-12 p40 gene transfer may offer therapeutic benefits for Th1-mediated transplantation and autoimmune disorders.