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Interleukin‐12 immunotherapy in a murine model of leukemia
Author(s) -
Nelles Megan Elizabeth,
Labbe Alain,
Walia Jagdeep,
Jia Lintao,
Furlonger Caren,
aka Takahiro,
Medin Jeffrey A.,
Paige Christopher J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.516
Subject(s) - ctl* , cytotoxic t cell , cd8 , immunotherapy , immunology , cancer research , systemic administration , t cell , population , medicine , interleukin 2 , antigen , in vivo , biology , immune system , in vitro , biochemistry , microbiology and biotechnology , environmental health
To improve the efficacy of interleukin‐12 (IL‐12) therapy using different dosage and administration protocols than those previously used in clinic, a model of murine acute lymphoblastic leukemia (ALL) was developed employing the well‐characterized cell line 70Z/3. Administration of low dose IL‐12 by two separate methods each led to efficient tumor clearance but by way of distinct mechanisms. Direct IL‐12 administration resulted in tumor rejection by the canonical pathway, ultimately mediated by CD8 + cytotoxic T lymphocytes (CTL). However, when 70Z/3 cells themselves were transduced with a novel lentiviral vector system to express IL‐12, in vivo depletion experiments demonstrated that a CD4 + cell population alone was absolutely required for tumor rejection but not CD8 + CTLs. We also observed that the outcome of therapy is dependent more on the number and quality of cellular interactions than on the absolute amount of IL‐12 administered. An example of such a cellular interaction might be that of an IL‐12 secreting tumor cell with an antigen presenting cell, a dendritic cell or macrophage, which subsequently interacts with a CD4 + cell to induce an effector response. For this interaction to be effective, the tumor cell must produce IL‐12 above a certain threshold. Overall, our studies highlight that the method of IL‐12 administration can have a significant impact on the outcome of treatment.