Cancer Cell
Volume 27, Issue 4, 13 April 2015, Pages 489-501
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Article
Synergistic Innate and Adaptive Immune Response to Combination Immunotherapy with Anti-Tumor Antigen Antibodies and Extended Serum Half-Life IL-2

https://doi.org/10.1016/j.ccell.2015.03.004Get rights and content
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Highlights

  • Serum-persistent IL-2 and anti-tumor IgG induces strong control of tumor growth

  • Immune response includes a cytokine storm with high levels of MIP-2, IFNγ, and IL-6

  • Neutrophils drive efficacy, and infiltration is mediated by NK cells and macrophages

  • Adoptive transfer of CD8+ T cells, Fc/IL-2, and antibody confers long-term efficacy

Summary

Cancer immunotherapies under development have generally focused on either stimulating T cell immunity or driving antibody-directed effector functions of the innate immune system such as antibody-dependent cell-mediated cytotoxicity (ADCC). We find that a combination of an anti-tumor antigen antibody and an untargeted IL-2 fusion protein with delayed systemic clearance induces significant tumor control in aggressive isogenic tumor models via a concerted innate and adaptive response involving neutrophils, NK cells, macrophages, and CD8+ T cells. This combination therapy induces an intratumoral “cytokine storm” and extensive lymphocyte infiltration. Adoptive transfer of anti-tumor T cells together with this combination therapy leads to robust cures of established tumors and development of immunological memory.

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