Synergistic Innate and Adaptive Immune Response to Combination Immunotherapy with Anti-Tumor Antigen Antibodies and Extended Serum Half-Life IL-2
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Yaffe_Synergistic innate.pdf
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Author(s)
Surana, Rishi
Mihm, Martin C.
Angelini, Alessandro
Weiner, Louis M.
Dranoff, Glenn
Zhu, Eric Franklin
Opel, Cary Francis
Kwan, Byron Hua
Kauke, Monique Jacqueline
Moynihan, Kelly Dare
Date Issued
April 2015
Journal
Cancer Cell
Publisher
Elsevier
Citation
Zhu, Eric F. et al. “Synergistic Innate and Adaptive Immune Response to Combination Immunotherapy with Anti-Tumor Antigen Antibodies and Extended Serum Half-Life IL-2.” Cancer Cell 27.4 (2015): 489–501.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Center for Materials Science and Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.ccell.2015.03.004
