Synergistic Innate and Adaptive Immune Response to Combination Immunotherapy with Anti-Tumor Antigen Antibodies and Extended Serum Half-Life IL-2

• Main Authors: Surana, Rishi (Author), Mihm, Martin C (Author), Angelini, Alessandro (Contributor), Weiner, Louis M (Author), Dranoff, Glenn (Author), Zhu, Eric Franklin (Contributor), Opel, Cary Francis (Contributor), Kwan, Byron Hua (Contributor), Kauke, Monique Jacqueline (Contributor), Moynihan, Kelly Dare (Contributor), Williams, Robert T. (Contributor), Yaffe, Michael B (Contributor), Irvine, Darrell J (Contributor), Wittrup, Karl Dane (Contributor), Gai, S. Annie (Author), Stephan, Matthias T. (Author), Kim, Jacob S. (Author)
• Other Authors: Massachusetts Institute of Technology. Center for Materials Science and Engineering (Contributor), Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor), Gai, Shuning (Contributor), Stephan, Matthias (Contributor), Kim, Jacob S (Contributor)
• Format: Article
• Language: English
• Published: Elsevier, 2016-12-15T19:25:49Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Cancer Institute (U.S.) (Grant NCI CA174795)
National Institute of General Medical Sciences (U.S.). Biotechnology Training Program
National Science Foundation (U.S.). Graduate Research Fellowship Program