title: Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2.
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.
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Eric F
authors: EF
authors: Zhu
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Shuning A
authors: SA
authors: Gai
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Cary F
authors: CF
authors: Opel
authors: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Byron H
authors: BH
authors: Kwan
authors: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
authors: Rishi
authors: R
authors: Surana
authors: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02214, USA.
authors: Martin C
authors: MC
authors: Mihm
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Monique J
authors: MJ
authors: Kauke
authors: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Kelly D
authors: KD
authors: Moynihan
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Alessandro
authors: A
authors: Angelini
authors: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Robert T
authors: RT
authors: Williams
authors: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Matthias T
authors: MT
authors: Stephan
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Jacob S
authors: JS
authors: Kim
authors: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Michael B
authors: MB
authors: Yaffe
authors: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA 02129, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors: Darrell J
authors: DJ
authors: Irvine
authors: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
authors: Louis M
authors: LM
authors: Weiner
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors: Glenn
authors: G
authors: Dranoff
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: wittrup@mit.edu.
authors: K Dane
authors: KD
authors: Wittrup
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004357:Drug Synergism; D006207:Half-Life; D007113:Immunity, Innate; D007167:Immunotherapy; D007376:Interleukin-2 / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D007376:Interleukin-2