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: Eric F Zhu, Shuning A Gai, Cary F Opel, Byron H Kwan, Rishi Surana, Martin C Mihm, Monique J Kauke, Kelly D Moynihan, Alessandro Angelini, Robert T Williams, Matthias T Stephan, Jacob S Kim, Michael B Yaffe, Darrell J Irvine, Louis M Weiner, Glenn Dranoff, K Dane Wittrup
• Journal: Cancer cell (Cancer Cell) Vol. 27 Issue 4 Pg. 489-501 (Apr 13 2015) ISSN: 1878-3686 [Electronic] United States
• PMID: 25873172 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-2

Topics

• Adaptive Immunity
• Animals
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Drug Synergism
• Half-Life
• Immunity, Innate
• Immunotherapy
• Interleukin-2 (metabolism, pharmacokinetics, pharmacology)
• Killer Cells, Natural (drug effects, immunology)
• Mice
• Mice, Inbred C57BL
• Neoplasms (immunology, therapy)