Title | Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Zhu EF, Gai SA, Opel CF, Kwan BH, Surana R, Mihm MC, Kauke MJ, Moynihan KD, Angelini A, Williams RT, Stephan MT, Kim JS, Yaffe MB, Irvine DJ, Weiner LM, Dranoff G, K Wittrup D |
Journal | Cancer Cell |
Volume | 27 |
Issue | 4 |
Pagination | 489-501 |
Date Published | 2015 Apr 13 |
ISSN | 1878-3686 |
Keywords | Adaptive Immunity, Animals, CD8-Positive T-Lymphocytes, Drug Synergism, Half-Life, Immunity, Innate, Immunotherapy, Interleukin-2, Killer Cells, Natural, Mice, Mice, Inbred C57BL, Neoplasms |
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. |
DOI | 10.1016/j.ccell.2015.03.004 |
Alternate Journal | Cancer Cell |
PubMed ID | 25873172 |
PubMed Central ID | PMC4398916 |
Grant List | P30 CA014051 / CA / NCI NIH HHS / United States R01 CA050633 / CA / NCI NIH HHS / United States T32 GM008334 / GM / NIGMS NIH HHS / United States R01 CA174795 / CA / NCI NIH HHS / United States / / Intramural NIH HHS / United States T32 CA009686 / CA / NCI NIH HHS / United States CA174795 / CA / NCI NIH HHS / United States |
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