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

TitleSynergistic Innate and Adaptive Immune Response to Combination Immunotherapy with Anti-Tumor Antigen Antibodies and Extended Serum Half-Life IL-2
Publication TypeJournal Article
Year of Publication2015
AuthorsZhu, 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
JournalCancer Cell
Volume27
Issue4
Pagination489 - 501
Date Published2015/04/13/
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.