|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|
|Pagination||489 - 501|
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.