[PDF][PDF] Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2

EF Zhu, SA Gai, CF Opel, BH Kwan, R Surana… - Cancer cell, 2015 - cell.com
EF Zhu, SA Gai, CF Opel, BH Kwan, R Surana, MC Mihm, MJ Kauke, KD Moynihan
Cancer cell, 2015cell.com
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 …
Summary
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.
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