Serum-persistent IL-2 and anti-tumor IgG induces strong control of tumor growth
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Immune response includes a cytokine storm with high levels of MIP-2, IFNγ, and IL-6
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Neutrophils drive efficacy, and infiltration is mediated by NK cells and macrophages
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Adoptive transfer of CD8+ T cells, Fc/IL-2, and antibody confers long-term efficacy
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.