Abstract SY06-02: Macrophage-targeted cancer immunotherapy

Abstract

Abstract Combining immunotherapies that harness cytotoxic T cells to fight cancer has become a major effort in treating metastatic cancer patients. We present data on an example of cancer immunotherapy combination targeting innate immune cells, in particular tumor-associated macrophages (TAMs), that is currently being tested in the clinic. Combination of a TAM-depleting anti-CSF-1R antibody with an activating anti-CD40 agonist demonstrated synergistic antitumoral efficacy resulting in complete tumor remission in preclinical mouse cancer models. Ex vivo RNA sequencing of sorted TAM revealed that only the combination treatment induced a transient, profound repolarization of TAMs towards an immunostimulatory M1 phenotype. However, these TAM populations are ultimately eliminated. The central role of macrophages was further substantiated by complete loss of therapeutic benefit when TAMs were depleted prior to combinational treatment. Furthermore, rechallenge and depletion experiments demonstrated that tumor rejection is finally mediated by an antitumoral T-cell response. In colorectal cancer patients coexpression of human CSF1R and CD40 on TAMs was detected, providing the basis to explore this combination in the clinic. Citation Format: Carola Ries. Macrophage-targeted cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY06-02. doi:10.1158/1538-7445.AM2017-SY06-02