Tumor-associated macrophages (TAMs) exist in nearly all
tumors, and form a major part of the tumor microenvironment. TAMs are divided into two groups:
tumor-suppressing M1 type and
tumor-promoting M2 type. Most TAMs are educated by the
tumor cells to become M2 type, which support
tumor growth and make
immunotherapy ineffective. Antibody-dependent cellular phagocytosis (ADCP) is an important mechanism for antibody
cancer therapy, and this mechanism is dependent on TAMs. In this study, we found that the M1 type macrophages elicit a more efficient ADCP response than the M2 type, which was confirmed by three tumor cell lines, Raji, A431, and SKBR3, along with their corresponding therapeutic antibody
Rituximab, anti-EGFR mouse
monoclonal antibody (clone 528), and
Trastuzumab, respectively.
Resiquimod (R848), an immune system activating agent, has been shown to stimulate the M1 type macrophages, and re-educate the TAMs from M2 type to M1 type. By treating TAMs with R848, the ADCP response increased significantly in vitro and in in vivo mouse xenograft models. R848 encapsulated
liposomes (R848-LPs) not only accumulated efficiently in the
tumor tissues, but also distributed in the TAMs. Synergizing the R848-LPs with the anti-EGFR mouse
monoclonal antibody (clone 528) significantly inhibited WiDr-
tumor growth in vivo. Our study also revealed that the TAM-targeted delivery of R848 is able to re-educate the TAMs to M1 type, enhance the ADCP effect of the
antibodies, and hence, enhance the anti-
tumor effect of the therapeutic
antibodies.