ArticleTranslational cancer research2025
Engineered macrophages accumulate in solid tumors and locally deliver immune-activating proteins to inhibit tumor progression.
Article in Translational cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Currently, immune checkpoint inhibitors (ICIs) and other immune-activating strategies represent the main approach to cancer treatment; however, immune resistance in many solid tumors limits the immune therapy response and can cause strong toxic side effects. In solid tumors, the development of effective anti-tumor immune responses is hindered by limited immune cell infiltration and an immunosuppressive tumor microenvironment (TME). To overcome current immunotherapy challenges, we proposed a novel approach providing local and stable treatment levels to activate or revitalize anti-tumor immunity, to achieve the effect of TME infiltration and sustained presence in solid tumors. Methods: Using genetic engineering methods to synergistically activate immunity in the TME, we programmed macrophages to express therapeutic payloads, including interleukin (IL)-12 and the signal regulatory protein alpha-Fragment crystallizable fusion protein (SIRPα-Fc), a CD47 ICI. Co-culture studies were performed to evaluate the effects of the genetically engineered macrophages (GEMs) on the T cells and GEMs themselves Results: The IL-12 secreted by the GEMs provided effector signals for T cells, thereby enhancing the tumor resident anti-tumor macrophages and CD8 Conclusions: Our study showed the potential clinical application of GEMs in the treatment of tumors.
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