GB1275, a first-in-class CD11b modulator: rationale for immunotherapeutic combinations in solid tumors.

ABSTRACT: Resistance to immune checkpoint inhibitors (ICI) and other anticancer therapies is often associated with the accumulation of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Therefore, targeting MDSC recruitment or function is of significant interest as a strategy to treat patients with ICI-resistant cancer. The migration and recruitment of MDSCs to the TME is mediated in part by the CD11b/CD18 integrin heterodimer (Mac-1; α_Mβ₂), expressed on both MDSCs and TAMs. However, inhibition or blockade of CD11b/CD18 has had limited success in clinical trials to date, likely since saturation of CD11b requires doses that are not clinically tolerable with the agents tested so far. Interestingly, activation of C

SUBMITTER: DeNardo DG 

PROVIDER: S-EPMC8404448 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature