Abstract
The burden of breast cancer is imposing a huge global problem. Drug discovery research and novel approaches to treat breast cancer have been carried out extensively over the last decades. Although immune checkpoint inhibitors are showing promising preclinical and clinical results in treating breast cancer, they are facing multiple limitations. From an immunological perspective, a recent report highlighted breast cancer as an “inflamed tumor” with an immunosuppressive microenvironment. Consequently, researchers have been focusing on identifying novel immunological targets that can tune up the tumor immune microenvironment. In this context, several novel non-classical immune targets have been targeted to determine their ability to uncouple immunoregulatory pathways at play in the tumor microenvironment. This article will highlight strategies designed to increase the immunogenicity of the breast tumor microenvironment. It also addresses the latest studies on targets which can enhance immune responses to breast cancer and discusses examples of preclinical and clinical trial landscapes that utilize these targets.
Highlights
The Global Cancer Statistics (GLOBOCAN 2018) report of 2018 flags breast cancer as the second most diagnosed cancer, with a prevalence of ∼11.6% of all cancer cases [1]
A clinical study that had planned to test the agonistic anti-OX40 antibody, MEDI6469, in combination with immune checkpoint inhibitors in patients diagnosed with advanced solid tumors, was terminated [32, 35, 36]
Another phase I/II study, which investigated the use of MEDI6469 in combination with radiation for the treatment of metastatic breast cancer has been completed (ClinicalTrials.gov Identifier: NCT01862900)
Summary
The Global Cancer Statistics (GLOBOCAN 2018) report of 2018 flags breast cancer as the second most diagnosed cancer, with a prevalence of ∼11.6% of all cancer cases [1]. A clinical study that had planned to test the agonistic anti-OX40 antibody, MEDI6469, in combination with immune checkpoint inhibitors in patients diagnosed with advanced solid tumors, was terminated [32, 35, 36]. Another phase I/II study, which investigated the use of MEDI6469 in combination with radiation for the treatment of metastatic breast cancer has been completed (ClinicalTrials.gov Identifier: NCT01862900). An additional phase I study has been initiated to investigate the effectiveness of using a CD40 agonist, ABBV-927 plus OX40 agonist ABBV368 in combination or without the PD1 inhibitor, budigalimab in patients with advanced solid tumors, including TNBC (ClinicalTrials.gov Identifier: NCT03893955).
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