Posted: Monday, August 29, 2022
Using albumin-encapsulated nanoparticles containing the PI3Kγ inhibitor IPI-549 and paclitaxel (Nano-PI) in combination with anti–PD-1 antibodies to modulate the immune microenvironment in both lymph nodes and tumors led to long-term remission in two mouse models of metastatic triple-negative breast cancer, according to Duxin Sun, PhD, of the Rogel Cancer Center, University of Michigan, Ann Arbor, and colleagues. These results, which were published in Science Translational Medicine, also suggested this method of drug delivery may improve the efficacy of treatment.
“Immunomodulators that remodel the tumor immunosuppressive microenvironment have been combined with [anti–PD-1 and anti–PD-L1 antibodies] but have shown limited success in clinical trials; however, therapeutic strategies to modulate the immunosuppressive microenvironment of lymph nodes have been largely overlooked,” the investigators commented. “[Nano-PI in combination with anti–PD-1 antibodies] represents a promising candidate for future clinical trials.”
According to the investigators, this combination therapy achieved long-term remission in mouse models and eliminated lung metastases. Combining paclitaxel with IPI-549 was found to enable the formation of a stable nanoparticle and enhance the repolarization of immunosuppressive M2 macrophages to immune-promoting M1 macrophages.
In addition to enhancing the delivery of both immunomodulators to lymph nodes and tumors, IPI-549 plus paclitaxel seemed to improve the drug accumulation in the macrophages of these two tissues. Based on the results of immune cell profiling, the combination of IPI-549 plus paclitaxel with anti–PD-1 antibodies remodeled the immune microenvironment by polarizing M2 to M1 macrophages; increasing CD4-positive and CD8-positive T cells, B cells, and dendritic cells; decreasing regulatory T cells; and preventing T-cell exhaustion.
Disclosure: For full disclosures of the study authors, visit science.org.