Enhancing the Delivery of Checkpoint Inhibitors in Patients with AML
In mice models, the systemic delivery of blood platelets that were coated with anti-PD-1 antibodies and conjugated to HSCs halted the recurrence of leukemia.
It may be possible to improve the use of checkpoint inhibitors through a novel combination approach in patients with acute myeloid leukemia (AML), according to research published in Nature Biomedical Engineering.1 In this study, researchers reported that conjugation of hematopoietic stem cells (HSCs) and platelets coated with anti-PD-1 antibodies may help improve antileukemia therapies.
Quanyin Hu, a PhD student in the department of bioengineering, University of California, Los Angeles, and colleagues noted that patients with AML who relapse following therapy have few treatment options. In addition, it is well documented that these patients face poor outcomes. In recent years, it has been shown that immune checkpoint inhibition by antibody-mediated programmed death-1 (PD-1) blockade may help improve outcomes in select patients with AML.
In the current study, Hu and colleagues demonstrated that the systemic delivery of blood platelets that are coated with anti-PD-1 antibodies and conjugated to HSCs has the ability to halt the progression and recurrence of leukemia in mice models.
First, the researchers injected leukemia cells into mice. Later, they found that the HSC–platelet–aPD-1 conjugate migrated to the bone marrow and locally released aPD-1. This enhanced the antileukemic immune responses in mice and extended their survival.
The researchers further found that this approach was able to increase the number of active T cells, cytokines, and chemokines. This novel cellular conjugate approach also promoted resistance when the mice were rechallenged with new leukemia cells. The authors wrote that this enhanced delivery of a checkpoint inhibitor may represent a promising new avenue of treatment.
- Hu Q, Sun W, Wang J, et al. Conjugation of haematopoietic stem cells and platelets decorated with anti-PD-1 antibodies augments anti-leukaemia efficacy. Nature Biomed Eng. 2018;2:831–840.