Researchers say they’ve found a way to target myeloid-derived suppressor cells (MDSCs) while sparing other immune cells.
In preclinical experiments, the team showed they could deplete MDSCs—and shrink tumors—using peptide antibodies.
These “peptibodies” wiped out MDSCs in the blood, spleen, and tumor cells of mice without binding to other white blood cells or dendritic cells.
The researchers described this work in Nature Medicine.
“We’ve known about [MDSCs] blocking immune response for a decade but haven’t been able to shut them down for lack of an identified target,” said the paper’s senior author, Larry Kwak, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston.
“This is the first demonstration of a molecule on these cells that allows us to make an antibody—in this case, a peptide—to bind to them and get rid of them. It’s a brand new immunotherapy target.”
Dr Kwak and his colleagues began this research by applying a peptide phage library to MDSCs, which allowed for a mass screening of candidate peptides that bind to the surface of MDSCs. This revealed 2 peptides, labeled G3 and H6, that bound only to MDSCs.
The researchers fused the 2 peptides to a portion of mouse immune globulin to generate experimental peptibodies called pep-G3 and pep-H6. Both peptibodies bound to both types of MDSCs—monocytic and granulocytic cells.
Dr Kwak and his colleagues then tested the peptibodies in 2 mouse models of thymic tumors, as well as models of melanoma and lymphoma. The team compared pep-G3 and pep-H6 to a control peptibody and an antibody against Gr-1.
Both pep-G3 and pep-H6 depleted monocytic and granulocytic MDSCs in the blood and spleens of all mice. But the Gr-1 antibody only worked against granulocytic MDSCs.
To see whether MDSC depletion would impede tumor growth, the researchers administered the peptibodies to mice with thymic tumors every other day for 2 weeks.
Mice treated with either pep-G3 or pep-H6 had tumors that were about half the size and weight of those in mice treated with the control peptibody or the Gr-1 antibody.
Lastly, the researchers analyzed surface proteins on the MDSCs and found that S100A9 and S100A8 are the likely binding targets for pep-G3 and pep-H6.
Dr Kwak and his colleagues said they are now working to extend these findings to human MDSCs.
