Editors' ChoiceCancer Immunotherapy

Straight Shooters: Peptibodies Take Aim

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Science Translational Medicine  11 Jun 2014:
Vol. 6, Issue 240, pp. 240ec102
DOI: 10.1126/scitranslmed.3009590

As a first line of defense, the immune system naturally attacks cancer cells. Lucky for cancer, there are cells in the tumor microenvironment that suppress these immune responses, interfering with the activation and proliferation of T cells specific for cancer. Because these suppressor cells often share surface markers with harmless blood cells, it is difficult to remove them from the body—and restore the anticancer immune response—without causing adverse side effects.

In a recent paper, Qin et al. described a way to eliminate such negative regulatory cells by using peptides that do not harm other cell types. Their focus was the heterogeneous population of myeloid-derived suppressor cells (MDSCs) that accelerates tumor progression by inhibiting T cell activation and promoting angiogenesis and metastasis. The team applied a peptide phage library to mass-screen for candidate peptides that bound only to the surface of MDSCs. Two identified peptides were then fused to the Fc region of mouse antibodies to generate what the authors called “peptibodies.” Qin and colleagues discovered that these peptibodies depleted MDSCs in the blood, spleen, and tumors of mice more effectively than did conventional antibodies targeting the myeloid differentiation antigen Gr-1—and without harming other vital cells. The researchers treated mice with two types of thymus tumor. In both cancer models, mice injected with peptibodies every other day for 2 weeks had tumors that were about half the size of those treated with control antibodies.

At this point, it is unclear whether this technique can be extended to identify and incorporate similar ligands on human immune suppressor cells. But given the broad range of cell types that dampen immune responses in cancer, these findings could provide a conceptual framework for the design of an entire repertoire of new peptibody-based immunotherapy drugs. The full potential of these previously unknown anticancer agents may only be realized when they are combined with therapies that stimulate anticancer immunity, such as vaccines, T cell therapy, costimulatory antibodies, or anti-checkpoint blockade.

H. Qin et al., Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice. Nat. Med. 10.1038/nm.3560 (2014). [Abstract]

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