Peptide blocker of myeloid checkpoint; plus a magnet-based device to collect circulating tumor cells, severe vs. mild COVID-19 immune cell profiles and more
Macrocyclic don’t-eat-me signal blocker
A Japan-based team has reported in Cell Chemical Biology the development of a macrocyclic peptide that allosterically blocks the CD47-SIRPA myeloid checkpoint. The 15-residue peptide binds mouse SIRPA, and in a mouse model of melanoma enhanced an anti-TYRP1 antibody-mediated reduction in lung metastases. Combining the peptide with anti-CD20 mAb rituximab led to augmented inhibition of tumor growth and prolonged survival in a xenograft mouse model of lymphoma.
Over 10 companies are developing inhibitors of the pathway; the most advanced is anti-CD47 mAb magrolimab from Gilead Sciences Inc. (NASDAQ:GILD), which gained the program through its $4.9 billion acquisition of Forty Seven Inc. in March (see “Gilead Takes Out Forty Seven”)...