Novel immune checkpoint receptor identified using Retrogenix
A recent paper, published in the journal Cancer Immunology Research, describes the discovery of a novel inhibitory receptor for the immune checkpoint protein HHLA2. This newly characterised interaction contributes to tumour immune evasion independently to the PD-1/PD-L1 pathway and presents a promising target in the development of novel immunotherapies.
HHLA2, a member of the B7 immune checkpoint family, has co-stimulatory and co-inhibitory effects on the T cell response. The co-stimulatory effects of HHLA2 are due to its interaction with the CD28 family member, TMIGD2 (CD28H); however, the co-inhibitory receptor for HHLA2 was previously unknown.
Using the Retrogenix cell microarray technology, a soluble human HHLA2-Ig fusion protein was screened against a large proprietary library of plasma membrane and secreted proteins. The screen identified a novel interaction with KIR3DL3, a member of the KIR family of inhibitory receptors, which was later confirmed to be an immunoinhibitory checkpoint receptor for HHLA2.
Identifying KIR3DL3 as a HHLA2 receptor has allowed for the development of new checkpoint inhibitor antibodies that have potential as immune therapies, either alone or in combination with PD1 inhibitors.
The research was led by scientists at Dana-Faber Cancer Institute in collaboration with Retrogenix, Beth Israel Deaconess Medical Center, BPS Bioscience, MIT, and Harvard Medical School. Click here to link to the abstract and full text options.
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