PD1 Blocking Mouse Monoclonal Antibody [3A11]

Function

PD-1 blockade works during the effector phase to restore the immune function of T cells in the periphery that have been turned off following extended or high levels of antigen exposure, as in advanced cancer. The ligands for PD-1 can be expressed by tumor cells as well as tumor-infiltrating immune cells. PD-L1 expression on tumor cells varies by tumor type and also within a given tumor type, but appears to be particularly abundant in melanoma, non–small cell lung cancer (NSCLC), and ovarian cancer. In a recent study, PD-L1 expression on tumor cells was shown to be significantly associated with PD-1 expression on TILs, and was locally associated with PD-L2 expression when this ligand was also expressed. In the same study, tumor PD-L1 expression was the single factor most closely correlated with response to anti-PD-1 blockade, whereas PD-L1 expression on TILs was not associated with response. patient response to anti-PD-L1 blockade was strongest when PD-L1 was expressed by tumor-infiltrating immune cells. This antibody recognizing the PD-L1 binding region of PD1.

Background References

1. Sato Y et al. The PD-1/PD-L1 axis may be aberrantly activated in occupational cholangiocarcinoma. Pathol Int 67(3):163-170 (2017).

2. Buchbinder EI et al. CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. Am J Clin Oncol 39(1):98-106 (2016).

Post-translational Modification

Ubiquitinated at Lys-233 by the SCF(FBXO38) complex, leading to its proteasomal degradation. Ubiquitinated via 'Lys-48'-linked polyubiquitin chains.; Tyrosine phosphorylated at Tyr-223 (within ITIM motif) and Tyr-248 (ITSM motif) upon ligand binding. Phosphorylation at Tyr-248 promotes the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta.; N-glycosylation at Asn-58 consists of two N-acetylglucosamine units and one fucose. N-glycosylation does not affect binding to nivolumab drug.

Subcellular Location

Membrane.

UNIPROT

SwissProt: Q15116 Human

Synonyms