Antibody List, N - Z Antibodies

PD-L1

PD-1 (programmed cell death-1) is a receptor on the T-cell, which when binding to PD-L1 or PD-L2 can result in inhibition of the cytotoxic T-cell response.  

This is a mechanism for tumors (by expressing PD-L1 and/or PD-L2) to escape the immune recognition of these cytotoxic T-cells, via inhibition of T-cell activation.  Some tumors with over expression of PD-L1 have been shown to be more aggressive, which is thought to be secondary suppression of the immune system via PD-L1 expression.  Inhibitors of PD-L1 is a fast developing and quickly changing area with investigating occurring in almost all tumor types.  It is important to be up to date on current research status and standard or care with regards to when to test, and what antibody to use.  Some may be part of FDA approved testing kits, and close communication with the testing/reference lab is important for correct and timely testing.
Multiple PD-L1 and PD-L2 inhibitors are under investigation. 
  • In the fall of 2015, FDA approval was given to pembrolizumab (Keytruda, Merck) for the treatment of metastatic non-small cell lung carcinoma (NSCLC) whose tumors express PD-L1 (clone 22C3, Dako) in >50% of the tumor cells and have progressed after platinum based chemotherapy or tumors treated with inhibitors to EGFR and ALK.  Pembrolizumab has also been approved for the treatment of un-resectable/metastatic melanoma (no known IHC PD-L1 testing requirement for drug administration).
  • Nivolumab (OPDIVO™) has been approved by the FDA for patients with previous treated NSCLC.  There is also FDA approval for the DAKO PD-L1 IHC 28-8 pharmDx(TM) immunohistomchemistry staining kit, which uses clone 28-8.  Patients with expression ≥1% saw significant improvement in survival (most improvement was seen with expression ≥5% and ≥10%.
  • Durvalumab (IMFINIZI™) produced by Astrazeneca has FDA approval for use in urothelial carcinoma (under certain circumstances), and is also under clinical investigation in the areas of NSCLC, head and neck squamous cell carcinoma (SCC), and other malignancies.
    • Expression can be determined in the setting of urothelial carcinoma (although not required) with the Ventana® PD-L1 (SP263) assay.
      • PD-L1 High Expressors:
        • ≥25% expression on tumor cells
        • If immune cells are >1% of the tumor area and ≥25% PD-L1 expression on immune cells
        • If immune cells are ≤1% of the tumor area, and 100% expression on immune cells

 

By blocking the ligand PD-L1, the monoclonal antibody drug inhibits the suppressive effect on cytotoxic T-cells through the PD-1 receptor on the cytotoxic T-cell, and therefore allow a cytotoxic T-cell response against the tumor.
 
Other drugs, including nivolumab (does not require IHC staining for PD-1) have also been approved for metastatic lung squamous cell carcinoma.
 
Drugs targeting the PD-1 inhibition of cytotoxic T-cells is a very active area of research for multiple neoplastic conditions.  Review of the most current data is the medical literature is important to knowing indications and proper testing for a particular patient. 
References
Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372: 2018–2028. doi:10.1056/NEJMoa1501824
 
Cagle PT, Bernicker EH.  A New Immunotherapy Drug Creates a Watershed for the Surgical Pathologist’s Role in Patient Care.  Arch Pathol Lab Med. 2015;139: 1329-1340.