Programmed cell death 1

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Programmed cell death 1, abbreviated PDCD1 and PD1,[1] is a protein (and gene) with an important role in immune system regulation and cancer. It is found on T lymphocytes.

It is also known as CD279.

PD1 binds with programmed death-ligand 1 (dealt with separately) and programmed death-ligand 2.[2]

Background

Cytotoxic T cell function is regulated by receptor pairs found on the tumour and lymphocyte:[2]

Function Tumour cell T cell
Antigen presentation MHC TCR
Signal inhibition PD-1 PD-L1 (CD274), PD-L2 (CD273)

Drugs

  • Pembrolizumab.
  • Nivolumab.
  • Atezolizumab.
  • Durvalumab.
  • Avelumab.

Uncertain whether it binds PD-1:

  • Pidilizumab.

IHC

  • There is no standard antibody.
  • Currently, each drug company has its own clone. Whether the antibodies are interchangeable is a subject of study.
Clone IHC platform Associated drug Testing required
28-8 Dako Nivolumab[3] no testing for squamous carcinoma, pending further information for non-squamous
22C3 Dako Pembrolizumab[4] testing required
SP142 Ventana Atezolizumab[5] testing required
SP263 Ventana Durvalumab testing likely required

See also

References

  1. Online 'Mendelian Inheritance in Man' (OMIM) 600244
  2. 2.0 2.1 Ribas, A. (Jun 2012). "Tumor immunotherapy directed at PD-1.". N Engl J Med 366 (26): 2517-9. doi:10.1056/NEJMe1205943. PMID 22658126.
  3. Borghaei, H.; Paz-Ares, L.; Horn, L.; Spigel, DR.; Steins, M.; Ready, NE.; Chow, LQ.; Vokes, EE. et al. (Oct 2015). "Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.". N Engl J Med 373 (17): 1627-39. doi:10.1056/NEJMoa1507643. PMID 26412456.
  4. Garon, EB.; Rizvi, NA.; Hui, R.; Leighl, N.; Balmanoukian, AS.; Eder, JP.; Patnaik, A.; Aggarwal, C. et al. (May 2015). "Pembrolizumab for the treatment of non-small-cell lung cancer.". N Engl J Med 372 (21): 2018-28. doi:10.1056/NEJMoa1501824. PMID 25891174.
  5. Fehrenbacher, L.; Spira, A.; Ballinger, M.; Kowanetz, M.; Vansteenkiste, J.; Mazieres, J.; Park, K.; Smith, D. et al. (Apr 2016). "Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial.". Lancet 387 (10030): 1837-46. doi:10.1016/S0140-6736(16)00587-0. PMID 26970723.