Difference between revisions of "Programmed cell death 1"

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*Avelumab.
*Avelumab.


Uncertain whether it binds PD-L1:
Uncertain whether it binds PD-1:
*Pidilizumab.
*Pidilizumab.


==IHC==
==IHC==
*There is no standard PD-1 antibody; each drug company has its own clone.
*There is no standard antibody.
 
*Currently, each drug company has its own clone. Whether the antibodies are interchangeable is a subject of study.
*Nivolumab: PD-L1 28-8: provides prognostic inflammation, may benefit without staining.<ref>{{Cite journal  | last1 = Borghaei | first1 = H. | last2 = Paz-Ares | first2 = L. | last3 = Horn | first3 = L. | last4 = Spigel | first4 = DR. | last5 = Steins | first5 = M. | last6 = Ready | first6 = NE. | last7 = Chow | first7 = LQ. | last8 = Vokes | first8 = EE. | last9 = Felip | first9 = E. | title = Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. | journal = N Engl J Med | volume = 373 | issue = 17 | pages = 1627-39 | month = Oct | year = 2015 | doi = 10.1056/NEJMoa1507643 | PMID = 26412456 }}</ref> no for squamous, ? non-squamous
<center>
*Pembrolizumab: PD-L1 22C3:<ref>{{Cite journal  | last1 = Garon | first1 = EB. | last2 = Rizvi | first2 = NA. | last3 = Hui | first3 = R. | last4 = Leighl | first4 = N. | last5 = Balmanoukian | first5 = AS. | last6 = Eder | first6 = JP. | last7 = Patnaik | first7 = A. | last8 = Aggarwal | first8 = C. | last9 = Gubens | first9 = M. | title = Pembrolizumab for the treatment of non-small-cell lung cancer. | journal = N Engl J Med | volume = 372 | issue = 21 | pages = 2018-28 | month = May | year = 2015 | doi = 10.1056/NEJMoa1501824 | PMID = 25891174 }}</ref> IHC testing necessary to use in USA.
{| class="wikitable sortable"
 
!Clone
*Atezolizumab <ref name=pmid26970723>{{Cite journal  | last1 = Fehrenbacher | first1 = L. | last2 = Spira | first2 = A. | last3 = Ballinger | first3 = M. | last4 = Kowanetz | first4 = M. | last5 = Vansteenkiste | first5 = J. | last6 = Mazieres | first6 = J. | last7 = Park | first7 = K. | last8 = Smith | first8 = D. | last9 = Artal-Cortes | first9 = A. | title = Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. | journal = Lancet | volume = 387 | issue = 10030 | pages = 1837-46 | month = Apr | year = 2016 | doi = 10.1016/S0140-6736(16)00587-0 | PMID = 26970723 }}</ref> - testing required.
!IHC platform
 
!Associated drug
*Durvalumab: testing required.
!Testing required
|-
| 28-8
| Dako
| Nivolumab<ref>{{Cite journal  | last1 = Borghaei | first1 = H. | last2 = Paz-Ares | first2 = L. | last3 = Horn | first3 = L. | last4 = Spigel | first4 = DR. | last5 = Steins | first5 = M. | last6 = Ready | first6 = NE. | last7 = Chow | first7 = LQ. | last8 = Vokes | first8 = EE. | last9 = Felip | first9 = E. | title = Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. | journal = N Engl J Med | volume = 373 | issue = 17 | pages = 1627-39 | month = Oct | year = 2015 | doi = 10.1056/NEJMoa1507643 | PMID = 26412456 }}</ref>
| no testing for squamous carcinoma, pending further information for non-squamous
|-
| 22C3
| Dako
| Pembrolizumab<ref>{{Cite journal  | last1 = Garon | first1 = EB. | last2 = Rizvi | first2 = NA. | last3 = Hui | first3 = R. | last4 = Leighl | first4 = N. | last5 = Balmanoukian | first5 = AS. | last6 = Eder | first6 = JP. | last7 = Patnaik | first7 = A. | last8 = Aggarwal | first8 = C. | last9 = Gubens | first9 = M. | title = Pembrolizumab for the treatment of non-small-cell lung cancer. | journal = N Engl J Med | volume = 372 | issue = 21 | pages = 2018-28 | month = May | year = 2015 | doi = 10.1056/NEJMoa1501824 | PMID = 25891174 }}</ref>  
| testing required
|-
| SP142
| Ventana
| Atezolizumab<ref name=pmid26970723>{{Cite journal  | last1 = Fehrenbacher | first1 = L. | last2 = Spira | first2 = A. | last3 = Ballinger | first3 = M. | last4 = Kowanetz | first4 = M. | last5 = Vansteenkiste | first5 = J. | last6 = Mazieres | first6 = J. | last7 = Park | first7 = K. | last8 = Smith | first8 = D. | last9 = Artal-Cortes | first9 = A. | title = Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. | journal = Lancet | volume = 387 | issue = 10030 | pages = 1837-46 | month = Apr | year = 2016 | doi = 10.1016/S0140-6736(16)00587-0 | PMID = 26970723 }}</ref>
| testing required
|-
| SP263
| Ventana
| Durvalumab
| testing likely required
|}
</center>


==See also==
==See also==

Latest revision as of 17:51, 23 November 2016

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.
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