Immune checkpoint

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Immune checkpoint inhibitors

Monoclonal antibodies are a type of cancer immunotherapy that have been developed to target immune checkpoints.

Drug toxicities include[1][2][3]:

  • Gastrointestinal
  • Dermatologic
  • Endocrine
  • Exacerbation of pre-existing autoimmune disease[4].

PD-1 inhibitors

These antibodies target the Programmed Cell Death 1 Receptor (PD-1 Receptor). Programmed Cell Death Type I is also known as apoptosis. The PD-1 Receptor is "an inhibitory T-lymphocyte receptor that has specificity for CD274 antigen and Programmed Cell Death 1 Ligand 2 Protein."[5][6]

Pembrolizumab was approved by the FDA for “patients with unresectable or metastatic, microsatellite-instability–high (MSI-H) or mismatch-repair–deficient (dMMR) solid tumors, regardless of tumor site or histology”. [7]

Nivolumab may case drug toxicity in about 40% of patients - rash and diarrhea are the most common effects[8].

Examples:

PD-L1 inhibitors

CTLA-4 blockade

The CTLA-4 Antigen is "an inhibitory T cell receptor that is closely related to CD28 antigen. It has specificity for CD80 antigen and CD86 antigen and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing peripheral tolerance."[9]

Ipilimumab may cause autoimmune pituitary disease[10] and exacerbate autoimmune disease in recipients with pre-existing autoimmune disease[11]. The U.S. FDA has issued guidance on managing side effects.[12][13]

Examples:

Raf protein kinase inhibitors

Raf inhibitors are "a family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF kinases. They are MAP kinase kinase kinases that play important roles in signal transduction."[14]

Examples:

See also

References

  1. Bourke JM, O'Sullivan M, Khattak MA (2016). "Management of adverse events related to new cancer immunotherapy (immune checkpoint inhibitors).". Med J Aust. 205 (9): 418–424. PMID 27809739. 
  2. Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE; et al. (2017). "Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis.". JAMA Oncol. PMID 28973656. doi:10.1001/jamaoncol.2017.3064. 
  3. Postow et al. http://www.nejm.org/doi/full/10.1056/NEJMra1703481 NEJM 2018
  4. Abdel-Wahab N, Shah M, Lopez-Olivo MA, Suarez-Almazor ME (2018). "Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease: A Systematic Review.". Ann Intern Med. PMID 29297009. doi:10.7326/M17-2073. 
  5. Anonymous (2018), Programmed Cell Death 1 Receptor (English). Medical Subject Headings. U.S. National Library of Medicine.
  6. Boussiotis VA (2016). "Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway.". N Engl J Med. 375 (18): 1767–1778. PMC 5575761Freely accessible. PMID 27806234. doi:10.1056/NEJMra1514296. 
  7. Lemery S, Keegan P, Pazdur R (2017). "First FDA Approval Agnostic of Cancer Site - When a Biomarker Defines the Indication.". N Engl J Med. 377 (15): 1409–1412. PMID 29020592. doi:10.1056/NEJMp1709968. 
  8. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF; et al. (2012). "Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.". N Engl J Med. 366 (26): 2443–54. PMC 3544539Freely accessible. PMID 22658127. doi:10.1056/NEJMoa1200690. 
  9. Anonymous (2018), CTLA-4 Antigen (English). Medical Subject Headings. U.S. National Library of Medicine.
  10. Corsello SM, Barnabei A, Marchetti P, De Vecchis L, Salvatori R, Torino F (2013). "Endocrine side effects induced by immune checkpoint inhibitors.". J Clin Endocrinol Metab. 98 (4): 1361–75. PMID 23471977. doi:10.1210/jc.2012-4075. 
  11. Johnson DB, Sullivan RJ, Ott PA, Carlino MS, Khushalani NI, Ye F; et al. (2016). "Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders.". JAMA Oncol. 2 (2): 234–40. PMID 26633184. doi:10.1001/jamaoncol.2015.4368. 
  12. https://www.fda.gov/downloads/Drugs/DrugSafety/PostMarketDrugsafetyInformationforPatientsandProviders/UCM249435.pdf
  13. https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=ipilimumab
  14. Template:Mesh

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