Immune checkpoint: Difference between revisions
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[[Monoclonal antibody|Monoclonal antibodies]] have been developed to target immune checkpoints. | [[Monoclonal antibody|Monoclonal antibodies]] have been developed to target immune checkpoints. | ||
Drug toxicities include<ref name="pmid27809739">{{cite journal| author=Bourke JM, O'Sullivan M, Khattak MA| title=Management of adverse events related to new cancer immunotherapy (immune checkpoint inhibitors). | journal=Med J Aust | year= 2016 | volume= 205 | issue= 9 | pages= 418-424 | pmid=27809739 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27809739 }} </ref>: | Drug toxicities include<ref name="pmid27809739">{{cite journal| author=Bourke JM, O'Sullivan M, Khattak MA| title=Management of adverse events related to new cancer immunotherapy (immune checkpoint inhibitors). | journal=Med J Aust | year= 2016 | volume= 205 | issue= 9 | pages= 418-424 | pmid=27809739 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27809739 }} </ref><ref name="pmid28973656">{{cite journal| author=Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE et al.| title=Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. | journal=JAMA Oncol | year= 2017 | volume= | issue= | pages= | pmid=28973656 | doi=10.1001/jamaoncol.2017.3064 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28973656 }} </ref>: | ||
* Gastrointestinal | * Gastrointestinal | ||
* Dermatologic | * Dermatologic | ||
Revision as of 04:03, 26 November 2017
Immune checkpoint inhibitors
Monoclonal antibodies have been developed to target immune checkpoints.
Drug toxicities include[1][2]:
- Gastrointestinal
- Dermatologic
- Endocrine
- Exacerbation of pre-existing autoimmune disease.
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."[3][4]
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”. [5]
Nivolumab may case drug toxicity in about 40% of patients - rash and diarrhea are the most common effects[6].
Examples:
- Pembrolizumab (Keytruda)
- Nivolumab (Opdivo)
PD-L1 inhibitors
- Atezolizumab (Tecentriq)
- Avelumab (Bavencio)
- Durvalumab (Imfinzi)
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."[7]
Ipilimumab may cause autoimmune pituitary disease[8] and exacerbate autoimmune disease in recipients with pre-existing autoimmune disease[9].
Examples:
- Ipilimumab (Yervoy)
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."[10]
Examples:
See also
References
- ↑ 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.
- ↑ 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. doi:10.1001/jamaoncol.2017.3064. PMID 28973656.
- ↑ Anonymous (2024), Programmed Cell Death 1 Receptor (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Boussiotis VA (2016). "Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway". N Engl J Med. 375 (18): 1767–1778. doi:10.1056/NEJMra1514296. PMC 5575761. PMID 27806234.
- ↑ 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. doi:10.1056/NEJMp1709968. PMID 29020592.
- ↑ 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. doi:10.1056/NEJMoa1200690. PMC 3544539. PMID 22658127.
- ↑ Anonymous (2024), CTLA-4 Antigen (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ 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. doi:10.1210/jc.2012-4075. PMID 23471977.
- ↑ 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. doi:10.1001/jamaoncol.2015.4368. PMID 26633184.
- ↑ Template:Mesh