Pd-1 antibody
Synonym(s)
DefinitionThis section has been translated automatically.
PD-1 = Acronym for Programmed Cell Death 1 Protein. Anti-PD-1 antibodies block the interaction between programmed cell death and its ligand PDL1. Programmed cell death (PD-1) is an important receptor protein that is expressed by activated T cells. PD-1 functions primarily in tissue where T cells encounter the immunosuppressive ligand of PD-1. These PD-1 ligands (PD-L1 and PD-L2) are produced by tumour cells themselves as well as by cells of the tumour stroma. If the interactions between PD-1 and its ligands are inhibited, the effectiveness of the ligands is reduced. Their immunosuppressive effect is weakened. The T-cell response (e.g. against the tumour tissue) is strengthened, an immunosuppressive response is suppressed.
Pharmacodynamics (Effect)This section has been translated automatically.
Analogous to the effect of ipilimumab, anti-PD1/PDL1 antibodies thus enable the patient's immune system to attack the tumor itself.
In a study published in July 2014 in the New England Journal of Medicine, 38 percent of 135 patients with advanced melanoma responded to therapy with the anti-PD1 antibody. It was irrelevant whether the patients had previously received ipilimumab(CTLA-4-Ak).
Prior studies in patients with advanced melanoma (n = 104), non-small cell lung cancer (n = 122), renal cell carcinoma (n = 34), and prostate carcinoma (n = 17) and colon carcinoma (n = 19) were included. The anti-PD-1 antibody was applied every 2 weeks. Patients received a maximum of 12 treatment cycles until disease progression or complete remission. Patients with squamous cell carcinoma had the best response rate (33%). 26 of 94 evaluable melanoma patients (28%) showed an objectifiable response.
Undesirable effectsThis section has been translated automatically.
The most common ADRs were fatigue, poor appetite, nausea, diarrhea, cough, dyspnea, constipation, vomiting, exanthema, fever, and headache. Forty-one of the 296 patients had 3rd- and 4th-degree UAW events. 15 patients discontinued treatment because of UAW . 3 deaths related to the study medication were observed (pneumonitis).
Furthermore, maculopapular, psoriasiform, lichenoid, and in rarer cases autoimmune bullous exanthema (see below Lichen ruber pemphigoides) and vitiligo were reported (Mueller KA et al. 2021).
PreparationsThis section has been translated automatically.
Pembrolizumab (MK-3475 / MSD); nivolumab; cemiplimab (approved by EMA for SCC since 2019)
Note(s)This section has been translated automatically.
Conclusion: Anti-PD-L1 antibody induces objective response in patients with non-small cell lung cancer, melanoma or renal car cinoma.
LiteratureThis section has been translated automatically.
- Blank C et al (2004) PD-L1 / B7H-1 inhibits the effector phase of tumor rejection by T-cell receptor (TCR) transgenic CD8 + T-cells. Cancer Res 64: 1140-1145
- Mohr P (2014) Immunoncological therapy with ipilimumab-innovative approach heralds a new era in cancer therapy Thieme Case Report 4:1-24
- Ribas A et al (2004) J Clin Oncol 32: Abstr. LBA9000
- Topalian SL et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366: 2443-2454