Anti-PD-1 antibodies

use, action, side effects

Abstract

Programmed cell death protein 1 (PD-1) is a transmembrane protein expressed in T, B, NK cells, monocytes, and dendritic cells. The binding of PD-1 to its ligands inhibits tumor cell apoptosis, stimulates T-cell depletion, and prevents active antitumor response, which consequently enables an uninhibited growth and development of tumor cells.
PD-1 receptor inhibitors pembrolizumab and nivolumab are already used in the treatment of various types of advanced cancer, such as melanoma, non-small cell lung cancer, Hodgkin’s lymphoma, and renal carcinoma. Depending on the indication and line of treatment, a different number of patients responds to the treatment successfully, ranging from 18 % to 80 % of patients. The particularities of treatment with immunotherapy include very long-lasting remissions and, in individual patients, we might even dare talk about cure.
The most common side effects are fatigue, pruritus, rash, diarrhea, and nausea. Among the most serious side effects are immune-related adverse reactions – including colitis, thyroiditis, pneumonitis, hepatitis, and nephritis – and severe infusion-related reactions.

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Povzetek

Protein programirane celične smrti 1:PD-1 (Programmed cell death protein 1) je transmembranski protein, ki je izražen na celicah T, B, NK ter monocitih in dendritičnih celicah. Vezava med PD-1 in njegovimi ligandi zavira tumorsko celično apoptozo, spodbuja izčrpanost T-celic in preprečuje aktiven antitumorski odziv, kar posledično omogoča nemoteno rast in razvoj tumorskih celic.
Zaviralca receptorja PD-1, pembrolizumab in nivolumab, že uporabljamo v zdravljenju različnih vrst napredovalega raka, kot so: melanom, nedrobnocelični karcinom pljuč, Hodgkinov limfom in karcinom ledvic. Na zdravljenje odgovori zelo različno število bolnikov, kar je odvisno od indikacije in linije zdravljenja, to je od pri 18 do 80 odstotkih bolnikov. Posebnosti zdravljenja z imunoterapijo so zelo dolgotrajne remisije, pri posameznih bolnikih pa bomo morebiti upali govoriti celo o ozdravitvi.
Najpogostejši neželeni učinki so utrujenost, srbečica, izpuščaji, driska in slabost. Najresnejši neželeni učinki so imunsko pogojeni neželeni učinki in hude z infuzijo povezane reakcije. Imunsko pogojeni neželeni učinki so kolitis, tiroiditis, pneumonitis, hepatitis in nefritis.