Cancer immunotherapy-related adverse events : causes and challenges

Despite the success and ongoing promise of monoclonal antibody-targeted immune checkpoint inhibitor immunotherapy of advanced malignancies, in particular, antibodies directed against CTLA-4 and PD-1/PD-L1, the development of immune-related adverse events (irAEs) remains a constraint of this type of therapy. Although rarely fatal, the occurrence of irAEs may necessitate discontinuation of immunotherapy, as well as administration of corticosteroids or other immunosuppressive therapies that may not only compromise efficacy but also predispose for development of opportunistic infection. Clearly, retention of efficacy of immune checkpoint-targeted therapies with concurrent attenuation of immune-mediated toxicity represents a formidable challenge. In this context, the current brief review examines mechanistic relationships between these events, as well as recent insights into immunopathogenesis, and strategies which may contribute to resolving this issue. These sections are preceded by brief overviews of the discovery and functions of CTLA-4 and PD-1, as well as the chronology of the development of immunotherapeutic monoclonal antibodies which target these immune checkpoint inhibitors.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:28

Enthalten in:

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer - 28(2020), 12 vom: 28. Dez., Seite 6111-6117

Sprache:

Englisch

Beteiligte Personen:

Blidner, Ada G [VerfasserIn]
Choi, Jennifer [VerfasserIn]
Cooksley, Tim [VerfasserIn]
Dougan, Michael [VerfasserIn]
Glezerman, Ilya [VerfasserIn]
Ginex, Pamela [VerfasserIn]
Girotra, Monica [VerfasserIn]
Gupta, Dipti [VerfasserIn]
Johnson, Douglas [VerfasserIn]
Shannon, Vickie R [VerfasserIn]
Suarez-Almazor, Maria [VerfasserIn]
Rapoport, Bernardo L [VerfasserIn]
Anderson, Ronald [VerfasserIn]

Links:

Volltext

Themen:

Antibodies, Monoclonal
Antineoplastic Agents, Immunological
B7-H1 Antigen
CD274 protein, human
CTLA-4 Antigen
CTLA4 protein, human
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
Immune Checkpoint Inhibitors
Immunologic Factors
Ipilimumab
Journal Article
Microbiome
Nivolumab
PDCD1 protein, human
Programmed Cell Death 1 Receptor
Programmed cell death protein 1 (PD-1)
Regulatory T lymphocytes (Tregs)
Review

Anmerkungen:

Date Completed 20.01.2021

Date Revised 12.10.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s00520-020-05705-5

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM314304231