Immune checkpoint-targeted antibodies: a room for dose and schedule optimization?
Abstract Anti-CTLA-4 and anti-PD-1/PD-L1 immune checkpoint inhibitors are therapeutic monoclonal antibodies that do not target cancer cells but are designed to reactivate or promote antitumor immunity. Dosing and scheduling of these biologics were established according to conventional drug developme...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13045-021-01182-3 |
| _version_ | 1798026215583383552 |
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| author | Christophe Maritaz Sophie Broutin Nathalie Chaput Aurélien Marabelle Angelo Paci |
| author_facet | Christophe Maritaz Sophie Broutin Nathalie Chaput Aurélien Marabelle Angelo Paci |
| author_sort | Christophe Maritaz |
| collection | DOAJ |
| description | Abstract Anti-CTLA-4 and anti-PD-1/PD-L1 immune checkpoint inhibitors are therapeutic monoclonal antibodies that do not target cancer cells but are designed to reactivate or promote antitumor immunity. Dosing and scheduling of these biologics were established according to conventional drug development models, even though the determination of a maximum tolerated dose in the clinic could only be defined for anti-CTLA-4. Given the pharmacology of these monoclonal antibodies, their high interpatient pharmacokinetic variability, the actual clinical benefit as monotherapy that is observed only in a specific subset of patients, and the substantial cost of these treatments, a number of questions arise regarding the selected dose and the dosing interval. This review aims to outline the development of these immunotherapies and considers optimization options that could be used in clinical practice. |
| first_indexed | 2024-04-11T18:31:43Z |
| format | Article |
| id | doaj.art-2613f391c3aa4591b4f5a94f5bbaf65c |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-11T18:31:43Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-2613f391c3aa4591b4f5a94f5bbaf65c2022-12-22T04:09:25ZengBMCJournal of Hematology & Oncology1756-87222022-01-0115111610.1186/s13045-021-01182-3Immune checkpoint-targeted antibodies: a room for dose and schedule optimization?Christophe Maritaz0Sophie Broutin1Nathalie Chaput2Aurélien Marabelle3Angelo Paci4Pharmacology Department, U1030 INSERM, University Paris-Saclay, Gustave Roussy Cancer CampusPharmacology Department, U1030 INSERM, University Paris-Saclay, Gustave Roussy Cancer CampusLaboratory for Immunomonitoring in Oncology (LIO), Faculty of Pharmacy, University Paris-Saclay, Gustave Roussy Cancer CampusDrug Development Unit (DITEP), LRTI U1015 INSERM, Gustave RoussyPharmacology Department, U1030 INSERM, University Paris-Saclay, Gustave Roussy Cancer CampusAbstract Anti-CTLA-4 and anti-PD-1/PD-L1 immune checkpoint inhibitors are therapeutic monoclonal antibodies that do not target cancer cells but are designed to reactivate or promote antitumor immunity. Dosing and scheduling of these biologics were established according to conventional drug development models, even though the determination of a maximum tolerated dose in the clinic could only be defined for anti-CTLA-4. Given the pharmacology of these monoclonal antibodies, their high interpatient pharmacokinetic variability, the actual clinical benefit as monotherapy that is observed only in a specific subset of patients, and the substantial cost of these treatments, a number of questions arise regarding the selected dose and the dosing interval. This review aims to outline the development of these immunotherapies and considers optimization options that could be used in clinical practice.https://doi.org/10.1186/s13045-021-01182-3ImmunotherapyTherapeutic antibodiesDosing intervalPharmacokineticsOncology |
| spellingShingle | Christophe Maritaz Sophie Broutin Nathalie Chaput Aurélien Marabelle Angelo Paci Immune checkpoint-targeted antibodies: a room for dose and schedule optimization? Journal of Hematology & Oncology Immunotherapy Therapeutic antibodies Dosing interval Pharmacokinetics Oncology |
| title | Immune checkpoint-targeted antibodies: a room for dose and schedule optimization? |
| title_full | Immune checkpoint-targeted antibodies: a room for dose and schedule optimization? |
| title_fullStr | Immune checkpoint-targeted antibodies: a room for dose and schedule optimization? |
| title_full_unstemmed | Immune checkpoint-targeted antibodies: a room for dose and schedule optimization? |
| title_short | Immune checkpoint-targeted antibodies: a room for dose and schedule optimization? |
| title_sort | immune checkpoint targeted antibodies a room for dose and schedule optimization |
| topic | Immunotherapy Therapeutic antibodies Dosing interval Pharmacokinetics Oncology |
| url | https://doi.org/10.1186/s13045-021-01182-3 |
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