Immune checkpoint-targeted antibodies: a room for dose and schedule optimization?

J Hematol Oncol. 2022 Jan 15;15(1):6. doi: 10.1186/s13045-021-01182-3.

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.

Keywords: Dosing interval; Immunotherapy; Oncology; Pharmacokinetics; Therapeutic antibodies.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Dose-Response Relationship, Drug
  • Drug Monitoring
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / pharmacokinetics
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Maximum Tolerated Dose
  • Neoplasms / drug therapy*
  • Neoplasms / immunology

Substances

  • Immune Checkpoint Inhibitors