A Novel Class of On-Treatment Cancer Immunotherapy Biomarker: Trough Levels of Antibody Therapeutics in Peripheral Blood

ABSTRACT

While immune checkpoint blockade has revolutionized cancer treatment, unfortunately most patients do not benefit from this treatment. Many pharmacodynamic (PD) studies have revealed essential requirements for successful cancer immunotherapy that may provide insight into how we can improve these agents. Despite enormous efforts focused on interrogating the immune system using different biospecimens (e.g. blood, primary tumor, metastatic tumor, microbiome samples), a variety of technologies (e.g. flow cytometry, bulk and single-cell RNA-sequencing, immunohistochemistry), and wide-ranging disciplines (e.g. pathology, genomics, bioinformatics, immunology, cancer biology, metabolomics, bacteriology), discovery of consistent biomarkers of response have remained elusive. Pharmacokinetics (PK) studies, however, not only provide critical information regarding safe dosing but may also reveal useful biomarkers. For example, recent studies found that trough levels of therapeutic monoclonal antibodies (mAbs) or clearance (CL) of them were associated with clinical outcome, which suggests that trough levels of mAbs may represent a new class of on-treatment cancer immunotherapy biomarker. In this review, we summarize the potential utility of trough levels of mAbs, the mechanism of varying PK, consideration for therapeutic drug monitoring, and assay attributes that will facilitate wider utilization of PK information in conjunction with PD assessments.

KEYWORDS:

• Antibody therapeutics
• biomarkers
• cancer immunotherapy
• clearance
• immune checkpoint blockade
• inflammation
• pharmacodynamics
• pharmacokinetics
• trough levels

Disclosure statement

YK: research support from Bristol Myers Squibb (BMS), GlaxoSmithKline, and Shimadzu. WLR: research support from BMS, GlaxoSmithKline, MiNA Therapeutics, Inhibrx, Veana Therapeutics, Shimadzu, OncoSec, Galecto, Canwell Pharma, Turn Bio, and Calibr; patents/licensing fees: Galectin Therapeutics; advisory boards: Medicenna, Vesselon, and Veana Therapeutics.

Additional information

Funding

The work was supported by the Shimadzu Providence Portland Medical Foundation .