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Clinical translation of antibody drug conjugate dosing in solid tumors from preclinical mouse data.
- Source :
-
Science advances [Sci Adv] 2024 May 31; Vol. 10 (22), pp. eadk1894. Date of Electronic Publication: 2024 May 31. - Publication Year :
- 2024
-
Abstract
- Antibody drug conjugates (ADCs) have made impressive strides in the clinic in recent years with 11 Food and Drug Administration approvals, including 6 for the treatment of patients with solid tumors. Despite this success, the development of new agents remains challenging with a high failure rate in the clinic. Here, we show that current approved ADCs for the treatment of patients with solid tumors can all show substantial efficacy in some mouse models when administered at a similar weight-based [milligrams per kilogram (mg/kg)] dosing in mice that is tolerated in the clinic. Mechanistically, equivalent mg/kg dosing results in a similar drug concentration in the tumor and a similar tissue penetration into the tumor due to the unique delivery features of ADCs. Combined with computational approaches, which can account for the complex distribution within the tumor microenvironment, these scaling concepts may aid in the evaluation of new agents and help design therapeutics with maximum clinical efficacy.
- Subjects :
- Animals
Mice
Humans
Xenograft Model Antitumor Assays
Translational Research, Biomedical
Disease Models, Animal
Tumor Microenvironment drug effects
Cell Line, Tumor
Antineoplastic Agents administration & dosage
Antineoplastic Agents pharmacokinetics
Drug Evaluation, Preclinical
Immunoconjugates administration & dosage
Immunoconjugates pharmacokinetics
Immunoconjugates pharmacology
Neoplasms drug therapy
Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2375-2548
- Volume :
- 10
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Science advances
- Publication Type :
- Academic Journal
- Accession number :
- 38820153
- Full Text :
- https://doi.org/10.1126/sciadv.adk1894