Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation

Abstract : Potentiation of hostile monoclonal antibodies (mAb) by chemotherapeutic agents constitutes a valuable strategy for designing effective and safer therapy against cancer. Here we provide a protocol to identify a rational combination at the preclinical step. First, we describe a cell-based assay to assess the synergism between anticancer mAb and cytotoxic drugs, that uses the combination index equation of Chou and Talalay 1. This includes the measurement of tumor cell drug-and antibody-sensitivity using an MTT assay, followed by an automated computer analysis to calculate the combination index (CI) values. CI values of <1 indicate synergism between tested mAbs and cytotoxic agents 1. To corroborate the in vitro findings in vivo, we further describe a method to assess the combination regimen efficacy in a xenograft tumor model. In this model, the combined regimen significantly delays tumor growth, which results in a significant extended survival in comparison to single-agent controls. Importantly, the in vivo experimentation reveals that the combination regimen is well tolerated. This protocol allows the effective evaluation of anticancer drug combinations in preclinical models and the identification of rational combination to evaluate in clinical trials.
Document type :
Journal articles
Complete list of metadatas

Cited literature [30 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01958827
Contributor : Elizabeth Bernardo <>
Submitted on : Tuesday, December 18, 2018 - 11:42:10 AM
Last modification on : Monday, May 20, 2019 - 3:32:02 PM
Long-term archiving on : Wednesday, March 20, 2019 - 2:50:46 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Meriem Bahri, Julien Fleurence, Sébastien Faraj, Mohamed Ben Mostefa Daho, Sophie Fougeray, et al.. Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation. Journal of visualized experiments : JoVE, JoVE, 2018, e58291, epub ahead of print. ⟨10.3791/58291⟩. ⟨inserm-01958827⟩

Share

Metrics

Record views

67