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Diseases 2018, 6(2), 41; https://doi.org/10.3390/diseases6020041

Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review

Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
Received: 29 April 2018 / Revised: 17 May 2018 / Accepted: 18 May 2018 / Published: 19 May 2018
(This article belongs to the Special Issue Pediatric Diseases)
Full-Text   |   PDF [174 KB, uploaded 19 May 2018]

Abstract

Pediatric acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer diagnosis, with numbers rising gradually every year. This paper proposes a novel therapeutic agent for pediatric ALL on the basis of a failed clinical drug trial in 2006. TGN1412 was a promising therapeutic agent that yielded outstanding results in both in vitro studies and animal trials. It is a CD28 superagonist monoclonal antibody that activates T regulatory (TReg) cells in the absence of costimulation of the T cell receptor (TCR) by an antigen-presenting cell. This drug was intended as a solution to T cell deficient diseases such as B cell leukemia and autoimmune diseases such as rheumatoid arthritis. When phase I clinical trials were conducted, all volunteers that received the drug experienced severe cytokine release syndrome (CRS) and faced multiple-organ failure within hours. TGN1412 was reassessed and re-entered clinical trials as a therapeutic for rheumatoid arthritis. A new assay was developed to better quantify T cell response, and volunteers in this trial experienced no pro-inflammatory cytokine release. This essay analyzes how misinformation contributed to the failure of TGN1412 in clinical trials and how revisiting this therapeutic could yield a novel treatment for pediatric B cell leukemia. View Full-Text
Keywords: clinical trials; pediatric therapeutics; B cell leukemia clinical trials; pediatric therapeutics; B cell leukemia
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Brown, K.E. Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review. Diseases 2018, 6, 41.

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