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

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 agen...

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Detalles Bibliográficos
Autor principal: Brown, Katelyn E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023298/
https://www.ncbi.nlm.nih.gov/pubmed/29783736
http://dx.doi.org/10.3390/diseases6020041
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author Brown, Katelyn E.
author_facet Brown, Katelyn E.
author_sort Brown, Katelyn E.
collection PubMed
description 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 (T(Reg)) 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.
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spelling pubmed-60232982018-07-03 Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review Brown, Katelyn E. Diseases Review 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 (T(Reg)) 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. MDPI 2018-05-19 /pmc/articles/PMC6023298/ /pubmed/29783736 http://dx.doi.org/10.3390/diseases6020041 Text en © 2018 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Brown, Katelyn E.
Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review
title Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review
title_full Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review
title_fullStr Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review
title_full_unstemmed Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review
title_short Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review
title_sort revisiting cd28 superagonist tgn1412 as potential therapeutic for pediatric b cell leukemia: a review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023298/
https://www.ncbi.nlm.nih.gov/pubmed/29783736
http://dx.doi.org/10.3390/diseases6020041
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