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TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL

The therapeutic potential of targeting CD19 in B cell malignancies has garnered attention in the past decade, resulting in the introduction of novel immunotherapy agents. Encouraging clinical data have been reported for T cell-based targeting agents, such as anti-CD19/CD3 bispecific T-cell engager b...

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Autores principales: Malik-Chaudhry, Harbani K., Prabhakar, Kirthana, Ugamraj, Harshad S., Boudreau, Andrew A., Buelow, Benjamin, Dang, Kevin, Davison, Laura M., Harris, Katherine E., Jorgensen, Brett, Ogana, Heather, Pham, Duy, Schellenberger, Ute, Van Schooten, Wim, Buelow, Roland, Iyer, Suhasini, Trinklein, Nathan D., Rangaswamy, Udaya S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023237/
https://www.ncbi.nlm.nih.gov/pubmed/33818299
http://dx.doi.org/10.1080/19420862.2021.1890411
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author Malik-Chaudhry, Harbani K.
Prabhakar, Kirthana
Ugamraj, Harshad S.
Boudreau, Andrew A.
Buelow, Benjamin
Dang, Kevin
Davison, Laura M.
Harris, Katherine E.
Jorgensen, Brett
Ogana, Heather
Pham, Duy
Schellenberger, Ute
Van Schooten, Wim
Buelow, Roland
Iyer, Suhasini
Trinklein, Nathan D.
Rangaswamy, Udaya S.
author_facet Malik-Chaudhry, Harbani K.
Prabhakar, Kirthana
Ugamraj, Harshad S.
Boudreau, Andrew A.
Buelow, Benjamin
Dang, Kevin
Davison, Laura M.
Harris, Katherine E.
Jorgensen, Brett
Ogana, Heather
Pham, Duy
Schellenberger, Ute
Van Schooten, Wim
Buelow, Roland
Iyer, Suhasini
Trinklein, Nathan D.
Rangaswamy, Udaya S.
author_sort Malik-Chaudhry, Harbani K.
collection PubMed
description The therapeutic potential of targeting CD19 in B cell malignancies has garnered attention in the past decade, resulting in the introduction of novel immunotherapy agents. Encouraging clinical data have been reported for T cell-based targeting agents, such as anti-CD19/CD3 bispecific T-cell engager blinatumomab and chimeric antigen receptor (CAR)-T therapies, for acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma (B-NHL). However, clinical use of both blinatumomab and CAR-T therapies has been limited due to unfavorable pharmacokinetics (PK), significant toxicity associated with cytokine release syndrome and neurotoxicity, and manufacturing challenges. We present here a fully human CD19xCD3 bispecific antibody (TNB-486) for the treatment of B-NHL that could address the limitations of the current approved treatments. In the presence of CD19+ target cells and T cells, TNB-486 induces tumor cell lysis with minimal cytokine release, when compared to a positive control. In vivo, TNB-486 clears CD19+ tumor cells in immunocompromised mice in the presence of human peripheral blood mononuclear cells in multiple models. Additionally, the PK of TNB-486 in mice or cynomolgus monkeys is similar to conventional antibodies. This new T cell engaging bispecific antibody targeting CD19 represents a novel therapeutic that induces potent T cell-mediated tumor-cell cytotoxicity uncoupled from high levels of cytokine release, making it an attractive candidate for B-NHL therapy.
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spelling pubmed-80232372021-04-15 TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL Malik-Chaudhry, Harbani K. Prabhakar, Kirthana Ugamraj, Harshad S. Boudreau, Andrew A. Buelow, Benjamin Dang, Kevin Davison, Laura M. Harris, Katherine E. Jorgensen, Brett Ogana, Heather Pham, Duy Schellenberger, Ute Van Schooten, Wim Buelow, Roland Iyer, Suhasini Trinklein, Nathan D. Rangaswamy, Udaya S. MAbs Report The therapeutic potential of targeting CD19 in B cell malignancies has garnered attention in the past decade, resulting in the introduction of novel immunotherapy agents. Encouraging clinical data have been reported for T cell-based targeting agents, such as anti-CD19/CD3 bispecific T-cell engager blinatumomab and chimeric antigen receptor (CAR)-T therapies, for acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma (B-NHL). However, clinical use of both blinatumomab and CAR-T therapies has been limited due to unfavorable pharmacokinetics (PK), significant toxicity associated with cytokine release syndrome and neurotoxicity, and manufacturing challenges. We present here a fully human CD19xCD3 bispecific antibody (TNB-486) for the treatment of B-NHL that could address the limitations of the current approved treatments. In the presence of CD19+ target cells and T cells, TNB-486 induces tumor cell lysis with minimal cytokine release, when compared to a positive control. In vivo, TNB-486 clears CD19+ tumor cells in immunocompromised mice in the presence of human peripheral blood mononuclear cells in multiple models. Additionally, the PK of TNB-486 in mice or cynomolgus monkeys is similar to conventional antibodies. This new T cell engaging bispecific antibody targeting CD19 represents a novel therapeutic that induces potent T cell-mediated tumor-cell cytotoxicity uncoupled from high levels of cytokine release, making it an attractive candidate for B-NHL therapy. Taylor & Francis 2021-04-04 /pmc/articles/PMC8023237/ /pubmed/33818299 http://dx.doi.org/10.1080/19420862.2021.1890411 Text en © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Report
Malik-Chaudhry, Harbani K.
Prabhakar, Kirthana
Ugamraj, Harshad S.
Boudreau, Andrew A.
Buelow, Benjamin
Dang, Kevin
Davison, Laura M.
Harris, Katherine E.
Jorgensen, Brett
Ogana, Heather
Pham, Duy
Schellenberger, Ute
Van Schooten, Wim
Buelow, Roland
Iyer, Suhasini
Trinklein, Nathan D.
Rangaswamy, Udaya S.
TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL
title TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL
title_full TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL
title_fullStr TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL
title_full_unstemmed TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL
title_short TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL
title_sort tnb-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of b-nhl
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023237/
https://www.ncbi.nlm.nih.gov/pubmed/33818299
http://dx.doi.org/10.1080/19420862.2021.1890411
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