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Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas

CD19CAR T cells facilitate a transformational treatment in various relapsed and refractory aggressive B-lineage cancers. In general, encouraging response rates have been observed in B-lineage-derived non-Hodgkin’s lymphomas treated with CD19CAR T cells. The major cause of death in heavily pretreated...

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Autores principales: Atar, Daniel, Mast, Anna-Sophia, Scheuermann, Sophia, Ruoff, Lara, Seitz, Christian Martin, Schlegel, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599140/
https://www.ncbi.nlm.nih.gov/pubmed/36289682
http://dx.doi.org/10.3390/biomedicines10102420
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author Atar, Daniel
Mast, Anna-Sophia
Scheuermann, Sophia
Ruoff, Lara
Seitz, Christian Martin
Schlegel, Patrick
author_facet Atar, Daniel
Mast, Anna-Sophia
Scheuermann, Sophia
Ruoff, Lara
Seitz, Christian Martin
Schlegel, Patrick
author_sort Atar, Daniel
collection PubMed
description CD19CAR T cells facilitate a transformational treatment in various relapsed and refractory aggressive B-lineage cancers. In general, encouraging response rates have been observed in B-lineage-derived non-Hodgkin’s lymphomas treated with CD19CAR T cells. The major cause of death in heavily pretreated NHL patients is lymphoma progression and lymphoma recurrence. Inefficient CAR T cell therapy is the result of the limited potency of the CAR T cell product or is due to loss of the targeted antigen. Target antigen loss has been identified as the key factor that can be addressed stringently by dual- or multitargeted CAR T cell approaches. We have developed a versatile adapter CAR T cell technology (AdCAR) that allows multitargeting. Screening of three different B-lineage lymphoma cell lines has revealed distinct immune target profiles. Cancer-specific adapter molecule combinations may be utilized to prevent antigen immune escape. In general, CD19CAR T cells become non-functional in CD19 negative lymphoma subsets; however, AdCAR T cells can be redirected to alternative target antigens beyond CD19, such as CD20, CD22, CD79B, and ROR-1. The capability to flexibly shift CAR specificity by exchanging the adapter molecule’s specificity broadens the application and significantly increases the anti-leukemic and anti-lymphoma activity. The clinical evaluation of AdCAR T cells in lymphoma as a new concept of CAR T cell immunotherapy may overcome treatment failure due to antigen immune escape in monotargeted conventional CAR T cell therapies.
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spelling pubmed-95991402022-10-27 Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas Atar, Daniel Mast, Anna-Sophia Scheuermann, Sophia Ruoff, Lara Seitz, Christian Martin Schlegel, Patrick Biomedicines Article CD19CAR T cells facilitate a transformational treatment in various relapsed and refractory aggressive B-lineage cancers. In general, encouraging response rates have been observed in B-lineage-derived non-Hodgkin’s lymphomas treated with CD19CAR T cells. The major cause of death in heavily pretreated NHL patients is lymphoma progression and lymphoma recurrence. Inefficient CAR T cell therapy is the result of the limited potency of the CAR T cell product or is due to loss of the targeted antigen. Target antigen loss has been identified as the key factor that can be addressed stringently by dual- or multitargeted CAR T cell approaches. We have developed a versatile adapter CAR T cell technology (AdCAR) that allows multitargeting. Screening of three different B-lineage lymphoma cell lines has revealed distinct immune target profiles. Cancer-specific adapter molecule combinations may be utilized to prevent antigen immune escape. In general, CD19CAR T cells become non-functional in CD19 negative lymphoma subsets; however, AdCAR T cells can be redirected to alternative target antigens beyond CD19, such as CD20, CD22, CD79B, and ROR-1. The capability to flexibly shift CAR specificity by exchanging the adapter molecule’s specificity broadens the application and significantly increases the anti-leukemic and anti-lymphoma activity. The clinical evaluation of AdCAR T cells in lymphoma as a new concept of CAR T cell immunotherapy may overcome treatment failure due to antigen immune escape in monotargeted conventional CAR T cell therapies. MDPI 2022-09-28 /pmc/articles/PMC9599140/ /pubmed/36289682 http://dx.doi.org/10.3390/biomedicines10102420 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Atar, Daniel
Mast, Anna-Sophia
Scheuermann, Sophia
Ruoff, Lara
Seitz, Christian Martin
Schlegel, Patrick
Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas
title Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas
title_full Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas
title_fullStr Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas
title_full_unstemmed Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas
title_short Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas
title_sort adapter car t cell therapy for the treatment of b-lineage lymphomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599140/
https://www.ncbi.nlm.nih.gov/pubmed/36289682
http://dx.doi.org/10.3390/biomedicines10102420
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