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CAR-T Engager Proteins Optimize Anti-CD19 CAR-T Cell Therapies for Lymphoma

Lihe Su, Lan Wu, Roy R. Lobb, View ORCID ProfilePaul D. Rennert, Christine Ambrose
doi: https://doi.org/10.1101/2022.05.30.494010
Lihe Su
Aleta Biotherapeutics, Natick MA USA
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Lan Wu
Aleta Biotherapeutics, Natick MA USA
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Roy R. Lobb
Aleta Biotherapeutics, Natick MA USA
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Paul D. Rennert
Aleta Biotherapeutics, Natick MA USA
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  • For correspondence: paul.rennert@aletabio.com
Christine Ambrose
Aleta Biotherapeutics, Natick MA USA
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Abstract

B cell lymphoma therapy has been transformed by CD19-targeting cellular therapeutics that induce high clinical response rates and impressive remissions in relapsed and refractory patients. However, approximately half of all patients who respond to CD19-directed cell therapy relapse, the majority within six months. One characteristic of relapse is loss or reduction of CD19 expression on malignant B cells. We designed a unique therapeutic to prevent and reverse relapses due to lost or reduced CD19 expression. This novel biologic, a CAR T Engager, binds CD20 and displays the CD19 extracellular domain. This approach increases the apparent CD19 antigen density on CD19-positive/CD20-positive lymphoma cells, and prevents CD19 antigen-oss induced relapse, as CD19 bound to CD20 remains present on the cell surface. We demonstrate that this novel therapeutic prevents and reverses lymphoma relapse in vitro and prevents CD19-negative lymphoma growth and relapse in vivo.

Competing Interest Statement

All authors are employees and/or own stock and/or hold stock options in Aleta Biotherapeutics.

Footnotes

  • Twitter @PDRennert

  • Declaration of interest: All authors are employess and own stock and/or stock options in Aleta Biotherapeutics. In accordance with Journal and Publisher guidelines the authors declare this financial interest and further declare that research conducted may benefit Aleta Biotherapeutics. We have adopted ethical guidelines to prevent conflicts of interest from influencing our research.

  • ↵1 These authors contributed equally to the work described.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 30, 2022.
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CAR-T Engager Proteins Optimize Anti-CD19 CAR-T Cell Therapies for Lymphoma
Lihe Su, Lan Wu, Roy R. Lobb, Paul D. Rennert, Christine Ambrose
bioRxiv 2022.05.30.494010; doi: https://doi.org/10.1101/2022.05.30.494010
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CAR-T Engager Proteins Optimize Anti-CD19 CAR-T Cell Therapies for Lymphoma
Lihe Su, Lan Wu, Roy R. Lobb, Paul D. Rennert, Christine Ambrose
bioRxiv 2022.05.30.494010; doi: https://doi.org/10.1101/2022.05.30.494010

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