Use of a Single CAR T Cell and Several Bispecific Adapters Facilitates Eradication of Multiple Antigenically Different Solid Tumors.
Cancer Res
; 79(2): 387-396, 2019 01 15.
Article
em En
| MEDLINE
| ID: mdl-30482775
ABSTRACT
Most solid tumors are comprised of multiple clones that express orthogonal antigens, suggesting that novel strategies must be developed in order to adapt chimeric antigen receptor (CAR) T-cell therapies to treat heterogeneous solid tumors. Here, we utilized a cocktail of low-molecular-weight bispecific adapters, each comprised of fluorescein linked to a different tumor-specific ligand, to bridge between an antifluorescein CAR on the engineered T cell and a unique antigen on the cancer cell. This formation of an immunologic synapse between the CAR T cell and cancer cell enabled use of a single antifluorescein CAR T cell to eradicate a diversity of antigenically different solid tumors implanted concurrently in NSG mice. Based on these data, we suggest that a carefully designed cocktail of bispecific adapters in combination with antifluorescein CAR T cells can overcome tumor antigen escape mechanisms that lead to disease recurrence following many CAR T-cell therapies. SIGNIFICANCE:
A cocktail of tumor-targeted bispecific adapters greatly augments CAR T-cell therapies against heterogeneous tumors, highlighting its potential for broader applicability against cancers where standard CAR T-cell therapy has failed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Receptores de Antígenos de Linfócitos T
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Imunoterapia Adotiva
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Receptores de Antígenos Quiméricos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2019
Tipo de documento:
Article