Prosthetic antigen receptors

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Chimeric antigen receptors (CARs) have shown great promise for the immunological treatment of cancer. Nevertheless, the need to genetically engineer a patient's T-cells has presented significant production and safety challenges. To address these issues, we have demonstrated that chemically self-assembled nanorings (CSANs) displaying single chain antibodies can bind to both the CD3 e subunit of the T-cell-receptor/CD3 complex and the CD22 antigen on malignant B cells such as B-leukemias or lymphomas. We demonstrate that the multivalent and bispecific format allows the antiCD3/antiCD22 CSANs to stably bind to T-cell surfaces for greater than 4 days, while being easily disassembled on the cell membrane by treatment with the nontoxic FDA approved drug, trimethoprim. In the presence of CD22+ Raji cells, T-cells modified with antiCD3/antiCD22 CSANs were shown to selectively up-regulate the production of interleukin-2 (IL-2) and interferon- (IFN-) and to initiate cytotoxicity. Taken together, our results demonstrate that antiCD3/antiCD22 bispecific CSANs offer a potential alternative to CARs, as prosthetic antigen receptors.

Original languageEnglish (US)
Pages (from-to)10108-10111
Number of pages4
JournalJournal of the American Chemical Society
Volume137
Issue number32
DOIs
StatePublished - Aug 19 2015

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Nanorings
Antigen Receptors
T-cells
Antigens
Prosthetics
T-Lymphocytes
Sialic Acid Binding Ig-like Lectin 2
CD3 Antigens
Single-Chain Antibodies
Trimethoprim
T-Cell Antigen Receptor
Interferons
Interleukin-2
Lymphoma
Leukemia
B-Lymphocytes
Up-Regulation
Cell membranes
Cytotoxicity
Cell Membrane

Cite this

Prosthetic antigen receptors. / Shen, Jingjing; Vallera, Daniel A; Wagner, Carston R.

In: Journal of the American Chemical Society, Vol. 137, No. 32, 19.08.2015, p. 10108-10111.

Research output: Contribution to journalArticle

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AB - Chimeric antigen receptors (CARs) have shown great promise for the immunological treatment of cancer. Nevertheless, the need to genetically engineer a patient's T-cells has presented significant production and safety challenges. To address these issues, we have demonstrated that chemically self-assembled nanorings (CSANs) displaying single chain antibodies can bind to both the CD3 e subunit of the T-cell-receptor/CD3 complex and the CD22 antigen on malignant B cells such as B-leukemias or lymphomas. We demonstrate that the multivalent and bispecific format allows the antiCD3/antiCD22 CSANs to stably bind to T-cell surfaces for greater than 4 days, while being easily disassembled on the cell membrane by treatment with the nontoxic FDA approved drug, trimethoprim. In the presence of CD22+ Raji cells, T-cells modified with antiCD3/antiCD22 CSANs were shown to selectively up-regulate the production of interleukin-2 (IL-2) and interferon- (IFN-) and to initiate cytotoxicity. Taken together, our results demonstrate that antiCD3/antiCD22 bispecific CSANs offer a potential alternative to CARs, as prosthetic antigen receptors.

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