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Artificial Antigen Presenting Cells With Preclustered anti-CD28/-CD3/-LFA-1 Monoclonal Antibodies Are Highly Effective To Induce The Ex-Vivo Expansion Of Functional Human Antitumor T Cells

Roberta Zappasodi¹, Massimo Di Nicola¹, Carmelo Carlo-Stella², Roberta Mortarini³, Alessandra Molla³, Claudia Vegetti³, Lorena Passoni³, Salvatore Albani⁴, Andrea Anichini³ & Alessandro M. Gianni¹

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1. Fondazione IRCCS Istituto Nazionale Tumori, "C. Gandini" Medical Oncology, Bone Marrow Transplantation Unit
2. Fondazione IRCCS Istituto Nazionale Tumori, University of Milan, "C. Gandini" Medical Oncology, Bone Marrow Transplantation Unit
3. Fondazione IRCCS Istituto Nazionale Tumori
4. Stephen Chair, Arizona Arthritis Center University of Arizona

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Document Type:

Manuscript

Date:

Received 24 October 2007 10:43 UTC; Posted 24 October 2007

Subjects:

Biotechnology, Cancer, Immunology

Tags:

• artificial antigen presenting cells
• T cells
• immunotherapy

Abstract:

Effective adoptive T cell therapy requires the ex vivo generation of functional T lymphocytes with a long lifespan in vivo. We evaluated in vitro T cell expansion by artificial antigen presenting cells (aAPC) generated with activating (human anti-CD3), co-stimulating (human anti-CD28) and adhesion (human anti-LFA-1) monoclonal antibodies pre-clustered in microdomains (MDs) held by a liposome scaffold. The co-localization of T cell ligands in MDs and the targeting of an adhesion protein, increasing the efficiency of immunological synapse formations, represent the novelties of our system. These aAPCs allowed increased expansion of polyclonal CD4⁺ and CD8⁺ T cells and of tumor antigen-specific CD8⁺ T cells compared to anti-CD28- and anti-CD3-coated microbeads and to immobilized anti-CD3. These aAPCs allowed the generation of T cells displaying an immunophenotype consistent with long-term in vivo persistence, without increasing the frequency of regulatory T cells. Finally, our aAPCs proved to be suitable for large scale T cell expansion required in immunotherapy trials.

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This document is licensed to the public under the Creative Commons Attribution 2.5 License

How to cite this document:

Zappasodi, Roberta, Di Nicola, Massimo, Carlo-Stella, Carmelo, Mortarini, Roberta, Molla, Alessandra, Vegetti, Claudia, Passoni, Lorena, Albani, Salvatore, Anichini, Andrea, and Gianni, Alessandro. Artificial Antigen Presenting Cells With Preclustered anti-CD28/-CD3/-LFA-1 Monoclonal Antibodies Are Highly Effective To Induce The Ex-Vivo Expansion Of Functional Human Antitumor T Cells. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2007.1250.1> (2007)

Version info:

Published version:

10.3324/haematol.12521 (Peer Reviewed) Published as: Roberta Zappasodi, Massimo Di Nicola, Carmelo Carlo-Stella, Roberta Mortarini, Alessandra Molla, Claudia Vegetti, Salvatore Albani, Andrea Anichini, and Alessandro M. Gianni. The effect of artificial antigen-presenting cells with preclustered anti-CD28/-CD3/-LFA-1 monoclonal antibodies on the induction of ex vivo expansion of functional human antitumor T cells. Haematologica 93, 1523-1534 (2008). Available online: August 25, 2008.

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