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T cells expressing VHH-directed oligoclonal chimeric HER2 antigen receptors: Towards tumor-directed oligoclonal T cell therapy

Lookup NU author(s): Professor Moein MoghimiORCiD

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Abstract

Background Adoptive cell therapy with engineered T cells expressing chimeric antigen receptors (CARs) originated from antibodies is a promising strategy in cancer immunotherapy. Several unsuccessful trials, however, highlight the need for alternative conventional binding domains and the better combination of costimulatory endodomains for CAR construction to improve the effector functions of the engineered T cells. Camelid single-domain antibodies (VHHs), which are the smallest single domain antibodies, can endow great targeting ability to CAR-engineered T cells. Methods We have developed a method to generate genetically engineered Jurkat T cells armed with a CAR comprising the anti-HER2 VHH as targeting moiety. From an immune camel library, five VHH clones were selected as a set of oligoclonal anti-HER2 VHHs that exhibited diverse binding abilities and joined them to CD28-CD3ζ and CD28-OX40-CD3ζ signaling endodomains. Jurkat T cells expression of VHH-CARs and cell functions were evaluated. Results The oligoclonal engineered T cells showed higher proliferation, cytokine secretion and cytotoxicity than each individual VHH-CAR-engineered Jurkat T cells. Conclusions The combination of superior targeting ability of oligoclonal VHHs with the third generation CAR can substantially improve the function of engineered T cells. General significance Antigen-specific directed oligoclonal T cells are alternatively promising, but safer systems, to combat tumor cells. © 2013 Elsevier B.V.

Publication metadata

Author(s): Jamnani FR, Rahbarizadeh F, Shokrgozar MA, Mahboudi F, Ahmadvand D, Sharifzadeh Z, Parhamifar L, Moghimi SM

Publication type: Article

Publication status: Published

Journal: Biochimica et Biophysica Acta (BBA) - General Subjects

Year: 2014

Volume: 1840

Issue: 1

Pages: 378-386

Print publication date: 01/01/2014

Online publication date: 27/09/2013

Acceptance date: 20/09/2013

ISSN (print): 0304-4165

ISSN (electronic): 1872-8006

Publisher: Elsevier BV

URL: https://doi.org/10.1016/j.bbagen.2013.09.029

DOI: 10.1016/j.bbagen.2013.09.029

PubMed id: 24076235

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