Springer Protocols: Abstract: 17. Designing TCR for Cancer Immunotherapy

17. Designing TCR for Cancer Immunotherapy

By: Ralf-Holger Voss³, Jürgen Kuball⁴, Matthias Theobald⁵

Abstract

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Reprogramming T-cell populations by T-cell receptor (TCR) gene transfer is a new therapeutic tool for adoptive tumor immunotherapy. Gene transfer of human leukocyte antigen (HLA)-transgenic mice-derived TCR into human T-cells allows the circumvention of tolerance to tumor-associated (self) antigens (TAA). This chapter reports on the identification of the α and β chains of the heterodimeric TCR derived from a mouse T-cell clone. The related DNA fragments are inserted into a retroviral vector for heterologous expression of the TAA-specific TCR in human T-cells. Polymerase chain reaction (PCR)-based cloning protocols are provided for the tailor-made customization of murine TCR. We describe the humanization and chimerization of such TCR as well as their expression in human T-cells.

Affiliation(s): (3) Department of Hematology and Oncology, Johannes Gutenberg-University, Mainz, Germany
(4) Department of Hematology and Oncology, Johannes Gutenberg-University Mainz, Mainz, Germany
(5) Department of Hematology and Oncology, Johannes Gutenberg-University, Mainz, Germany

Book Title: Adoptive Immunotherapy: Methods and Protocols

Series: Methods in Molecular Medicine | Volume: 109 | Pub. Date: Nov-30-2004 | Page Range: 229-256 | DOI: 10.1385/1-59259-862-5:229

Subject: Immunology

Key Words: Cancer therapy - immunotherapy - T-cell receptor - high-affinity TCR - highavidity T-cell - tolerance - human leukocyte antigen - major histocompatibility complex - HLAA*0201 restriction - tumor-associated antigen - HLA-A2 transgenic mice - reverse transcription and polymerase chain reaction - rapid amplification of cDNA ends - single-chain TCR and singlechain Fv - retroviral transduction; packaging cell line 293T and phoenix-ampho - adoptive transfer of T-cells

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