1. ¹Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan
2. ²Department of Gynecology, Aichi Cancer Center Hospital, Nagoya, Japan
3. ³Department of Internal Medicine II, Okayama University Medical School, Okayama, Japan
4. ⁴Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
5. ⁵Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan

Correspondence: Dr Y Akatsuka, Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan

Received 13 April 2004; Accepted 9 August 2004; Published online 21 October 2004.

Abstract

Retroviral vectors are the frequently applied gene delivery vehicles for clinical gene therapy, but specificity of the immunogenicity to the protein encoded by the inserted gene of interest is a problem which needs to be overcome. Here, we describe human cytotoxic T-lymphocyte (CTL) clones recognizing epitopes derived from the protein encoded by the retroviral vector backbone, which were established during the course of our attempts to generate CTLs against cytomegalovirus (CMV) or human papilloma virus (HPV) in vitro. In the case of healthy CMV-seronegative donors, CTL lines specific for retrovirally transduced cells were generated in four out of eight donors by stimulating CD8 T cells with CD40-activated B (CD40-B) cells retrovirally transduced with CMV-pp65. Two CTL clones derived from one of the CTL lines were found to recognize epitopes from gag in the context of HLA-B^*4403 and -B^*4601, respectively. Similarly, an HLA-B^*3501-restricted CTL clone from a cervical cancer patient recognized an epitope located in the junctional regions of the gag and pol sequences. These results show that polypeptides encoded by components of the retroviral vector backbone are in fact immunogenic, generating CTLs in vitro in human cells. Thus, potential CTL responses to retroviral products should also be considered in clinical settings.