Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells
Yoshiyuki Takahashi, … , Michael I. Lerman, Richard W. Childs
Yoshiyuki Takahashi, … , Michael I. Lerman, Richard W. Childs
Published February 21, 2008
Citation Information: J Clin Invest. 2008;118(3):1099-1109. https://doi.org/10.1172/JCI34409.
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Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells

Abstract

Transplanted donor lymphocytes infused during hematopoietic stem cell transplantation (HSCT) have been shown to cure patients with hematological malignancies. However, less is known about the effects of HSCT on metastatic solid tumors. Thus, a better understanding of the immune cells and their target antigens that mediate tumor regression is urgently needed to develop more effective HSCT approaches for solid tumors. Here we report regression of metastatic renal cell carcinoma (RCC) in patients following nonmyeloablative HSCT consistent with a graft-versus-tumor effect. We detected RCC-reactive donor-derived CD8+ T cells in the blood of patients following nonmyeloablative HSCT. Using cDNA expression cloning, we identified a 10-mer peptide (CT-RCC-1) as a target antigen of RCC-specific CD8+ T cells. The genes encoding this antigen were found to be derived from human endogenous retrovirus (HERV) type E and were expressed in RCC cell lines and fresh RCC tissue but not in normal kidney or other tissues. We believe this to be the first solid tumor antigen identified using allogeneic T cells from a patient undergoing HSCT. These data suggest that HERV-E is activated in RCC and that it encodes an overexpressed immunogenic antigen, therefore providing a potential target for cellular immunity.

Authors

Yoshiyuki Takahashi, Nanae Harashima, Sachiko Kajigaya, Hisayuki Yokoyama, Elena Cherkasova, J. Philip McCoy, Ken-ichi Hanada, Othon Mena, Roger Kurlander, Tawab Abdul, Ramaprasad Srinivasan, Andreas Lundqvist, Elizabeth Malinzak, Nancy Geller, Michael I. Lerman, Richard W. Childs

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Figure 7

Expression of CT-RCC-8 and CT-RCC-9 in tumors and nonmalignant tissues.

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Expression of CT-RCC-8 and CT-RCC-9 in tumors and nonmalignant tissues. ...
CT-RCC-8 and CT-RCC -9 were found to be expressed only in RCC cells and not a variety of different non-RCC tumor cell lines or in any normal tissues. (A) Semiquantitative RT-PCR for CT-RCC-8 and -9 was performed using cDNAs prepared from 14 different human RCC tumor lines. Both CT-RCC-8 and -9 were detected in 8 of 14 RCC cell lines. (B) CT-RCC common region transcripts were detectable in the same 8 RCC cell lines at variable levels by quantitative real-time RT-PCR analysis using primers and probes specific to CT-RCC common region. (C) Lack of expression of CT-RCC-8 and -9 transcripts by RT-PCR in a variety of different non-RCC malignant cell lines. (D) Neither transcript was detected by RT-PCR in pooled cDNAs obtained from 24 normal human tissues, including the kidney and testis. β-Actin was used as an internal control, and cDNA from SAUJ-RCC was used as a positive control.