Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
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.
View: Text | PDF | Corrigendum
Research Article Oncology Article has an altmetric score of 22

Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells

  • Text
  • PDF
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

×

Figure 3

Characterization and generation of tumor-reactive CTLs.

Options: View larger image (or click on image) Download as PowerPoint
Characterization and generation of tumor-reactive CTLs.
CTLs and T cell ...
CTLs and T cell clones that killed patient RCC cells were isolated using PBMCs collected after transplant and stimulated in vitro with irradiated patient tumor cells. (A) A CTL line was expanded from RCC patient LYO by stimulating posttransplant day +211 PBMCs collected following tumor regression with irradiated LYO-RCC cells; a 51Cr release assay showed these CTLs had in vitro cytotoxicity against both patient LYO-LCL and LYO-RCC cells but not donor (LYOD) LCL cells. (B) SAUJ-CTLs generated by stimulating SAUJ day +1,213 PBMCs with irradiated SAUJ RCC cells killed SAUJ-RCC cells but not SAUJ-LCL cells, SAUJ-fibroblasts (SAUJ-Fibro), K562 cells, or a third-party HLA-mismatched RCC cell line. (C) SAUJ-CTLs secreted IFN-γ when cultured with patient SAUJ-RCC cells but not with SAUJ-Fibro, K562 cells, or patient (SAUJ) or donor (SKEM) LCL cells. (D) IFN-γ production by the SAUJ-CTLs following coculture with SAUJ-RCC cells was inhibited by incubation with anti–HLA class I and anti–HLA-A11 mAbs. (E) Flow cytometry revealed CD8+TCR-Vβ7+ cells to be the dominant T cell population in the SAUJ-CTL line. (F) SAUJ-CTL clone BZ-4 was cocultured with various HLA-A11+ RCC cell lines, with tumor recognition assessed by an ELISA measuring IFN-γ secretion; the BZ-4 clone recognized 5 of 10 HLA-A11+ RCC cell lines. (G) A cytotoxicity assay showed that the BZ-4 clone also killed all 5 HLA-A11+ RCC lines recognized in the ELISA assay but not SAUJ-LCL or K562 cells.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 1 news outlets
Blogged by 1
Referenced in 3 patents
166 readers on Mendeley
1 readers on CiteULike
See more details