title: 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.affiliation: Hematology Branch and Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, Surgery Branch, National Cancer Institute, Department of Clinical Pathology, Clinical Center, Bethesda, Maryland 20892, USA.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Nanae
authors.initials: N
authors.lastname: Harashima
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kajigaya
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Elena
authors.initials: E
authors.lastname: Cherkasova
authors.forename: J Philip
authors.initials: JP
authors.lastname: McCoy
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hanada
authors.forename: Othon
authors.initials: O
authors.lastname: Mena
authors.forename: Roger
authors.initials: R
authors.lastname: Kurlander
authors.forename: Abdul
authors.initials: A
authors.lastname: Tawab
authors.forename: Tawab
authors.initials: T
authors.lastname: Abdul
authors.forename: Ramaprasad
authors.initials: R
authors.lastname: Srinivasan
authors.forename: Andreas
authors.initials: A
authors.lastname: Lundqvist
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Malinzak
authors.forename: Nancy
authors.initials: N
authors.lastname: Geller
authors.forename: Michael I
authors.initials: MI
authors.lastname: Lerman
authors.forename: Richard W
authors.initials: RW
authors.lastname: Childs
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D020077:Endogenous Retroviruses / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014184:Transplantation, Homologous
chemical_list: D000956:Antigens, Viral