Adoptive immunotherapy using autologous lymphocytes sensitized with HLA class I-matched allogeneic tumor cells.
A 29-year-old female breast cancer patient with multiple bone metastases (HLA-A2) was treated with adoptive transfer using autologous peripheral blood mononuclear cells (PBMCs) activated with the HLA-A2-matched allogeneic GC022588 gastric cancer cell line and interleukin-2 plus an immobilized anti-CD3 antibody culture system. The relief of bone pain in parallel with a decrease of serum carcinoembryonic antigen levels was obtained just after the administration of GC022588-activated effector lymphocytes, and a good quality of life was accomplished for 4 months. The GC022588-activated effector lymphocytes included 44% CD4+, 77% CD8+, and 26% CD4+CD8+ phenotypes, and expressed 25% killing activity against GC022588 stimulator cells at an E/T ratio of 50:1. T cell receptor (TCR) usage analysis for the effector cells showed oligoclonal expression of TCRVbeta1, 3, 9, and 11, especially TCRVbeta5.2, 12, 13.1 and 17, and their killing activity was significantly inhibited in the presence of anti-TCRalphabeta antibody and anti-TCRVbeta12 antibody. SSCP analysis revealed clonotypic bands of TCRVbeta12. These results suggest that shared antigens exist between breast and gastric adenocarcinomas. Allogeneic tumor cells can stimulate PBMCs to generate effector cells with selected TCRCDR3 usages that recognize tumor antigens. These effector lymphocytes may be good candidates for the adoptive immunotherapy of cancer.
Yamaguchi
Yoshiyuki
Y
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan. shogo@hiroshima-u.ac.jp
Ohshita
Akiko
A
Hironaka
Katsuji
K
Okita
Riki
R
Okawaki
Makoto
M
Matsuura
Kazuo
K
Nagamine
Ichiro
I
Ikeda
Takuhiro
T
Ohara
Masahiro
M
Hihara
Jun
J
D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D017690:Cell Transplantation / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000737:chemistry*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D009369:Neoplasms / Q000628:therapy*; D014184:Transplantation, Homologous
D017252:CD3 Complex; D006680:HLA Antigens