Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer.
BACKGROUND
The efficiency of anti-CD3 antibody (OKT3) for adoptive immunotherapy using lymphokine-activated killer (LAK) cells generated from tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) was investigated.


METHODS
TIL, RLNL, and PBL derived from 39 patients with gastrointestinal cancers (16 gastric cancers, 17 colorectal cancers, and 6 esophageal cancers) were cultured for 4 weeks with 200 U/ml of recombinant interleukin-2. To one group, solid-phase 10 micrograms/ml OKT3 was added during the initial culture period (day 2 or 4). Cytotoxicity against K562 cells (NK-like activity) and Daudi cells (LAK activity) and the phenotypes of effector cells generated after culturing for 2-3 weeks were studied.


RESULTS
Proliferative responses were significantly increased by OKT3 in each type of effector cell (P less than 0.01); in particular, TIL expanded more by OKT3 than PBL and RLNL (P less than 0.01). The population of CD8+ CD11b- cytotoxic T-cells in OKT3-stimulated groups was significantly larger than that in unstimulated groups (P less than 0.01), whereas no differences were observed with CD4+ cells (helper/inducer T-cells) and CD8+ CD11b+ cells (suppressor T-cells). OKT3 enhanced the NK-like activity of TIL and PBL but did not affect their LAK activity. OKT3 suppressed the NK and LAK activity of RLNL.


CONCLUSIONS
OKT3 stimulation did not significantly enhance the LAK activity, but the authors propose that OKT3 could be an effective addition to adoptive immunotherapy using TIL due to an increased proliferation and generation of a large cytotoxic T-cell population.
Ohta
T
T
First Department of Surgery, St. Marianna University School of Medicine, Kawasaki, Japan.
Kikuchi
H
H
Ogata
H
H
Iwata
K
K
Yoshida
K
K
Katayama
K
K
Watanabe
H
H
D000368:Aged; D000369:Aged, 80 and over; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D002455:Cell Division / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008214:Lymphocytes / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D016853:Muromonab-CD3; D011948:Receptors, Antigen, T-Cell