Comparison of cellular immunotherapies and anti-CD3 in the treatment of MCA-38-LD experimental hepatic metastases in C57BL/6 mice.
An experimental model of hepatic metastases in C57BL/6 mice was used to compare the antitumor effects of lymphokine-activated killer (LAK) cells, anti-CD3-activated T-cells (ATC), and anti-CD3 alone. Liver metastases were produced by in vivo passage of MCA-38-LD adenocarcinoma via the ileocolic vein. LAK cells and ATC were generated by 3-day in vitro incubation of spleen cells in interleukin 2 and anti-CD3, respectively. Percentage of tumor volume in livers was determined with a morphometric technique. With less than therapeutic LAK cell doses (0.5-1.0 x 10(7) cells), no effect was seen in mean (+SE, -SE) percentage of tumor volume of control [23.3 (29.3, 18.5)] compared to LAK cell-treated [21.6 (29.3, 15.9)] animals. The same number of ATC significantly reduced the mean percentage of tumor volume [2.7 (4.7, 1.4)] (P less than 0.005). High dose interleukin 2 also significantly decreased tumor volume. More strikingly, a single dose of anti-CD3 alone had a beneficial effect on mean percentage of tumor volume when given i.p. [1.0 (1.9, 0.4)] or i.v. [1.2 (1.7, 0.7)] (P less than 0.0003). A total of 33% of anti-CD3-treated mice had no detectable liver metastases. In 51Cr release assays, the cytotoxicity of ATC was shown to be partially mediated by nylon wool-adherent accessory cells. The effectiveness of anti-CD3 in this immunotherapy model suggests that a similar approach may be taken to immunotherapy of human malignancies, without the requirements for in vitro-generated killer cells or exogenously administered interleukin 2.
Gallinger
S
S
Division of Molecular Immunology and Neurobiology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.
Hoskin
D W
DW
Mullen
J B
JB
Wong
A H
AH
Roder
J C
JC
D000230:Adenocarcinoma / Q000628:therapy*; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001932:Brain Neoplasms / Q000628:therapy*; D017252:CD3 Complex; D002460:Cell Line; D003110:Colonic Neoplasms / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy; D008748:Methylcholanthrene; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D008748:Methylcholanthrene