Induction of allogeneic tumour- and lymphokine-activated lymphocytes against hepatocellular carcinoma.
For clinical application of adoptive immunotherapy against hepatocellular carcinoma (HCC), it is not easy to prepare tumour specific effector cells such as cytotoxic T lymphocytes (CTL). To induce potent and broad-spectrum effectors, allogeneic cultured hepatoma cell lines (JHH-4 and HuH-6) were used as stimulators of peripheral blood lymphocytes (PBL) instead of autologous HCC cells. Allogeneic tumour- and lymphokine-activated killer cells (ATLAK) were generated by a mixed culture of lymphocytes and allogeneic cultured tumour cells with recombinant interleukin-2 (rIL-2). The tumour-killing activity of ATLAK induced by HuH-6 was confirmed against HuH-6 and other different HCC cell lines (JHH-2, HuH-7 and PLC). These activated lymphocytes were significantly more potent than lymphokine-activated killer cells (LAK) in [51Cr]-releasing assay. The JHH-4 stimulated ATLAK was reactive not only with JHH-4 but also with JHH-2. The lysis of allogeneic targets could be partially inhibited by anti-CD8 and anti-CD3 but not by anti-CD4. Anti-tumour cytotoxicity in these cultures might be mediated by CD3+CD56- and CD3+CD56+ effectors. These results imply that adoptive immunotherapy for HCC with ATLAK may be more feasible than that with LAK.
Yasumura
S
S
Department of Third Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Higuchi
K
K
Hioki
O
O
Okada
K
K
Tsukishiro
T
T
Tsuchida
T
T
Miyagiwa
M
M
Nambu
S
S
Yasuyama
T
T
Inoue
K
K
D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D010641:Phenotype; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation