Treatment of hepatocellular carcinoma utilizing lymphokine-activated killer cells and interleukin-2

Abstract

This paper is a report on adoptive immunotherapy involving consecutive injections of recombinant interleukin-2 and lymphokine-activated killer (LAK) cells in the treatment of hepatocellular carcinoma. Peripheral blood lymphocytes, obtained by leukopheresis, acted as the activated killer cells with a co culture of recombinant interleukin-2 in the culture system. After 4 days, the activated killer cells were returned into the patients' bodies intra-arterially and intravenously. No complete remissions or partial remissions have resulted, although five of the seven patients showed a significant decrease in their serum alpha-fetoprotein levels after treatment. In addition, one case showed a patent portal truncus while another indicate the appearance of central necrosis on the computerized tomograph scan. Although the period of observation was short, there were no recurrences after the combination therapy of tumor resection and LAK adoptive immunotherapy. It might be difficult to treat hepatocellular carcinoma with adoptive immunotherapy alone, but there is some possibility of conducting therapy for hepatocellular carcinoma after removing the majority of the tumor cells by surgical resection and transcatheter arterial embolization therapy. This conclusion indicates, at least theoretically, that adoptive immunotherapy will be suitable in the treatment of hepatocellular carcinoma as one of the combination therapies with the two major forms of treatment mentioned above.

B7-1 (CD80)-gene transfer combined with interleukin-12 administration elicits protective and therapeutic immunity against mouse hepatocellular carcinoma

“…BNL-mB7-1 exhibited the same growth rate as BNL, indicating that introduction of the murine B7-1 gene did not affect cell proliferation. HCC is generally considered to be one of the poorly immunogenic cancers, because several types of immunotherapy have been tried including lymphokine-activated killer cells 4,5 and OK-432, 6,7 with poor results. Donawho et al reported that an experimental tumor could be considered as poorly immunogenic if immunization with the tumor cells did not induce a statistically significant reduction in the developing tumor in the syngeneic immunocompetent mice.…”

“…[1][2][3] To improve prognosis, some way must be found to prevent the occurrence of second primary tumors. Because several types of immunotherapy have been used against HCC with only poor results, [4][5][6][7] HCC is generally considered to be one of the poorly immunogenic cancers. Accumulating evidence suggests that the reason why the host immune system cannot eradicate tumors is not the absence of recognizable tumor antigens, but rather the inability of these antigens to stimulate an effective immune response.…”

CD80 transfected human hepatocellular carcinoma cells activate cytotoxic T lymphocytes to target HCC cells with shared tumor antigens

“…Several types of immunotherapy including lymphokine-activated killer (LAK) cell injections have been used for HCC treatment. However, no satisfactory results were obtained (5)(6)(7)(8), as HCC is generally considered a very non-immunogenic cancer.…”