Treatment for unresectable hepatoma via selective hepatic arterial infusion of lymphokine-activated killer cells generated from autologous spleen cells

Okuno, Kiyotaka; Takagi, Hiromi; Nakamura, Tsubasa; Nakamura, Yohsuke; Iwasa, Zenji; Yasutomi, Masayuki

doi:10.1002/1097-0142(19860901)58:5<1001::aid-cncr2820580502>3.0.co;2-k

Cited by 54 publications

(11 citation statements)

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“…This provides a rationale for defining the optimal conditions for LAK cell generation in those cancers that may be potentially responsive to LAK/IL-2 therapy. The recently reported studies of adoptive immunotherapy with LAK cells plus rIL-2 achieved a response rate of about 15% for colon cancer (7), only one partial response in five patients with hepatocellular carcinoma (9) and, in another study, a transient effect in a patient with hepatoma treated with locoregionally administered LAK cells (10). This investigation shows that LAK cells with in uitro cytolytic capabilities equal to those of normal controls can be generated from peripheral blood lymphocytes of patients with liver metastases of different histologic types as well as primary malignant hepatic neoplasms.…”

Section: Discussionmentioning

confidence: 96%

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Lymphokine-activated killer cell activity in patients with primary and metastatic malignant liver tumors

et al. 1989

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Lymphokine-activated killer cells were generated from peripheral blood mononuclear cells of 33 patients with liver tumors (benign, 6; primary malignant, 10; metastatic, 17) and 10 healthy individuals. Although peripheral blood mononuclear cell yield was significantly lower (p less than 0.01) in patients with hepatocellular carcinoma or with metastatic colorectal cancer, natural killer activity in the peripheral blood mononuclear cell fraction was comparable in all groups tested. Optimal lymphokine-activated killer activity was demonstrated after 9 to 12 days of culture in recombinant interleukin 2. Lymphokine-activated killer activity, interleukin 2-induced lymphocyte proliferation and total lytic activity generated per culture in all patient groups studied were similar to those of normal control cells cultured under the same conditions. These in vitro data demonstrate the feasibility of obtaining lymphokine-activated killer cells from the blood of patients with liver tumors and provide a rationale for the future use of lymphokine-activated killer cells in adoptive immunotherapy of patients with primary and metastatic hepatic neoplasms.

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Section: Discussionmentioning

confidence: 96%

“…Complete tissue culture medium (TCM) consisted of RPMI 1640 supplemented with 2 mM L-glutamine, 100 units per ml penicillin, 100 pg per ml streptomycin, 10 221 concentration with fresh TCM plus rIL-2. LAK cultures were maintained for up to 15 days.…”

Section: Methodsmentioning

confidence: 99%

Lymphokine-activated killer cell activity in patients with primary and metastatic malignant liver tumors

et al. 1989

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“…Few of these have yet been translated into clinical practice. Low but consistent levels of clinical response were demonstrated using interleukin‐2 and lymphocyte‐ activated killer cells, 131 , 132 and specific immunotherapy using tumour‐specific, ex vivo ‐expanded, cytotoxic T lymphocytes was thought to provide more effective antitumour therapy 133 . Whether the reduction in tumour recurrence of 41%, reported by Takayama et al 134 .…”

Section: Treatment Selection For Hepatocellular Carcinomamentioning

confidence: 97%

Non‐surgical treatment of hepatocellular carcinoma

Alsowmely¹,

Hodgson²

2002

Aliment Pharmacol Ther

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Primary hepatocellular cancer is a disease with a poor prognosis for which there is little consensus on treatment and a paucity of comparative trials. The coexistence of cancer with cirrhosis complicates treatment, and also confers a high risk for the development of further tumours. Surgery, either by hepatic resection or orthotopic liver transplantation, is only a feasible option in a minority of patients. This article surveys the non‐surgical approaches to the treatment of hepatocellular cancers—local ablation techniques, arterial embolization with and without chemotherapy, conventional chemotherapy and hormonal modulation, and targeted and external irradiation.

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“…[2][3][4][5][6][7][8][9][10][11] Meanwhile, as a result of the remarkable advance and popularization of various diagnostic imaging methods, the number of hepatocellular carcinoma (HCC) detected has been increasing and has been successfully resected. [15][16][17] Occasionally, HCCs with marked lymphocyte infiltration have been found among the resected tumors, [18][19][20][21][22][23] but their clinicopathologic characteristics have not been fully clarified.…”

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confidence: 99%

Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration

et al. 1998

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We examined the clinicopathologic features of 11 surgically resected hepatocellular carcinomas (HCCs) less than 3 cm in diameter with marked inflammatory cell infiltration (LHCCs). In comparison with the other 152 HCCs without such an infiltration (controls), there were no significant differences in male/female ratio, age, serum ␣-fetoprotein levels, and laboratory and imaging findings. All the 11 LHCC cases were hepatitis B surface antigen (HBsAg) negative and hepatitis C virus antibody positive. Among the 152 controls, 116 cases were also HBsAg negative and HCVAb positive and were referred to as HCV-only controls. The clinical features were not significantly different between the LHCC and the HCV-only controls. The LHCC group tended to have higher numbers of lymphocytes and monocytes in pre-and post-operative peripheral blood, but there were no significant group differences. Recurrence rate was 9.1% in the LHCC group, 47.7% in the controls and 47.5% in the HCV-only controls (P F .01). Five-year survival rate was 100% in the LHCC group, 65.1% in the controls and 68.1% in the HCV-only controls (P Ͻ .01). Histologically, remarkable inflammatory cell infiltration, mostly lymphocytic, was observed in the cancerous tissue of the LHCC group. Varying degrees of piecemeal necrosis of cancer nests produced by infiltrating lymphocytes were observed in all the 11 cases. Lymph follicle formation was also found in 10 of 11 cases (90.9%). Liver cirrhosis was associated in 6 LHCC cases (54.5%), in 117 control cases (77.0%), and in 91 HCV-only controls (78.4%). Tumor invasion into the portal vein in the vicinity of the tumor was found in 1 LHCC case (9.1%), in 54 controls (35.5%), and in 34 HCV-only controls (29.3%). Immunohistochemically, most of the infiltrating lymphocytes, other than those in the lymph follicle, were identified as T lymphocyte, and CD8 ؉ T lymphocyte was more predominant than CD4 ؉ T lymphocyte. Better prognosis of the LHCC group could attribute to the anti-tumor effect induced by cellular immunity of CD8 ؉ and CD4 ؉ T lymphocytes, and partly by humoral immunity of B cells which formed lymph follicles. (HEPATOLOGY 1998;27:407-414.)When tumor tissues are associated with tumor-infiltrating lymphocytes at a high density or with sinus histiocytosis in its regional lymph node at a high intensity, good postoperative survival rates for cancers have been reported in various organs. [1][2][3][4][5][6] As a mechanism of the good survival, involvement of anti-tumor effect via cellular immunity mainly of T lymphocyte and via humoral immunity of B lymphocyte, or of cytokines produced by the cancer cell itself, has been considered. [2][3][4][5][6][7][8][9][10][11] Meanwhile, as a result of the remarkable advance and popularization of various diagnostic imaging methods, the number of hepatocellular carcinoma (HCC) detected has been increasing and has been successfully resected. [15][16][17] Occasionally, HCCs with marked lymphocyte infiltration have been found among the resected tumors, 18-23 but their clinicopathologic ...

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Treatment for unresectable hepatoma via selective hepatic arterial infusion of lymphokine-activated killer cells generated from autologous spleen cells

Cited by 54 publications

References 13 publications

Lymphokine-activated killer cell activity in patients with primary and metastatic malignant liver tumors

Lymphokine-activated killer cell activity in patients with primary and metastatic malignant liver tumors

Non‐surgical treatment of hepatocellular carcinoma

Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration

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