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Original Articles
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Local Immunotherapy to Treat Metastatic Liver Cancer by Biodegradable Microspheres Containing Interleukin - 2
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Kwang Wook Suh, Justin S Hanes
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J Korean Cancer Assoc. 1999;31(6):1246-1252.
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Abstract
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- PURPOSE
We tried to elucidate antitumor effect of interleukin-2 containing miscrospheres (IL-2 MS) against intrahepatic challenge of parental cancer cells, which is clinically relevant tumor model.
MATERIALS AND METHODS
Using a model of liver metastasis by intrahepatic challenge of CT-26 murine colon carcinoma cells to syngeneic BALB/c mice, IL-2 MS were given with parental tumor cells, or intratumorally in animals with established tumors. Tumor volume and survivals were determined.
RESULTS
Animals receiving IL-2 MS showed significant tumor suppression effect and systemic protection against the hepatic challenge of parental tumor cells after concomitant challenge with parental CT-26. In animals with established hepatic tumors, significant prolongation in survival was noted.
CONCLUSION
IL-2 MS was effective for the protection of host agaisnt the metastatic hepatic tumor when administered with tumor cells. Its efficacy against the established tumor was also significant as in protection. Locally administered IL-2 MS can obviate the high- efficiency gene transfer technique and ex vivo culture of autologous tumor cells in gene transduced autologous tumor vaccine. It can also provide support for the specific immuno- therapy for the metastatic liver cancer.
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The Effect of Immunotherapy Based on Interferon - alpha in Advanced Renal Cell Carcinoma
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Seung Hyun Jeon, Sung Goo Chang
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J Korean Cancer Assoc. 1999;31(5):986-994.
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Abstract
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- PURPOSE
Recently in light of the development in immunology, interferon- e and inter- leukin-2 or combination therapy with anticancer drugs have been performed. This study aims to verify and compare the efficacy of therapies using interferon- a alone, interferon- a plus vinblastine, and interferon- a plus interleukin-2 plus 5-fluorouracil (5-FU) plus 13-cis retinoic acid (13cRA) in patients with advanced renal cell carcinoma.
MATERIALS AND METHODS
A total of 29 patients were randomly assigned to receive treatment with either interferon- a alone or interferon- a plus vinblastine or interferon- a plus interleukin-2 plus 5-FU plus 13cRA from December 1989 to May 1998. The most frequent metastatic sites were the lung, lymph nodes, bone, liver, and brain. We studied the response rates, survival period, and complications of each regimen.
RESULTS
Responses were achieved in 1 out of 1~5 patients (6.73?o) on interferon- a alone (partial responses lasting 13 months), 1 out of 9 patients (11.1%) on interferon- e plus vinblastine (partial responses lasting 25 months) and 1 out of 5 patients (20.0%) on interferon-a plus IL-2 plus 5-FU plus 13cRA regimen (partial responses lasting 14 months). The median durations of survival were 18, 33, and 23 months respectively. The overall response rate was 10.3% and overall median duration of survival was 19 months. The most common side effects were flu-like symptom such as fever, chills (93.1%), skin symptom such as erythema, pruritus (31.0%), G-I symptom such as nausea, vomiting (17.2%), netropenia (10.3%), abnormal LFT (10.3%), and thrombocytopenia (3.4%).
CONCLUSIONS
This study confirms the manageability and tolerability of several regimen used. There is no significant differences in response rates and survival duration among the regimens used in this study. The effective immunotherapy in patients with metastatic RCC should be evaluated by further studies of larger patients groups even though a minority of patients responded.
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Effects of Interleukin-2 Transduction into the Human Hepatoma Cell Lines Using Retroviral Vector
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Soo Jung Gong, Nae Chun Yoo, Joo Hang Kim, Dong Hwan Shin, Hyo Dong Uhm, Sook Jung Jeong, Jae Yong Cho, Sun Young Rha, Yeon Soo Kim, Hyun Cheol Chung, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim
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J Korean Cancer Assoc. 1997;29(4):555-564.
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Abstract
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- PURPOSE
We compared the differences between parent hepatoma cell lines and interleukin-2 (IL-2) transduced hepatoma cell lines using N2A/IL-2 and LNC/IL-2 retrovirus with regards to in vitro sensitivity to peripheral blood monocytes and in vivo tumorigenic activity.
MATERIALS AND METHODS
Retroviral vector and producer cell line were constructed and IL-2 gene was transduced into the human hepatoma cell lines (SK-Hep1, Hep-G2, Hep-3B). IL-2 secretion after IL-2 transduction was measured by ELISA. MTT assay for in vitro sensitivity to peripheral blood monocytes was performed and the tumorigenic activity was observed in BALB/c mice and nude mice.
RESULTS
IL-2 secretion was 186 pg/10 degrees C cells/24 hrs in SK-Hep1 cell line and was 147 pg/10 (6) cells/24 hrs in Hep-3B cell line with N2A/IL-2 retroviral vector and was 55,000 pg/10 (6) cells/24 hrs with LNC/IL-2 retroviral vector. In vitro sensitivity to peripheral blood monocytes was increased by 163.8~254% in IL-2 transduced hepatoma cell lines (Hep -3B/N2A/IL-2, Hep-G2/N2A/IL-2) compared to those of the parent cell lines. The tumorigenicity was observed in 1 of 3 BALB/c mice and all 3 nude mice. Simultaneous injection of 1 X 10 (7) cells of the parent cell line (Hep-3B) into the right flank and IL-2 transduced cell line (Hep-3B/LNC/IL-2) into the left flank of the three BALB/c mice and of 5 X 10 (5) cells for the three nude mice resulted in a complete regression of the IL-2 modified tumor cell line (Hep-3B/LNC/IL-2) in 3 weeks and the parent cell line (Hep-3B) in 5 weeks. But, after the injection of 1.5 X 10 (7) cells for other five nude mice, the tumor of the IL-2 transduced hepatoma cell line (Hep-3B/LNC/IL-2) was gradually disappeared, and the tumor of the parent hepatoma cell line (Hep-3B) was initially decreased and then gradually regrew 20 days later.
CONCLUSION
IL-2 transduced hepatoma cell lines secreting IL-2 became more sensitive to peripheral blood monocytes and resulted in the increased antigenicity to the tumors formed by IL-2 transduced hepatoma cell line and parent cell line, and finally resulted in the regression of the tumors in experimental animals.
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Clinical Trial of Human Recombinant Interleukin-2 ( IL-2
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Joung Soon Jang, Jae Bum Jun, Joon Soo Hahm, Min Ho Lee, Il Young Choi, Te June Chung
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J Korean Cancer Assoc. 1990;22(1):96-106.
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Abstract
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- The effects of immunotherapy with IL-2 were evaluated in 10 patients with advanced cancers for whom standard anticancer chemotherapy had been ineffective from Apr. 1988 to Mar. 1989. Of total 10 patients, five were treated witn 24 hr continuous IV infusion of IL-2 with the dosage of 1 x 10(4) u/kg/day or 1 x 10(5) u/kg/day respectively for 5 days and another five with intraperitoneal bolus infusion of IL-2 with the dosage of 1 x10(4) u/kg/day or 1 x 10(5) u/kg/day after removal of ascites by paracenthesis for 5 days. Of the 10 evaluable patients, 9 (90%) patients had no response and only 1 (10%) had minimal response. One patient who had minmal response had squamous cell ca of esophagus and has received IL-2 intravenously. Most common side effects were fever and chills and they could be prevented or alleviated by use of NSAIDs or IV infusion of Meperidine in severe cases. Serious side effects were capillay leak syndrome and its complication which show hypotension, generalized edema, weight gaine and azotemia. GI symptom, rigor and skin lesion were also obseved. But pulmonary edema was not observed. All of the above side effects were well overcome by conservative management. In the intraperitoneal infusion group the side effects occurred less frequently than IV infusion group. Anemia, neutropenia, eosinophilia, azotemia and abnormal liver function test were observed, but they have returned to normal range after discontinuation of IL-2 infusion. The absolute lymphocyte counts decreased I day after IV infusion of IL-2 and came back to show revound lymphocytosis from the next day after discontinuation of IL-2 infusion. They returned to pretreatment level from the 4th day of discontinuation of IL-2 infusion. In the intraperitoneal infusion group total WBC counts in ascites began to increase from 24 hrs after IL-2 infusion and reached peak at the end day of infusion. They began to decreased with discontinuation of infusion. Compared with WBC counts in ascites, those in peripheral blood showed delayed increase. In conclusion, 1 x 10' and 1 x 10 u/kg/day infusion of IL-2 were enough to increase the lymphocyte pool in vivo respectively, although no effective clinical response was obtained. There was no difference in the clinical and side effects between 1 x 10(4) and 1 x 10(5) u/kg/day infusion groups. This study warrants for further investigation into the determination of effeective therapeutic concentration of IL-2 and its route of adminstration.
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Effects of natural Killer Cell Manupulation on the Metastatic Cancer and Host Immune Response
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Seung Hoon Choi
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J Korean Cancer Assoc. 1996;28(2):368-375.
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Abstract
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- The purpose of this study was to determine the susceptibility of murine Cl300 neuroblstoma to in vivo natural killer(NK) cell mediated cytolysis and to determine if NK cells influence metastasis of this tumor. The role of NK cells in controlling the metastasis af C1300 neuroblastama to the lung was examined in A/J mice. Treatment with Interleukin-2 on days 1 through 5 after C1300 inoculation significantly decreased the tumor growth, inhibited pulmonary metastasis, and enhanced in vitro NK killing of YAC-l.Treatment with gamma Interferon on days 1 through 5 after tumuor inoculation significantly inhibited pulmonary metastasis. Antitumor effects of Interleukin-2 was stronger than that of gamma Interferon. In vivo depletion of NK cells with anti-asialo GMl significantly enhanced tumor growth and decreased host antitumor activity. These results demonstrated that in vivo elinimation of anti-asialo GM1 positive cells increased pulmonary metastasis, and in such mice, there were significant differences in metastatic potential between control and Interleukin-2, gamma Interferon treated groups.
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