Clinical and experimental studies of monoclonal antibody to liver metastasis

1994 Fiscal Year Final Research Report Summary

• Project/Area Number: 04670758
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Chiba Uni.,
• Principal Investigator: MATSUBARA Hiromasa Dep.of 2nd Surg., Chiba Uni., Sch.of Med., Assistant, 医学部・附属病院, 助手 (10261926)
• Co-Investigator(Kenkyū-buntansha): ISONO Kaichi Dep.of 2nd Surg., Chiba Uni., Sch.of Med.Professor, 医学部, 教授 (70009489) ; MATSUBARA Hisahiro Dep.of 2nd Surg., Chiba Uni., Sch.of Med.Fellow, 医学部・附属病院, 医員
• Project Period (FY): 1992 – 1994
• Keywords: liver metastasis / intraarterial infusion system / catheter for intraarterial infusion system / monoclonal antibody

Research Abstract

It is studied the efficacy of intraarterial infusion therapy with an anti-cancer agent or monoclonal antibody for liver metastasis to prevent a frequent recurrence after resection of liver metastasis.
1. Experimental study : A human monoclonal antibody 4G12, which was developed by fusion of regional lymph node cells of lung cancer patient and non-secreting myeloma cell line of mouse, was studied for the efficacy. Immunohistochemical studies were performed with 98 human tissue sections. 4G12 highly reacted to esophageal squamous cell carcinoma (55/58,94.8%) and also to several adenocarcinomas of the stomach and colon. However none of normal esophageal tissue was stained. The study of cell-binding assay also confirmed reactivity of 4G12 to human squamous cell carcinoma cell line. In vivo, organ distribution and radiommunoscintigraphy were studied in nude mice bearing human esophageal cancer xenograft. Following i.v.administration of 1.7 MBq/body^<125>I-4G12, tumor/blood ratio reached a ma ximum of 4.24<plus-minus>0.19 at day 5. Radioimmunoscinti graphy showed the accumulation of radiolabeled 4G12 in the region of xenografted esophageal cancer, whereas radiolabeled non-specific human lgM was not accumulated in the cancer regions. The human monoclonal antibody 4G12 might become one of the useful tools for intraarterial infusion therapy.
2. Clinical study : At first, a system of informed consent had settled. In the choice of hepatic resection for colorectal cancer patients with liver metastases, it is specifically effective for thecases with synchronous H1 solitary liver metastasis, and post-operative intraarterial infusion therapy of MMC and ADM was recommended for metachronous liver metastasis. Complications and its management in the intraarterial infusion therapy were investigated. The complications of catheter thrombosis were most frequently observed in the patients with no knots of catheter tip. However, few complication was confirmed by inserting and locating catheter with tip knots.
3. Prospective study : In Japan, the trial of gene therapy has started, and we have already taken an approach to examine the feasibility of gene therapy. It is expected an application of monoclonal antibody for development of drug delivary system, and expected an efficacy of intraarterial infusion system for channel of gene therapy.