Evaluation of immunoffector cells in combination gene therapy of IL-18 and IL-12

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15592142
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Nihon University
• Principal Investigator: MIYAKE Mashiko Nihon University, School of Dentistry, Associate, 歯学部, 講師 (40157615)
• Co-Investigator(Kenkyū-buntansha): KOMIYAMA Kazuo Nihon University, School of Dentistry, Associate, 助教授 (00120452)
• Project Period (FY): 2003 – 2004
• Keywords: gene therapy / oral cancer / MIP-1α / IL-18 / ICE / IL-12 / nu / nu mouse / adenovirus vector

Research Abstract

To investigate a possible immuno-genetherapyfororalcancer, weperformedchemokineandcytokinegene transfection to human oral squamous cell carcinoma cells. Anti-tumor effects studied by the gene-modified tumor cells transplant the nu/nu mice. 1) MIP-1α gene ligated into plasmidexpression vector and transfected with lipofection methodintoHSC-2,-3and-4-fortestingtrasfectionefficiency. Of numerous gene-transfected clones, HSC-3/MIP-1α-C7 was selected and transfected to nu/nu mice. The result indicated that activation of effecter cells and tumorigenecity wereidentifiedinthose gene modified oral cancer transplanted mice. 2) Second immno-genetherapyperformedusingIL-18gene ligated adenovirusvector. IL-18isstrongactivatortoNK, macrophagesandCTLs. IL-18genemodifiedHSCcellswere transplanted to nu/nu mice, which demonstrated reduction of tumor volume compared with control tumor transplantation. But the tumor did not completely regressed from the inoculation site. An augmented antitumor effectwasobtainedbyrecombinantIL-12injectiontotheIL-18genetransfectiontumor bearing mice. Above result indicated that chemokines and cytokine gene therapy excites the innate immunity and possessed strong antitumor effect. The result gives also credit for further tumor vaccination of oral cancer.