2000 Fiscal Year Annual Research Report

インターロイキン15を用いた癌免疫療法の開発

Research Project

Project/Area Number	12217059
Research Institution	Nagoya University
Principal Investigator	吉開泰信名古屋大学, 医学部, 教授 (90158402)
Keywords	IL-15 / トランスジェニックマウス / メラノーマ / NK細胞 / CD8キラーT細胞 / DNAワクチン
Research Abstract	IL-15cDNAをMHCクラスIプロモーターと発現ベクターに組み込み、トランスジェニック(Tg)マウスを作製した。このマウスでは脾臓でのメモリー型CD8T細胞数が有意に増加していた。またNK細胞数には差を認めなかったが、YAC-1やMHCクラスI陰性メラノーマB16.44に対して強いNK細胞傷害活性が認められた。IL-15TgマウスにB16.441x10^6を皮下に接種したところ、腫瘍の増殖が著しく抑制された。B16.44接種IL-15Tgマウスに抗asialoGM1抗体を400μgx4回投与で抗腫瘍抑制効果が阻害された。次にIL-15TgマウスにMHCクラスI陽性メラノーマ(B16F10)細胞5x10^4を皮下に接種して、腫瘍増殖曲線を調べたところ、B16.44と同様に強い腫瘍増殖抑制が認められた。B16F10接種10日目の脾臓細胞をさらにマイトマイシン処理B16F10と5日間培養して、B16F10に対する細胞傷害活性を調べたところ、強い細胞傷害活性が認められた。B16F10IL-15Tgマウスに抗CD8抗体を400μgx4回投与で抗腫瘍抑制効果が阻害された。IL-15TgマウスではMHCクラスI陰性メラノーマに対してはNK細胞を、MHCクラスI陽性メラノーマに対してはCD8キラーT細胞の活性化によって抗腫瘍効果を示すことが明かとなった。 IL-15cDNAをpEGFP-N1に組み込んだプラスミドpEGFP-N1:IL-15を作成し、gene gunを用いて4μgをマウスに投与して1日、3日、5日目に局所リンパ節細胞を共焦点レーザー顕微鏡で調べてところ、3日目から付着細胞に蛍光が検出された。そこで、BCG感染後、3日毎に3回pCR3.1:IL-15を投与したところ、有意にPPD特異的CD8T細胞の増加が認められた。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Nishimura,H.: "Differential roles of IL-15 mRNA isoforms generated by alternative splicing in immune responses in vivo."J.Exp.Med.. 191. 157-170 (2000)
[Publications] Kimura,K.: "Synergistic effect of IL-15 and IL-12 on anti-tumor activity in a murine malignant pleurisy model."Cancer.Immunol.Immunother.. 49. 71-77 (2000)
[Publications] Yoshikai,Y.: "The role of interleukin 15 in mounting an immune response against microbial infections."Microbes.Infect.. 2. 381-389 (2000)
[Publications] Mokuno,Y.: "Expression of Toll-like receptor 2 on γδ T cells bearing invariant Vγ6/Vδ1 indyced by Escherichia coli infection."J.Immunol.. 165. 931-940 (2000)
[Publications] Murosaki,S.: "Antitumor effect of heat-killed Lactobacillus plantarum L-137 throuigh restoration of impaired IL-12 production in tumor-bearing mice."Cancer.Immunol.Immunother.. 49. 157-164 (2000)
[Publications] Masuda,A.: "Interleukin-15 induces rapid tyrosine phosphorylation of STAT6 and the expression of interleukin-4 in mouse mast cells."J.Biol.Chem.. 275. 29331-29337 (2000)
[Publications] Matsuguchi,T.: "Gene expression of Toll-like receptor 2 but not Toll-like receptor 4, is induced by LPS and inflammatory cytokines in mouse macrophages."J.Immunol. 165. 5767-5772 (2000)
[Publications] Umemura,M.: "Impaired IL-15 production in murine AIDS mice might uderlie susceptibility to mycobacterial infection."J.Leuko.Biol.. 69. 138-148. (2001)
[Publications] Ishimitsu,R: "Overexpression of Interleukin-15 in vivo enhances Tcl response which inhibits allergic inflammation in a murine model of asthma."J.Immunol.. 166. 1991-2001 (2001)
[Publications] Nishimura,H.: "Mice lacking IL-2/IL-15 receptor β chain are susceptible but mice lacking IL-2 are resistant to infection with avirulent Salmonella choleraesuis."Infect.Immun.. 69. 1226-1229 (2001)
[Publications] Yajima,T.: "Memory phenotype CD8^+T cells increased in IL-15 transgenic mice are involved in early protection against a primary infection with Listeria monocytogenes."Eur.J.Immunol.. (in press.). (2001)
[Publications] Umemura,M.: "Overexpression of IL-15 in vivo induces a predominant Tcl response in mice inoculated with Mycobacterium bovis Bacille Calmette-Guerin infection."J.Immunol.. (in press.). (2001)

2000 Fiscal Year Annual Research Report

インターロイキン15を用いた癌免疫療法の開発

Principal Investigator

吉開 泰信 名古屋大学, 医学部, 教授 (90158402)

Research Products

[Publications] Nishimura,H.: "Differential roles of IL-15 mRNA isoforms generated by alternative splicing in immune responses in vivo."J.Exp.Med.. 191. 157-170 (2000)

[Publications] Kimura,K.: "Synergistic effect of IL-15 and IL-12 on anti-tumor activity in a murine malignant pleurisy model."Cancer.Immunol.Immunother.. 49. 71-77 (2000)

[Publications] Yoshikai,Y.: "The role of interleukin 15 in mounting an immune response against microbial infections."Microbes.Infect.. 2. 381-389 (2000)

[Publications] Mokuno,Y.: "Expression of Toll-like receptor 2 on γδ T cells bearing invariant Vγ6/Vδ1 indyced by Escherichia coli infection."J.Immunol.. 165. 931-940 (2000)

[Publications] Murosaki,S.: "Antitumor effect of heat-killed Lactobacillus plantarum L-137 throuigh restoration of impaired IL-12 production in tumor-bearing mice."Cancer.Immunol.Immunother.. 49. 157-164 (2000)

[Publications] Masuda,A.: "Interleukin-15 induces rapid tyrosine phosphorylation of STAT6 and the expression of interleukin-4 in mouse mast cells."J.Biol.Chem.. 275. 29331-29337 (2000)

[Publications] Matsuguchi,T.: "Gene expression of Toll-like receptor 2 but not Toll-like receptor 4, is induced by LPS and inflammatory cytokines in mouse macrophages."J.Immunol. 165. 5767-5772 (2000)

[Publications] Umemura,M.: "Impaired IL-15 production in murine AIDS mice might uderlie susceptibility to mycobacterial infection."J.Leuko.Biol.. 69. 138-148. (2001)

[Publications] Ishimitsu,R: "Overexpression of Interleukin-15 in vivo enhances Tcl response which inhibits allergic inflammation in a murine model of asthma."J.Immunol.. 166. 1991-2001 (2001)

[Publications] Nishimura,H.: "Mice lacking IL-2/IL-15 receptor β chain are susceptible but mice lacking IL-2 are resistant to infection with avirulent Salmonella choleraesuis."Infect.Immun.. 69. 1226-1229 (2001)

[Publications] Yajima,T.: "Memory phenotype CD8^+T cells increased in IL-15 transgenic mice are involved in early protection against a primary infection with Listeria monocytogenes."Eur.J.Immunol.. (in press.). (2001)

[Publications] Umemura,M.: "Overexpression of IL-15 in vivo induces a predominant Tcl response in mice inoculated with Mycobacterium bovis Bacille Calmette-Guerin infection."J.Immunol.. (in press.). (2001)

吉開泰信名古屋大学, 医学部, 教授 (90158402)