キャンバス Research Memo(4):新パラダイムの免疫系抗がん剤分野でCBP501新臨床試験をスタート
4. 抗がん剤開発動向とパラダイム転換
がん治療分野では、数年来より欧米の学会を中心にパラダイム転換が起きている。がん治療は、過去50年ほどの間に、外科手術が困難なステージまで進行すると、放射線と化学療法(抗がん剤投与)の治療法しかなかった。2000年頃からいわゆる「分子標的薬」=個別化医療が登場し、国内では大手製薬企業、医療行政、マスコミが挙って、“これから分子標的薬の時代が到来する”と大々的に扱われた。一方、欧米の学会ではその後、分子標的薬が大部分の患者に効かないという論文が相次ぎ発表され、分子標的薬の限界が訴えられてきた。
(1)免疫チェックポイント抗体の登場
近年、免疫系抗がん剤(小野薬品工業のオプジーボ®など)の登場で、がん治療法を根本から覆らせるインパクトが生じている。従来の抗がん剤(化学療法、分子標的薬)は「余命を数ヶ月延ばす」ことを積み重ねてきたが、一旦効果が出ても直ぐにがん細胞が復活し、効果が持続しなかった。一方、免疫チェックポイント抗体は「長期生存を年単位で延ばす」こととなり、抗がん剤の開発目標が大きく変わった。更に治癒も望める可能性も出てきている。
既に、欧米では免疫チェックポイント抗体中心の抗がん剤開発競争にシフトしている。国内製薬企業も遅ればせながら重い腰を上げて、免疫系抗がん剤開発に着手している。
免疫チェックポイント抗体の普及のためには、“超高”薬価対策と恩恵を受ける患者比率のアップが当面の課題であり、低コスト対応の低分子化合物免疫系抗がん剤の開発、がん腫の適用拡大や効果予測のマーカーの探索が急務である。
(2)「免疫チェックポイント抗体と他の抗がん剤」の試みが増加
免疫系抗がん剤の課題である「恩恵を受ける患者比率」を高めるために、免疫系抗がん剤と他の抗がん剤の併用の臨床試験が多数進行している。組み合わせとしては、「免疫チェックポイント抗体+免疫チェックポイント抗体」、「免疫チェックポイント抗体+在来の化学療法剤」があるが、前者は、副作用問題と高薬価が課題で、後者は、少数の患者で見る限り良好なデータが得られており、効果のある患者比率が高く、低薬価対応、副作用も問題なく、現時点でベストな方法を考えられている。既に、大手製薬企業(ブリストル・マイヤーズ スクイブ、メルクなど)は免疫系抗がん剤と化学療法剤2剤の併用による大規模臨床試験を進めており、臨床試験結果は2019~2020年に判明する。
5. 同社の新抗がん剤候補化合物の研究開発戦略と新臨床試験計画
(1)臨床試験の取り組みと反省・教訓から得たノウハウ
2013年のCBP501(抗がん剤候補化合物)の肺がん臨床第2相試験では、残念ながら主要評価項目を達成できなかった。しかし改めて当該臨床データを同社の基礎研究チームで解析すると、白血球数の正常な被験者では改善し、白血球数の異常な被験者では悪いことに気付き、白血球数の多寡がCBP501の作用に影響していることが判明した。この解析結果と、それに続く基礎研究成果は、同社の研究開発の方向性を決めるきっかけとなった。
(2)新発見とデータ獲得
近年の臨床試験や解析で同社が獲得したデータのポイントは2つある。1つは、生体内の数多くの分子をあたかも電子楽器のイコライザーのように制御するカルモジュリンという分子の制御機能の調整をするCBP501が、プラチナ系抗癌剤との併用でがん細胞の「免疫原性細胞死」を増やすことである。免疫原性細胞死が増えることは、免疫系抗がん剤の作用を高める効果がある。もう1つは、マクロファージという免疫細胞ががん患者で免疫を抑制する働きをしているところ、CBP501がマクロファージの働きを阻害して、がん細胞の免疫抑制を遮断することである。
(3)「免疫系抗がん剤+化学療法(プラチナ系)+候補化合物CBP501」の併用の可能性
CBP501とプラチナ系抗がん剤(シスプラチン)との併用は過去約200人の患者投与実績があり、副作用の問題はない。また、悪性胸膜中皮腫では主要評価項目をクリアしており、動物実験では高い効果を得ている。
CBP501をベースにした併用案は色々あるが、現時点では免疫系抗がん剤+プラチナ系+CBP501の併用で良い実験結果が得られているようである。
(4)適応がん腫
現在は、非小細胞肺がん、悪性胸膜中皮腫(アスベスト)を中心に検討を進めているが、前回の臨床試験では、卵巣がんにも効果の兆候が見られた。免疫系抗がん剤+プラチナ系で効果があるのは、頭頸部がん、胃がん、食道がん、大腸がん、腎臓がんなどで、ほとんどのがん腫に使われている。
(5) CBP501新臨床試験計画と申請認可
今回のFDA臨床試験(フェーズ1b試験)は、免疫系抗がん剤(抗PD-1免疫チェックポイント阻害抗体)+標準化学療法(プラチナ系/シスプラチン)、CBP501の3剤併用によるオープンラベル・非無作為化・非対照で行う。
安全性の観点から推奨投与量の決定、有効性の観点から治療効果の向上、対象がん患者比率の向上、効果のあるがん腫の発見と確認を行う。
この臨床試験の結果は、大手製薬企業(ブリストル・マイヤーズスクイブ、メルクなど)の大規模臨床試験の結果が出る2019~2020年頃には出る予定で、他社の併用臨床結果との比較が可能になる。
(執筆:フィスコ客員アナリスト 清水 啓司)
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File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
Line: 41
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b3d14aa11_83151422
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
Line: 43
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b47775ef5_14228348
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
Line: 397
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 248
Function: callBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 184
Function: callBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 186
Function: process
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 156
Function: process
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
Line: 88
Function: instanceBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b3cb92fa0_94546305
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 116
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
Line: 71
Function: endChild
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_67089277b12ce9_02546255
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
Line: 238
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
Line: 116
Function: _execute
File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
Line: 45
Function: fetch
File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
Line: 32
Function: view
File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
Line: 292
Function: require_once
A PHP Error was encountered
Severity: Notice
Message: Undefined offset: 1
Filename: smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
Line Number: 41
Backtrace:
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
Line: 41
Function: _error_handler
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b3d14aa11_83151422
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
Line: 43
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b47775ef5_14228348
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
Line: 397
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 248
Function: callBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 184
Function: callBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 186
Function: process
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 156
Function: process
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
Line: 88
Function: instanceBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b3cb92fa0_94546305
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 116
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
Line: 71
Function: endChild
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_67089277b12ce9_02546255
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
Line: 238
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
Line: 116
Function: _execute
File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
Line: 45
Function: fetch
File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
Line: 32
Function: view
File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
Line: 292
Function: require_once
A PHP Error was encountered
Severity: Notice
Message: Trying to access array offset on value of type null
Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
Line Number: 24
Backtrace:
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
Line: 24
Function: _error_handler
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b3d136f97_11902452
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 384
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
Line: 41
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b3d14aa11_83151422
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
Line: 43
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b47775ef5_14228348
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
Line: 397
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 248
Function: callBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 184
Function: callBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 186
Function: process
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 156
Function: process
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
Line: 88
Function: instanceBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b3cb92fa0_94546305
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 116
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
Line: 71
Function: endChild
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_67089277b12ce9_02546255
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
Line: 238
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
Line: 116
Function: _execute
File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
Line: 45
Function: fetch
File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
Line: 32
Function: view
File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
Line: 292
Function: require_once
A PHP Error was encountered
Severity: Notice
Message: Trying to access array offset on value of type null
Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
Line Number: 29
Backtrace:
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
Line: 29
Function: _error_handler
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b3d136f97_11902452
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 384
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
Line: 41
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b3d14aa11_83151422
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
Line: 43
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b47775ef5_14228348
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
Line: 397
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 248
Function: callBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 184
Function: callBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 186
Function: process
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 156
Function: process
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
Line: 88
Function: instanceBlock
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b3cb92fa0_94546305
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
Line: 116
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
Line: 71
Function: endChild
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_67089277b12ce9_02546255
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
Line: 238
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
Line: 116
Function: _execute
File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
Line: 45
Function: fetch
File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
Line: 32
Function: view
File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
Line: 292
Function: require_once
A PHP Error was encountered
Severity: Notice
Message: Undefined offset: 2
Filename: smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
Line Number: 41
Backtrace:
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
Line: 41
Function: _error_handler
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b3d14aa11_83151422
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 386
Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
Line: 43
Function: _subTemplateRender
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
Line: 123
Function: content_66f26b47775ef5_14228348
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
Line: 114
Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 217
Function: render
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Backtrace:
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Function: _error_handler
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Function: content_66f26b3d136f97_11902452
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Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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Function: render
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Function: getRenderedTemplateCode
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Function: render
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Function: render
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Function: callBlock
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Function: callBlock
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File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
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Function: getRenderedTemplateCode
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Function: getRenderedTemplateCode
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Function: _execute
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Line Number: 29
Backtrace:
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
Line: 29
Function: _error_handler
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Function: content_66f26b3d136f97_11902452
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
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Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
Line: 384
Function: render
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Function: _subTemplateRender
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Function: getRenderedTemplateCode
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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Function: render
File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
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Function: _subTemplateRender
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Function: content_66f26b47775ef5_14228348
File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
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Function: getRenderedTemplateCode
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File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
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Function: render
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Function: process
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Function: instanceBlock
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Function: content_66f26b3cb92fa0_94546305
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Function: getRenderedTemplateCode
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Function: getRenderedTemplateCode
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Function: _execute
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Function: fetch
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Line: 32
Function: view
File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
Line: 292
Function: require_once
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