? ? ? CTLA-4??·???a???????a???????????￠???????????????????2?μ?????·?????·???????￡?????????????????￠???????????????????2?????3???????′?3?1?±???????￡Ipilimumab???·???a?????°?????±?????????1?3?±?|?1?????????a?·?￠?μ???μ?????????????±?μ??FDA???o?????????????μ??CTLA-4?μ?￥???1?￡?????¤?????????????′?2???????±?μ???????????′?3?μ???3???1?|?￡???μ?????2?°?????|?????????????μ?????￠?????????????????1???2???????????????￡?¨severe immunotherapy-related adverse events?￡??irAEs?￡?????￡?????1?o???-???ˉ?????′?3???§???μ???′???????????????￠???????????°???a?·?￠?μ???°?????2CTLA-4???????????????1???￥???????????3???￡?????????????±??Ipilimumab?????????3???????????μ??irAEs???￠?????????μ?????????????????ˉTreg?????°???o?????????????°???1???????????????|???￡???a?????????o???μ?????????￠????CTLA-4???????????????1???￥?μ?????·???????o???????????°?μ?????±???·?????￡?????????o?±???·?????????????????￠???????????μ???′???????????￠?????o?￡???????¨?′?3???§???????§???o?????°?????¤???????????±???????￠?????1?2?????o?????·???????????????????1???￥?￡?¨HL32?￡?????·????????CTLA-4?μ???????1?1???o???????￡
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???? ?? ?? ???¨?1?????￠????HL32-Fab?o?????????????????￥CTLA-4?μ?????′?o?????ˉ???§???￥?????1?1?￡?¨?·???±?|????3.05 ???￡???￡?????????￥?????????3???????????μ?￥?????μ??HL32-Fab?·???±?°?′?1???±?????o??????CTLA-4???????????§???¤???????????￡HL32-Fab???·???a???¨?1???3?¤?|???·?￠???????′?μ?????????′CDR3?????1?1???2????CTLA-4???°?|???????2?￡?μ???2???￡?¨strands A???￠G?o??FG loop?￡??????????????????6?????????°?±?????????3???μ???????′?3???¨?????????o?????|???????￥???·???????￡???￠???????°?????±?¨?μ???μ??Ipilimumab?o??CTLA-4???·???a???????￠???????a???1?′???μ?????????￥???·?????′?|?????????′?3?2?????????￡?????????2???μ???????o?????·???????|?·???????·?￠?????￡??????B7???¤???￥?o?????¤???????1???￥?????o???±?-?????2???????￡??HL32???·???a?????o??????CTLA-4???????????§???¤?????μ???????2???μ???????￡???????????o?????????2???¤???????????¤???????1???￥?μ?????????|?????o???￡???μ???????????′?|?????o??B7???¤???￥?±?-?????????o?????o???1?1?????μ?￡?????2?′?????????1???￥???aCTLA-4???¨???????????1???￥???￡???-???￠CTLA-4?μ?????o???-?1?|?????μ???????μ?￡???·???a????CTLA-4???|???°?μ???????3?????????-???·?2?￠?????μ??B7?μ?????????????·?????￡???2???????μ?????1???￥?????o??CTLA-4???????¤???????-???·?2?o???o?μ???2?????????°???????????????????1???￥?2?o???o?????????μ?????·???a???2?????￡???????°?????¤???????????????????????°?·?￠????Ipilimumab???°????????CTLA-4?′???????°?????????2?????°???±?-???|?μ?????-???·???μ???3?￡???2?￠???????????????????￥???μ???￠???????????￡?±???????????????·?￠????HL32???¨?1?????????????????￥?μ?????????????·???3????????CTLA-4???????§?μ?????￠?????￡?????2?±?￡?3??????CTLA-4???????????2?????°???±?-???|???¨?????μ?????-???·???o???????￡???§???￥???§?μ???·?????????????????￠???????????￠???????????3?μ???·?????????o?????￡?????′????CTLA-4?o??HL32?μ???????o?????§???|?????????′?|?????????????????°?±?????2?????1?￡??pH?μ???±?¤???ˉ???????????????°???????￠?????????°?±?????2?????1?μ?????¤???2???·?μ???μ?§?o?????′?????￡???′???????μ???????????2?????????￥???·?????????±?¤?￡??????????HL32????CTLA-4???????¤?μ???????o?????????￥???·???????￡
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?? ?? ?? ?????????????????????°Structure of CTLA-4 complexed with a pH-sensitive cancer immunotherapeutic antibody???±???a???￠?￡??????2020???a11????3????????Cell Discovery?????????·?￠?±?-???￡?±?±???????|?·???′?3???§???o???????????§???§???o?2?????????????????o???????????a?μ?????????·?????￡???±???·?????????????￠???μ???′?????????o???????o?￡???????¨?′?3???§???????§???o?????°?????¤???????????±???a?1?2???????¨???????·???????￡
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?? ?? ?? ?????-???????′?????￡?ohttps://www.nature.com/articles/s41421-020-00202-9
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