×ðÁú¿­Ê±

DSPE-PEG2000-MAL£º¸³ÄÜin vivo CAR-TµÝË͵ÄÐÂ×¥ÊÖ

2025-11-04

×ÖºÅ

¡¡¡¡CAR-TÁÆ·¨ÊÇÈËÀàÔÚÉúÎïÒ½Ò©ÁìÓò¼ÌС·Ö×Ó¡¢´ó·Ö×ÓÒÔºó  £¬ÔÚϸ°û²ãÃæÈ¡µÃµÄÓÖÒ»´Î¸ïÃüÐÔÍ»ÆÆ¡£ÌåÍâCAR-T(ex vivo CAR-T)ÒÑÔÚBϸ°û°×Ѫ²¡ºÍÁܰÍÁö´´ÏÂÁËѤÀõÄÀï³Ì±®  £¬µ«ÆäÖØ´óµÄÖÆÔìÀú³Ì¡¢¸ß°ºµÄÓöȼ°¶¾ÐԵȾÖÏÞ³ÉΪÁËÕâÏîÊÖÒÕ´óÃæ»ýÆÕ¼°µÄÆ¿¾±ËùÔÚ¡£¶øÌåÄÚCART(in vivo CAR-T)ÔòÒÔÇ㸲ÐÔµÄÊÖÒÕ  £¬Í¨¹ýÌØÊâÔØÌ彫CAR»ùÒòÖ±½ÓËÍÈëÌåÄÚ  £¬Ìø¹ý·±ËöµÄÌåÍâ°ì·¨  £¬Ö±½ÓÔÚ»¼ÕßÌåÄÚÍê³É¶ÔTϸ°ûµÄ“×°±¸Éý¼¶”  £¬³ÉΪÏÂÒ»´úϸ°ûÃâÒßÖÎÁÆµÄÆÆ¾Öµã¡£

¡¡¡¡2025Äê6ÔÂ11ÈÕ  £¬ÔËÓÃLNPΪÖ÷ÒªµÝËÍÔØÌåµÄin vivo CAR-TÁÆ·¨¹«Ë¾CapstanÐû²¼  £¬ÆäÒÔרÓÐÊÖÒÕtLNP(ÌåÄÚ°ÐÏòÖ¬ÖÊÄÉÃ׿ÅÁ£)ÎªÔØÌåµÄin vivo CAR-Tϸ°ûÁÆ·¨CPTX2309Õýʽ×îÏÈ¢ñÆÚÁÙ´²ÊÔÑé  £¬ÓÃÓÚÖÎÁÆBϸ°û½éµ¼µÄ×ÔÉíÃâÒß¼²²¡1¡£Ëæºó  £¬2025Äê6ÔÂ30ÈÕ  £¬°¬²®Î¬ÓëCapstanÐû¹«¸æ¿¢×îÖÕЭÒé  £¬°¬²®Î¬½«ÒÔ21ÒÚÃÀÔªµÄ¼ÛÇ®ÊÕ¹ºCapstan  £¬´Ë´ÎÊÕ¹ºº­¸ÇÆä¸Õ½øÈë¢ñÆÚÁÙ´²ÊÔÑéµÄCPTX23092¡£Í¬Ê±  £¬°¬²®Î¬»¹½«»ñµÃCapstanµÄtLNPƽ̨ÊÖÒÕ  £¬¸ÃÊÖÒÕÖ¼ÔÚµÝËÍRNAÓÐÓÃÔØºÉ(ÈçmRNA)  £¬Äܹ»ÔÚÌåÄÚ¶ÔÌØ¶¨Ï¸°ûÀàÐ;ÙÐй¤³ÌˢС£

¡¡¡¡ÄÉÃ×ÊÖÒյķÉËÙÉú³¤ÎªÒ©ÎïµÝËÍϵͳ´øÀ´Á˸ïÃüÐÔµÄÍ»ÆÆ¡£ÒÔCapstanµÄÊÖÒÕÆ½Ì¨ÎªÀý  £¬ÔÚÖÆ±¸LNPʱ»ìÈëÒÔÂíÀ´õ£Ñǰ·»ùÍÅ(-Maleimide  £¬MAL)µÄPEGÖ¬  £¬´ýLNPÖÆ±¸Íê³Éºó  £¬ÔÙ½«´øÓÐÛÏ»ù(-SH)µÄ¿¹Ìåͨ¹ý·õÓýµÄ·½·¨Å¼ÁªÔÚº¬ÓÐMAL»ùÍŵÄPEGÖ¬ÉÏ  £¬¼´¿É¸¶ÓëLNPϵͳ“×Ô¶¯°ÐÏò”µÄÄÜÁ¦¡£

¡¡¡¡DSPE-PEG2000-MAL(1,2-¶þÓ²Ö¬õ£-sn-¸ÊÓÍ-3-Á×ËáÒÒ´¼°·-¾ÛÒÒ¶þ´¼2000-ÂíÀ´õ£Ñǰ·)×÷ΪһÖÖÉè¼Æ¾«ÇɵĹ¦Ð§»¯Á×Ö¬-PEGÑÜÉúÎï  £¬ÒѳÉΪ¹¹½¨ÏȽøÄ˽×ÔØÌåµÄÖ÷ÒªÁ¢ÒìÖÊÁÏÖ®Ò»¡£ÆäÆæÒìµÄ·Ö×ӽṹ¸¶ÓëÁËÔØÌ峤ѭ»·¡¢×Ô¶¯°ÐÏò¼°¶à¹¦Ð§¼¯³É»¯µÄÄÜÁ¦  £¬ÔÚ°ÐÏòÖÎÁÆ¡¢·Ö×ÓÓ°ÏñºÍÃâÒßÁÆ·¨µÈÁìÓòÕ¹ÏÖ³öÖØ´óµÄÓ¦ÓÃDZÁ¦¡£

¡¡¡¡·Ö×ӽṹÓëÀí»¯ÌØÕ÷

¡¡¡¡DSPE-PEG2000-MALµÄ·Ö×ÓÁ¿Ô¼Îª2805–3000Da  £¬Ö÷Òª°üÀ¨Èý¸ö¹¦Ð§Ã÷È·µÄÄ£¿é£º

¡¡¡¡DSPE(1,2-Distearoyl-sn-glycero-3-phosphoethanolamine)Êèˮ궨»ùÍÅ£º×÷ΪÁ½Ç×ÐÔ·Ö×ÓµÄÊèˮβ²¿  £¬DSPEº¬ÓÐÁ½ÌõC18±¥ºÍÖ¬·¾ËáÁ´  £¬Æä½á¹¹Óëϸ°ûĤÁ×֬˫·Ö×Ó²ã¾ßÓи߶ÈÇ׺ÍÐÔ  £¬Äܹ»Îȹ̵ØÇ¶ÈëÖ¬ÖÊÌåĤ»ò×é³É½ºÊøµÄÊèË®ÄÚºË  £¬ÎªÕû¸ö·Ö×ÓÌṩÀο¿µÄ궨×÷Óá£

¡¡¡¡PEG2000(Polyethyleneglycol)Ç×Ë®Á´¶Î£º·Ö×ÓÁ¿Ô¼Îª2000DaµÄ¾ÛÒÒ¶þ´¼Á´×é³ÉÁË·Ö×ÓµÄÇ×Ë®¹Ú²ã¡£ÔÚÐÄÀíÇéÐÎÖÐ  £¬PEGÁ´Í¨¹ý¿Õ¼äλ×èЧӦºÍË®ÏàÖúÓà  £¬ÔÚÄ˽×ÔØÌåÍâòÐγÉÒ»²ãÖÂÃܵēˮ»¯ÔÆ”  £¬ÓÐÓÃïÔ̭Ѫ½¬ÂѰ׵ÄÎü¸½  £¬´Ó¶ø¹æ±ÜÍø×´ÄÚÆ¤ÏµÍ³µÄ¿ìËÙɨ³ý¡£ÕâÒ»ÌØÕ÷  £¬¼´“ÒþÐÎЧӦ”(Stealth®effect)  £¬ÊÇÑÓÉìÔØÌåÌåÄÚÑ­»·°ëË¥ÆÚµÄÒªº¦¡£

¡¡¡¡MAL(Maleimide)»îÐÔ×îºó»ùÍÅ£ºÂíÀ´õ£Ñǰ·»ùÍÅÊÇ·Ö×ӵķ´Ó¦»îÐÔÖÐÐÄ¡£ËüÄÜÔÚpH6.5-7.2µÄÌõ¼þÏ  £¬ÓëÛÏ»ù(-SH  £¬Áò´¼)±¬·¢¸ßЧ¡¢ÌØÒìÐÔµÄÂõ¿Ë¶û¼Ó³É·´Ó¦  £¬ÐγÉÎȹ̵ÄÁòÃѹ²¼Û¼ü¡£ÕâÒ»»¯Ñ§Ñ¡ÔñÐÔʹÆä³ÉΪÅþÁ¬º¬°ëë×°±Ëá²Ð»ùµÄ°ÐÏòÅäÌå(È翹Ìå¡¢¶àëÄ¡¢ÊÊÅäÌå)µÄÀíÏë“»¯Ñ§×¥ÊÖ”¡£

       

ÏîÄ¿ ÐÎò
Íâ¹Û °×É«»òÀà°×É«À¯×´¹ÌÌå
ÏûÈÚÐÔ ¿ÉÔÚDMSO¡¢ÒÒ´¼¡¢ÎÂË®ÖÐÊèÉ¢»òÏûÈÚ
pHÎȹÌÐÔ pH 6.5-7.2½ÏÎȹ̣¨×èÖ¹MaleimideË®½â£©
Ó¦Óà ֬ÖÊÌåÐÞÊΡ¢ÉúÎïżÁª¡¢°ÐÏòµÝË͵È

       ÔÚʹÓÃDSPE-PEG2000-MALµÄµÝËÍϵͳÖÐ  £¬DSPE¶Ë²åÈëÁ×֬˫·Ö×Ó²ã  £¬PEGÁ´ÑÓÉìÖÁÍⲿˮÏà  £¬ÏÔÖøÌáÉýÁËϵͳµÄÎȹÌÐÔºÍÌåÄÚÑ­»·¶¯Á¦Ñ§¡£ÀýÈç  £¬¾­PEGÐÞÊεÄÖ¬ÖÊÌå(ÈçDoxil®)°ëË¥ÆÚ¿É´ÓÊýСʱÑÓÉìÖÁÔ¼55Сʱ  £¬²¢½èÖúÔöÇ¿ÉøÍ¸ÖÍÁôЧӦÔÚÖ×Áö²¿Î»ÊµÏÖ±»¶¯¸»¼¯3¡£¶øMAL»ùÍÅÄÜÓ뺬ÛÏ»ù(-SH)·Ö×Ó¶¨ÏòżÁªµÄÌØÕ÷  £¬¸¶ÓëÆä“×Ô¶¯°ÐÏò”µÄÄÜÁ¦¡£ÔÚ½ºÊøÏµÍ³ÖÐ  £¬DSPE-PEG2000-MALÒ²¿É×Ô×é×°ÐγɺË-¿Ç½á¹¹  £¬ÊèË®µÄDSPEÄÚºËÓÃÓÚÔöÈÜ×Ïɼ´¼µÈÄÑÈÜÐÔ»¯ÁÆÒ©Îï  £¬¶øPEGÍâ¿ÇºÍMAL¹¦Ð§»¯ÍâòÔòͬÑùÌṩÎȹÌÐÔºÍ×Ô¶¯°ÐÏòµÄDZÁ¦  £¬ÍØÕ¹mRNAÒ©ÎïµÄÓ¦ÓùæÄ£  £¬ÊµÏÖ¸ü¾«×¼µÄϸ°ûÀàÐÍÌØÒìÐÔµÝËÍ¡£

¡¡¡¡DSPE-PEG2000-MALÒÀ¸½Æä“궨-ÒþÐÎ-ÅþÁ¬”ÈýλһÌåµÄ·Ö×ÓÉè¼Æ  £¬ÒѳÉΪ¾«×¼Ò©ÎïµÝËÍÁìÓò²»¿É»òȱµÄ¹¦Ð§ÖÊÁÏ¡£Ëü²»µ«½â¾öÁËÄ˽×ÔØÌåÔÚÌåÄÚµÄÎȹÌÐԺͳ¤Ñ­»·ÎÊÌâ  £¬¸üÖ÷ÒªµÄÊÇ  £¬Í¨¹ýÆä¸ß¶ÈÌØÒìÐԵĻ¯Ñ§Å¼ÁªÄÜÁ¦  £¬ÊµÏÖÁ˶ÔÄ˽×ÔØÌåµÄÍâò¹¦Ð§»¯  £¬´Ó¶ø¸¶ÓëÆä×Ô¶¯°ÐÏò¡¢ÖÇÄÜÏìÓ¦ºÍÕïÁÆÒ»Ì廯µÈ¸ß¼¶¹¦Ð§¡£Ëæ×ŶÔÃâÒßÉúÎïѧ»úÖÆµÄÉîÈë̽Ë÷  £¬DSPE-PEG2000-MAL¼°ÆäÑÜÉúÎォ¼ÌÐø×÷Ϊ¹¹½¨Öش󡢸ßЧ¡¢ÖÇÄÜÄÉÃ×Ò©ÎïϵͳµÄÖ÷Òª»ùʯ֮һ  £¬Îª¹¥¿ËÖØ´ó¼²²¡ÖÎÁÆÖеÄÖÖÖÖÌôÕ½ÌṩǿÓÐÁ¦µÄÊÖÒÕÖ§³Ö  £¬Íƶ¯¾«×¼Ò½ÁÆÂõÏòеĸ߶È¡£

¡¡¡¡×÷ΪרעÓÚÒ©ÎïµÝËÍÊÖÒÕµÄÁ¢ÒìÐÍÆóÒµ  £¬×ðÁú¿­Ê±¿Æ¼¼³Ð¼Ì“ÒÔÖÊÁÏÁ¢ÒìÒýÁìÉúÎïÒ½Ò©Á¢Ò쓵Ä×ÚÖ¼  £¬ÒÀÍÐ×ÔÉíÔÚÒ©ÎïµÝËÍÁìÓòµÄÖÕÄê»ýÀÛÓëÁ¢ÒìÓÅÊÆ  £¬¿ÉΪÄúÌṩÇкÏÑз¢¼°ÖÐÍâÉ걨ÐèÇóµÄDSPE-PEG2000-MAL²úÆ·  £¬²¢ÎªÈ«ÇòÏàÖúͬ°éÔÚºóÐøµÄÑо¿ÓëÓ¦ÓÃÀú³ÌÖÐ  £¬ÌṩÒÔǰÆÚÑз¢µ½ºóÆÚת»¯µÄÈ«Á÷³ÌÖ§³Ö¡£

¡¡¡¡²Î¿¼ÎÄÏ×

¡¡¡¡1 WIRE, B. Capstan Therapeutics Announces Initiation of Phase 1 Trial of Lead In Vivo CAR-T Therapy, CPTX2309, for Treating Autoimmune Disease, <https://www.businesswire.com/news/home/20250611668181/en/Capstan-Therapeutics-Announces-Initiation-of-Phase-1-Trial-of-Lead-In-Vivo-CAR-T-Therapy-CPTX2309-for-Treating-Autoimmune-Disease> (2025).

¡¡¡¡2 AbbVie. AbbVie to Acquire Capstan Therapeutics, Further Strengthening Commitment to Transforming Patient Care in Immunology, <https://news.abbvie.com/2025-06-30-AbbVie-to-Acquire-Capstan-Therapeutics,-Further-Strengthening-Commitment-to-Transforming-Patient-Care-in-Immunology> (2025).

¡¡¡¡3 Gabizon, A. et al. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res 54, 987-992 (1994).

Òªº¦´Ê£º


˿õ¹å?SILKROSEÇ¿ÊÆÈëפÃÀÍÅ&¹«¹²µãÆÀÆ·ÅÆ¹Ý

ÏÂÒ»Ò³

ÏÂÒ»Ò³£º

˿õ¹å?SILKROSEÇ¿ÊÆÈëפÃÀÍÅ&¹«¹²µãÆÀÆ·ÅÆ¹Ý

ÍøÕ¾µØÍ¼