Antibody - mankhwala osokoneza bongo azokambirana ndi njira

Mafala Akutoma ADC

Antibody - conjubates osokoneza bongo (ADCS) akuimira gulu logundika la khansa yopendekerani kuti ipititse patsogolo tanthauzo ndi chemotherapy. Pophatikiza ma antibodies a Monoclonial okhala ndi othandizira a cytotoxic, Adc amapereka mankhwala mwachindunji ndi maselo a khansa, akuchepetsa kuwonongeka kwa minyewa yathanzi. Woyamba kudziwa mu 1980s, Adc asintha mu mankhwala ovomerezeka azachipatala, omwe ali ndi zopereka zovomerezeka, kuphatikiza adcetris vadotin) ndi Kadctuzum emtansine).

Zovala za Adcs

Adcs amapanga zinthu zitatu zotsutsa:

• - Antiody:Antiibody antibody (Mab) omwe amalumikizana ndi chotupa - Antigen (E.g., HET. Mankhwalawa amachititsa kuti antiwor azikhala otsimikiza za maselo a khansa.
• - Linker:Mlangizi wa mankhwala akulumikiza antibody ku kulipira. Kukhazikika kwake kumazindikira ngati mankhwalawa amasulidwa m'magazi a khansa kapena mkati mwa khansa.
• - Kulipira:Mankhwala a cytotoxic (E.g., austins, Maytansnoids) omwe amayambitsa maselo a khansa.

- ADC Linker Chemistry

Linkers ndi chidwi chofuna kusanza adc ndi kufunika. Amagwera m'magulu awiri:

1. Alema

Izi zimatulutsa zolipira mothandizidwa ndi mkati mwa umeracellular:

• - Ph - Otsatsa Omvera:Samalani m'malo a acidic (E.g., Endosomes / Lusosomes). Chitsanzo: Aboma a hydrazone omwe amagwiritsidwa ntchito mu mylotarg® (gemtuzumab ozogamin).
• - Enzyme - Amodzi Omvera:Kutsukidwa ndi mapuloses (E.g., Cathepsin B) kapena phosphatins. Chitsanzo: Ma Vanine hule a Citorrene ku Adcetris®.
• - Glutath - okonda masewerawa:Dalirani pa umeracellular hule kwambiri kuti muchepetse zomangira.

2. - OND - Amodzi

Izi zimafuna kuwonongeka kwathunthu kwa antibosomes ku Lusosomes kuti atulutse zolipira (E.g. ONTE - Amuna a Cleavableble amapereka chitsimikizo chachikulu cha plasma koma kuchepetsa mphamvu.

Tulutsani Malipiro

Limagwirira mankhwala osokoneza bongo amatengera mtundu wa Linker:

1. Alema:

• - Malo acidic:PH - Baykers omvera hydrolyze mu endosomes (PH ~ 5-6).
• - Clezymatic Cleavage:Mapuloteki a lysosomes invepide - otchuka amatsatsa.
• - Kuchepetsa:Mitundu yayikulu ya glutathone mu maselo a khansa imachepetsa zolimba.
• - Zovuta Zakuthandizira:Malipiro otulutsidwa amatha kuyamwa m'maselo oyandikana nawo, koma zopindulitsa pa zotupa zoyakizika koma zowopsa kwa maselo athanzi.

2. ONTSA - Amodziakulu Osiyanasiyana:

• Antibody imasungidwa ku lysosomes, kumasula kulipira (mwachitsanzo, lysine - dm1 ku Kadcyla®).Palibe othamanga, zomwe zingathetsetse vuto - choopsa chandamale.

Zovuta ndi Mayendedwe Amtsogolo

• - Kusankha Kusankha:Antigens ayenera kufotokozedwa kwambiri pazotupa kuti apewe - chandamale / off - chotupa chotupa.
• - Linker Kutsatsa:Kukhazikika kokhazikika ndipo kumasulidwa kwadongosolo kumavuta.
• - IndeKuwongolera mankhwala - Ziphuphu za antibody (Dar) ndi njira zolumikizira (mwachitsanzo, - Katundu wapadera) kuti apititse patsogolo.
• - Zatsopano:Bispecific, Prodrug - Anunso adalandira ndalama, ndi kuphatikiza njira zotchinga zomwe zikuwunikidwa.

Mapeto

Adcs amalimbikitsa kuti agwirizane ndi mankhwala osokoneza bongo a mankhwala ndi kuchitika, kupereka mayankho ogwira mtima kuthana ndi khansa. Monga ma testicnologies ndi mapiritsi osokoneza bongo amalonjeza bwino kwambiri ndi zovuta zoyipa, kusiya udindo wawo monga zipilala zamakono zamakono.

Mawu osakira: ADC Linker, Kumasulidwa kwa chiwindi