Nzira Itsva Yekudzivirira Zvakakomba Zvakaipa zveCancer Immune Therapies

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Nyanzvi kuCincinnati Chirevo cheVana, mumakonzo, kuti kurapwa kweantibody kunogona kuvandudza kupona kana imwe mhando ye 'cytokine dutu' yarova.

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Zvingave vana vari kurarama nezvirwere zvisingawanzo kudzivirirwa nezvirwere zvemuviri kana varwere vegomarara vari kutsvaga kurapwa kutsva kwekudzivirira muviri, vanhu vazhinji vari kudzidza nezve nzira inouraya ye immune system yakawandisa inonzi "cytokine dutu."              

Vanachiremba uye masayendisiti akaziva nezve cytokine dutu kwenguva yakareba vanoziva zvakare kuti zvinhu zvakawanda zvinogona kubatanidzwa mukuzvikonzeresa, uye kurapwa kushoma chete kunogona kudzinonotsa. Ikozvino, timu kubva kuCincinnati Vana inoshuma budiriro yepakutanga-tanga pakudzora mamwe madutu ecytokine nekukanganisa masaini anobva mumaseru akaiswa T mumasoja emuviri wedu. 

Zvakawanda zvakawanikwa zvakaburitswa Ndira 21, 2022, muScience Immunology. Chidzidzo ichi chine vanyori vatatu vanotungamira: Margaret McDaniel, Aakanksha Jain, naAmanpreet Singh Chawla, PhD, vese vaimbove neCincinnati Vana. Munyori mukuru anowirirana aive Chandrashekhar Pasare, DVM, PhD, Purofesa, Chikamu cheImmunobiology uye Co-Director weCentre for Inflammation and Tolerance paCincinnati Vana.

"Kuwanikwa uku kwakakosha nekuti takaratidza, mumakonzo, kuti nzira dzekuzvimba dzinopinda murudzi urwu rweT cell-driven cytokine dutu dzinogona kudzikiswa," anodaro Pasare. "Rimwe basa richadikanwa kuratidza kuti nzira yatakashandisa mumakonzo inogonawo kuve yakachengeteka uye inoshanda kuvanhu. Asi ikozvino tine chinangwa chakajeka chekutevera. "

Chii chinonzi cytokine dutu?

Cytokines mapuroteni madiki akavanzwa nechero rudzi rwesero. Mazana ema cytokine anozivikanwa anoita mhatsa yemabasa akakosha, akajairika. Mune immune system, ma cytokines anobatsira kutungamira T-masero uye mamwe maseru edziviriro kurwisa nekubvisa mavhairasi anopinda uye mabhakitiriya pamwe nekurwisa cancer.

Asi dzimwe nguva, “dutu” re<em>cytokine rinobva pakuva nemasero eT akawandisa muhondo. Mhedzisiro yacho inogona kuve yakanyanya kuzvimba iyo inogona kukonzera zvakanyanya, kunyangwe kukuvara kunouraya kune hutano tishu.

Tsvagiridzo nyowani inovhenekera nzira yekusaina padanho rema molecular. Chikwata chinoshuma kuti dzinenge mbiri dzakazvimiririra nzira dziripo dzinokonzeresa kuzvimba mumuviri. Kunyange paine nzira inozivikanwa uye yakagadzwa yekuzvimba yekuita kune vapambi vekunze, basa iri rinotsanangura nzira isinganzwisisike iyo inotyaira "isina hutachiona" kana isina hutachiona-ine chekuita nekudzivirira kwemuviri.

Nhau dzine tariro yekuchengetwa kwegomarara

Zviviri zvezvinonyanya kufadza kenza kukura mumakore achangopfuura kwave kuvandudzwa kwecheckpoint inhibitors uye chimeric antigen receptor T cell therapy (CAR-T). Nzira dzekurapa idzi dzinobatsira masero eT kuona uye kuparadza masero egomarara ayo aimbonzvenga dziviriro dzemuviri.

Mishonga yakati wandei yakavakirwa paCAR-T tekinoroji inotenderwa kurapa patents kurwisa diffuse hombe B-cell lymphoma (DLBCL), follicular lymphoma, mantle cell lymphoma, multiple myeloma, uye B-cell acute lymphoblastic leukemia (ALL). Zvichakadaro. akati wandei ekutarisa inhibitors ari kubatsira vanhu vane gomarara remapapu, gomarara repazamu uye mamwe magomarara akati wandei. Mishonga iyi inosanganisira atezolizumab (Tecentriq), avelumab (Bavencio), cemiplimab (Libtayo), dostarlimab (Jemperli), durvalumab (Imfinzi), ipilimumab (Yervoy), nivolumab (Opdivo), uye pembrolizumab (Keytruda).

Nekudaro, kune vamwe varwere, marapirwo aya anogona kubvumira mapoka ehutsotsi T-sero kurwisa matishu ane hutano pamwe negomarara. Munhevedzano yembeva uye kuyedza murabhoritari, timu yekutsvagisa kuCincinnati Vana inoshuma ichironda kwaibva kuzvimba kunokonzerwa nekusazvibata kweT cell iyi uye inoratidza nzira yekuzvidzivirira.

"Takawona yakakosha siginecha node inoshandiswa neeffector memory T masero (TEM) kuunganidza yakafara proinflammatory chirongwa mu innate immune system," Pasare anodaro. "Takaona kuti cytokine toxicity uye autoimmune pathology inogona kununurwa zvizere mumhando dzakawanda dzeT cell-inotyairwa kuzvimba nekukanganisa masaini aya kungave kuburikidza nekugadzirisa majini kana nediki mamorekuru."

Pasina kurapwa, 100 muzana yemakonzo akafurirwa kusangana nedutu recytokine senge rakakonzerwa neCAR-T kurapwa akafa mukati memazuva mashanu. Asi 80 muzana yemakonzo aibatwa nemasoja ekudzivirira chirwere anovharisa masaini aibva mumasero eT akaiswa akararama mazuva manomwe.

Kuwanikwa hakushande kuCOVID-19

Vanhu vazhinji vane hutachiona hwakanyanya kubva kuSARS-CoV-2 hutachiona vakatamburawo nemadutu ecytokine. Nekudaro, pane mutsauko wakakosha pakati pe systemic kuzvimba kunokonzerwa nehutachiona hwehutachiona uye iyi "isina hutachiona" fomu yekutiza kuzvimba kunokonzerwa neakabatidzwa T masero.

"Takacherechedza boka remajeni anonyanya kukonzerwa neTEM masero asingabatanidzi muhutachiona hwehutachiona kana bhakitiriya," anodaro Pasare. "Izvi zvinoreva kushanduka kwakasiyana kwemaitiro maviri aya ekuita zvemukati."

Matanho anotevera

Mune dzidziso, kurapwa kweantibody kwakafanana nekushandiswa muzvidzidzo zvegonzo kunogona kupihwa varwere vegomarara vasati vawana kurapwa kweCAR-T. Asi kutsvagisa kwakawanda kunodiwa kuona kana nzira yakadai yakachengeteka zvakakwana kuti iedzwe mumakiriniki evanhu.

Pamusoro pekugadzira nzira inovimbisa yegomarara rinowanikwa nevanhu vakawanda, kudzora nzira iyi yekuzvimba isina utachiona inogona kubatsira kuvana vanozvarwa vaine chimwe chezvirwere zvitatu zvisingawanikwe zvakanyanya neautoimmune, kusanganisira IPEX syndrome, iyo inokonzerwa nekushanduka kwegene reFOXP3; CHAI chirwere, chinokonzerwa nekusashanda kweiyo CTLA-4 gene; uye chirwere cheLATIAE, chinokonzerwa nekuchinja muLRBA gene. 

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Mupepeti mukuru we eTurboNew ndiLinda Hohnholz. Iye anogara muTN HQ muHonolulu, Hawaii.

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