Allurar rigakafin ciwon daji, ko oncovaccine, allurar rigakafi Ta kasance wacce ke kula da ciwon daji da ke akwai ko hana ci gaban ciwon daji.[1] Allurar rigakafin da ke kula da cutar kansa da ke akwai an san su da allurar rigakafi ta cutar kansa ko rigakafin antigen. Wasu daga cikin allurar rigakafin suna da "autologous", ana shirya su daga samfurori da aka karɓa daga wanda ya samar da ita, kuma suna da takamaiman wurin ajiyar su.

Allurar rigakafin cutar kansa
vaccine type (en) Fassara
Bayanai
Ƙaramin ɓangare na vaccine (en) Fassara
Vaccine for (en) Fassara Sankara

Wasu masu bincike suna da'awar cewa ƙwayoyin cutar kansa suna tasowa akai-akai kuma tsarin rigakafi (immunosurveillance).[2] ya lalata su; kuma cewa ciwon daji yana samuwa lokacin da tsarin rigakafin ya kasa lalata su.[3]

Wasu nau'ikan ciwon daji, kamar Ciwon daji na mahaifa da ciwon hanta, ƙwayoyin cuta ne ke haifar da su (oncoviruses). Allurar rigakafin gargajiya game da waɗannan ƙwayoyin cuta, kamar allurar rigakafi ta HPV da allurar rigakawa ta hepatitis B, suna hana waɗannan nau'ikan ciwon daji.[4] Sauran cututtukan daji sun kasance har zuwa wani matakin cututtukatattun ƙwayoyin cuta (misali Ciwon daji na ciki da Helicobacter pylori ).[5] Magungunan rigakafin gargajiya na ƙwayoyin cuta masu haifar da ciwon daji (oncobacteria) ba a tattauna su a cikin wannan labarin ba.

Hanyar da ake amfani da ita

gyara sashe

Ɗaya daga cikin hanyoyin yin allurar rigakafin cutar kansa shine raba sunadarai daga sel na ciwon daji da kuma rigakafin marasa lafiya daga waɗannan sunadarai a matsayin antigens, da fatan motsa tsarin rigakafin don kashe sel na cibiyar daji. Ana gudanar da bincike kan allurar rigakafin cutar kansa don maganin nono, huhu, hanji, fata, koda, prostate da sauran cututtukan daji.[6]

Wata hanyar ita ce samar da maganin rigakafi a cikin mai haƙuri ta amfani da ƙwayoyin cuta na oncolytic. An yi amfani da wannan hanyar a cikin maganin Tamilogene laherparepvec, wani bambancin Kwayar cutar herpes simplex da aka tsara don zaɓar maimaitawa a cikin kwayar cutar da kuma bayyana furotin mai motsa jiki GM-CSF. Wannan yana inganta maganin rigakafin ciwon daji ga antigens na ciwon daji da aka saki biyo bayan lysis na kwayar cuta kuma yana ba da allurar rigakafin mai haƙuri.[7]

Hanyar aiki

gyara sashe

Allurar rigakafin cutar kanjamau tana aiki kamar yadda allurar rigakafi ke aiki, ta hanyar horar da tsarin rigakafi don kai farmaki ga sel da ke dauke da antigens a cikin allurar rigakawa. Bambancin shi ne cewa antigens na allurar rigakafin kwayar cuta an samo su ne daga ƙwayoyin cuta ko ƙwayoyin da suka kamu da kwayar cutaa, yayin da antigens na rigakafin antigen na kumburi an samo su daga ƙwayohin ciwon daji. Tunda antigens na ciwon daji sune antigens da aka samu a cikin sel na ciwon kansa amma ba kwayoyin halitta na al'ada ba, allurar rigakafin da ke dauke da antigens na kumburi ya kamata ta horar da tsarin rigakafin don yin amfani da kwayoyin ciwon daji ba sel masu lafiya ba. Magungunan cutar kansa na musamman sun haɗa da peptide daga sunadarai waɗanda ba a yawan samun su a cikin ƙwayoyin halitta na al'ada amma ana kunna su a cikin sel na ciwon daji ko peptides da ke dauke da takamaiman maye gurbin ciwon daji. Kwayoyin gabatar da antigen (APCs) kamar su sel dendritic suna ɗaukar antigens daga allurar rigakafin, suna sarrafa su cikin epitopes, kuma suna gabatar da epitops zuwa T-cell ta hanyar sunadarai na Major Histocompatibility Complex. Idan T-cells sun gane epitope a matsayin baƙo, ana kunna tsarin rigakafin daidaitawa kuma ana niyya ga sel waɗanda ke bayyana antigens.[8]

Rigakafi da magani

gyara sashe

Allurar rigakafin ƙwayoyin cuta yawanci tana aiki ta hanyar hana yaduwar kwayar cutar. Hakazalika, ana iya tsara allurar rigakafin cutar kansa don yin amfani da antigens na yau da kullun kafin cutar kansa ta samo asali idan mutum yana da abubuwan haɗari masu dacewa. Ƙarin aikace-aikacen rigakafi sun haɗa da hana ciwon daji daga ci gaba ko fuskantar metastasis da hana sake dawowa bayan raguwa. Allurar rigakafin warkewa tana mai da hankali kan kashe kumburi da ke akwai. Duk da yake an nuna allurar rigakafin cutar kansa gabaɗaya tana da aminci, ingancin su har yanzu yana buƙatar ingantawa. Ɗaya daga cikin hanyoyin da za a iya inganta maganin rigakafin shine ta hanyar hada allurar rigakafin tare da wasu nau'ikan rigakafin rigakafi da nufin motsa tsarin rigakafin. Tun da ciwon daji sau da yawa yana haifar da hanyoyin da za su iya hana tsarin rigakafi, toshewar rigakafin kwanan nan ya sami kulawa mai yawa a matsayin magani mai yuwuwa da za a haɗa shi da allurar rigakafi. Don allurar rigakafi, hanyoyin da aka haɗu da su na iya zama mafi tsanani, amma ana buƙatar kulawa mafi girma don tabbatar da amincin marasa lafiya masu lafiya don haɗuwa da rigakafin rigakafi.[9]

Allurar rigakafin cutar kansa na iya zama tushen tantanin halitta, furotin- ko peptide-tushen, ko tushen kwayar halitta (DNA / RNA).[9]

Allurar rigakafin ƙwayoyin halitta sun haɗa da ƙwayoyin ƙwayoyin cuta ko ƙwayoyin ƙwayar cuta. Ana hasashen ƙwayoyin ciwon daji daga mai haƙuri su ƙunshi mafi girman bakan antigen masu dacewa, amma wannan hanyar tana da tsada kuma sau da yawa tana buƙatar ƙwayoyin ƙwayoyin cuta da yawa daga mai haƙƙin don su kasance masu tasiri.[10] Yin amfani da haɗin ƙwayoyin cutar kansa da suka yi kama da ciwon daji na mai haƙuri na iya shawo kan waɗannan shingen, amma wannan hanyar ba ta da tasiri. Canvaxin, wanda ya haɗa da layin sel na melanoma guda uku, ya gaza gwajin asibiti na III.[10] Wani dabarun rigakafin da ke tattare da kwayoyin halitta ya haɗa da sel dendritic na autologous (dendritic cells da aka samo daga mai haƙuri) wanda aka kara antigen na kumburi. A cikin wannan dabarar, ƙwayoyin dendritic da ke gabatar da antigen kai tsaye suna motsa T-cell maimakon dogaro da sarrafa antigens ta hanyar APCs na asali bayan an kawo allurar rigakafin. Magungunan rigakafin dendritic da aka fi sani da shi shine Sipuleucel-T (Provenge), wanda kawai ya inganta rayuwa da watanni huɗu. Ingancin allurar rigakafin dendritic cell na iya iyakancewa saboda wahalar samun sel su yi ƙaura zuwa lymph nodes kuma su yi hulɗa tare da T-cell.[9]

Allurar rigakafin da ke tattare da Peptide yawanci sun kunshi takamaiman epitopes na ciwon daji kuma galibi suna buƙatar adjuvant (alal misali, GM-CSF) don motsa tsarin rigakafi da haɓaka antigenicity.[8] Misalan waɗannan epitopes sun haɗa da Her2 peptides, kamar GP2 da NeuVax. Koyaya, wannan tsarin yana buƙatar bayanin MHC na mai haƙuri saboda Ƙuntatawar MHC.[11] Ana iya shawo kan buƙatar zaɓin bayanan MHC ta hanyar amfani da peptides masu tsawo ("gidan peptides masu tsayi") ko furotin mai tsabta, wanda APCs ke sarrafawa cikin epitopes.[11]

Allurar rigakafin da ke tattare da kwayoyin halitta sun hada da nucleic acid (DNA / RNA) wanda ke ƙunshe da kwayar halitta. Ana bayyana kwayar halitta a cikin APCs kuma ana sarrafa samfurin furotin a cikin epitopes. Bayar da kwayar halitta yana da ƙalubale musamman ga wannan nau'in allurar rigakafi.[9] Akalla dan takarar magani guda ɗaya, mRNA-4157/V940, yana binciken sabbin Allurar rigakafin mRNA don amfani a cikin wannan aikace-aikacen.[12][13]

Gidan yanar gizon clinicaltrials.gov ya lissafa gwaje-gwaje sama da 1900 da ke da alaƙa da kalmar "allurar rigakafin cutar kansa". Daga cikin wadannan, 186 sune gwaje-gwaje na Mataki na 3.  [yaushe?][<span title="The time period mentioned near this tag is ambiguous. (January 2024)">when?</span>]

  • A cikin gwajin Mataki na III na follicular lymphoma (wani nau'in lymphoma wanda ba Hodgkin ba), masu bincike sun ba da rahoton cewa BiovaxID (a matsakaici) ya tsawaita warkewa da watanni 44.2, tare da watanni 30.6 don sarrafawa.[14]
  • A ranar 14 ga Afrilu, 2009, Kamfanin Dendreon ya ba da sanarwar cewa gwajin asibiti na Phase III na sipuleucel-T, allurar rigakafin cutar kansa da aka tsara don magance cutar kansa ta prostate, ya nuna karuwar rayuwa. Ya sami amincewar Hukumar Abinci da Magunguna ta Amurka (FDA) don amfani da shi a cikin maganin marasa lafiya na ciwon daji a ranar 29 ga Afrilu, 2010.[15][16]
  • Sakamakon wucin gadi daga gwajin mataki na III na Tamilogene laherparepvec a cikin melanoma ya nuna gagarumin martani na kumburi idan aka kwatanta da gudanar da GM-CSF kadai.[7]
  • Wani bita na Trial Watch na baya-bayan nan (2015) na allurar rigakafin peptide ya taƙaita sakamakon gwaje-gwaje sama da 60 da aka buga a cikin watanni 13 da suka gabata.[11] Wadannan gwaje-gwaje sun yi niyya da cututtukan jini (kansar jini), melanoma (kansar fata), ciwon nono, ciwon daji na kai da wuyansa, ciwon kansa na gastroesophageal, ciwon huhu, ciwon hanta, ciwon prostate, ciwon nono na ovarian, da ciwon daji. Antigen sun hada da peptides daga HER2, telomerase (TERT), survivin (BIRC5), da kuma Wilms' tumor 1 (WT1). Gwaje-gwaje da yawa sun yi amfani da cakuda "na mutum" na 12-15 daban-daban peptides. Wato, suna dauke da cakuda peptides daga ciwon mai haƙuri wanda mai haƙuri ke nuna amsawar rigakafi. Sakamakon waɗannan binciken sun nuna cewa waɗannan allurar rigakafin peptide suna da ƙananan sakamako masu illa kuma suna ba da shawarar cewa suna haifar da martani na rigakafi a cikin marasa lafiya da aka kula da su tare da allurar rigakawa. Labarin ya kuma tattauna gwaje-gwaje na asibiti 19 da aka fara a lokaci guda. Wadannan gwaje-gwaje suna da niyya ga kumburi mai ƙarfi, glioma, glioblastoma, melanoma, da nono, cervical, ovarian, colorectal, da kuma wadanda ba karamin ciwon daji na huhu ba kuma sun haɗa da antigens daga MUC1, IDO1 (Indoleamine 2,3-dioxygenase), CTAG1B, da masu FARKAR VEGF guda biyu, FLT1 da KDR. Musamman, ana gwada allurar rigakafin IDO1 a cikin marasa lafiya tare da melanoma a hade tare da mai hana rigakafin rigakafi ipilimumab da mai hana BRAF (gene) venurafenib.

Tebur mai zuwa, taƙaita bayanai daga wani bita na baya-bayan nan yana nuna misali na antigen da aka yi amfani da shi a cikin allurar rigakafin da aka gwada a cikin gwajin asibiti na Phase 1/2 don kowane ɗayan cututtukan daji 10 daban-daban:[10]

Nau'in cutar kansa Antigen
Ciwon daji NY-ESO-1
Ciwon nono HER2
Ciwon daji na mahaifa HPV16 E7 (Papillomaviridae#E7)
Ciwon daji na launi CEA (Carcinoembryonic antigen)
Leukemia WT1
Melanoma MART-1, gp100, da tyrosinase
Ciwon daji na huhu (NSCLC) URLC10, VEGFR1, da VEGFR2
Ciwon daji na ovary wanda ya tsira
Ciwon daji na hanta MUC1
Ciwon daji na prostate MUC2

Oncovaccines da aka amince da su

gyara sashe

Oncophage was approved in Russia in 2008 for kidney cancer. It is marketed by Antigenics Inc.[ana buƙatar hujja]

Sipuleucel-T, Provenge, FDA ta amince da shi a watan Afrilu na shekara ta 2010 don ciwon daji na hormone-refractory prostate. Dendreon Corp ce ke tallata shi.

An amince da CimaVax-EGF a Cuba a cikin 2011.[17] Kamar Oncophage, har yanzu ba a amince da shi ba don amfani a Amurka, kodayake an riga an yi gwajin mataki na II har zuwa wannan ƙarshen.[18][19]

Bacillus Calmette-Guérin (BCG) an amince da shi ta FDA a cikin 1990 a matsayin allurar rigakafi don ciwon daji na farko.[20] Ana iya gudanar da BCG a cikin intravesically (kai tsaye a cikin kumburi) ko kuma a matsayin mai taimakawa a wasu allurar rigakafin cutar kansa.

Binciken da aka watsar

gyara sashe

CancerVax (Canvaxin), Genitope Corp (MyVax keɓance immunotherapy), da FavId FavId (Favrille Inc) misalai ne na ayyukan rigakafin cutar kansa waɗanda aka dakatar, saboda sakamakon mummunan mataki na III da IV.  [ana buƙatar hujja]

Halaye masu kyau

gyara sashe

Allurar rigakafin cutar kansa tana neman yin amfani da takamaiman antigen na ciwon daji kamar yadda ya bambanta da furotin na kai. Zaɓin mai ba da taimako mai dacewa don kunna ƙwayoyin antigen-presenting don motsa martani na rigakafi, ana buƙatar. Bacillus Calmette-Guérin, gishiri na aluminum, da squalene-mai-ruwa emulsion an amince da su don amfani da asibiti. Ya kamata allurar rigakafi mai inganci ta motsa ƙwaƙwalwar ƙwaƙwalwa ta dogon lokaci don hana sake dawowar kumburi. Wasu masana kimiyya suna da'awar cewa dole ne a kunna tsarin rigakafin da aka haifa don cimma cikakkiyar kawar da kumburi.[21]

'Yan takarar antigen

gyara sashe

An raba Antigen na ciwon daji zuwa kashi biyu: antigens na kumburi; da kuma antigens na musamman na kumburi. Ana nuna antigens da aka raba ta hanyar kumburi da yawa. Antigen na musamman na ciwon daji ya samo asali ne daga maye gurbin da aka haifar ta hanyar cututtukan jiki ko sinadarai; saboda haka ana bayyana su ne kawai ta hanyar ciwon daji.

A cikin wata hanyar, allurar rigakafi tana dauke da ƙwayoyin ƙwayoyin cuta gaba ɗaya, kodayake waɗannan allurar rigakawa ba su da tasiri sosai wajen haifar da martani na rigakafi a cikin samfuran ciwon daji na kai tsaye. An bayyana antigen na kumburi yana rage haɗarin rigakafin jiki, amma saboda amsawar rigakafin ana jagoranta zuwa epitope guda ɗaya, kumburi na iya guje wa lalacewa ta hanyar bambancin asarar antigen. Tsarin da ake kira "yaduwar epitope" ko "tsarin rigakafi" na iya rage wannan rauni, kamar yadda wani lokacin amsawar rigakafi ga antigen guda ɗaya na iya haifar da rigakafi akan wasu antigens a kan wannan kumburi.[21]

Misali, tunda Hsp70 yana taka muhimmiyar rawa wajen gabatar da antigens na kwayoyin da aka lalata ciki har da sel na ciwon daji,[22] ana iya amfani da wannan furotin a matsayin mai taimakawa mai tasiri a ci gaban allurar rigakafin cutar kansa.[23]

Matsalolin da ake tsammani

gyara sashe

Allurar rigakafi ga wani kwayar cuta tana da sauƙin ƙirƙirar. Kwayar cutar baƙo ce ga jiki, sabili da haka tana nuna antigens wanda Tsarin rigakafi zai iya ganewa. Bugu da ƙari, ƙwayoyin cuta yawanci suna ba da 'yan bambance-bambance masu inganci. Sabanin haka, samar da allurar rigakafin ƙwayoyin cuta waɗanda ke canzawa koyaushe kamar mura ko HIV ya kasance matsala. Ciwon daji na iya samun nau'ikan sel da yawa, kowannensu yana da antigens daban-daban. Wadannan kwayoyin an samo su ne daga kowane mai haƙuri kuma suna nuna kaɗan idan akwai antigens waɗanda baƙi ne ga wannan mutumin. Wannan ya sa ya zama da wahala ga tsarin rigakafi don rarrabe ƙwayoyin cutar kansa daga ƙwayoyin halitta na yau da kullun. Wasu masana kimiyya sun yi imanin cewa Ciwon daji na koda da melanoma sune cututtukan daji guda biyu tare da mafi yawan shaidu na amsawar rigakafi, watakila saboda sau da yawa suna nuna antigens waɗanda aka kimanta a matsayin baƙi. Yawancin ƙoƙari na samar da allurar rigakafin cutar kansa ana jagoranta su akan waɗannan kumburi. Koyaya, nasarar Provenge a cikin ciwon daji na prostate, cuta da ba ta sake dawowa ba, tana nuna cewa cututtukan daji ban da melanoma da ciwon daji da koda na iya zama daidai da haɗari ga cutar rigakafi.  [ana buƙatar hujja]

Koyaya, yawancin gwaje-gwajen rigakafin asibiti sun gaza ko kuma sun sami sakamako mai sauƙi bisa ga ƙa'idodin RECIST.[24] Ba a san ainihin dalilan ba, amma yiwuwar bayani sun hada da:

  • Mataki na cututtukan da suka fi ci gaba: manyan abubuwan da ke cikin ciwon daji suna hana tsarin rigakafi ta hanyar amfani da hanyoyin kamar ɓoye cytokines wanda ke hana aikin rigakafi. Mataki mafi dacewa don allurar rigakafin ciwon daji mai yiwuwa ya kasance da wuri, lokacin da ƙarancin kumburi ya yi ƙasa, wanda ke rikitar da tsarin gwaji, wanda ke ɗaukar sama da shekaru biyar kuma yana buƙatar marasa lafiya da yawa su kai maki masu auna. Ɗaya daga cikin madadin shine ya yi niyya ga marasa lafiya tare da cututtukan da suka rage bayan tiyata, radiotherapy ko chemotherapy wanda ba ya cutar da tsarin rigakafi.
  • Bambance-bambance na asarar tserewa (wanda ke da niyya ga antigen guda ɗaya) na iya zama ƙasa da tasiri. Ciwon daji ba daidai ba ne kuma bayyanar antigen ta bambanta sosai tsakanin ciwon daji (har ma a cikin mai haƙuri ɗaya). Magungunan rigakafin da suka fi tasiri na iya haɓaka amsawar rigakafi game da nau'ikan antigen na kumburi don rage damar maye gurbin kumburi kuma ya zama mai tsayayya da maganin.
  • Magunguna da suka gabata na iya canza ciwon daji ta hanyoyin da ke soke allurar rigakafin. (Jarabawar asibiti da yawa sun kula da marasa lafiya bayan chemotherapy wanda zai iya lalata tsarin rigakafi. Marasa lafiya waɗanda aka hana rigakafi ba masu kyau ba ne ga allurar rigakafi.)
  • Wasu ciwon daji suna ci gaba da sauri kuma / ko ba zato ba tsammani, kuma suna iya wuce tsarin rigakafi. Ci gaba da amsawar rigakafi ga rigakafin rigakafi na iya buƙatar watanni, amma wasu cututtukan daji (misali ci gaban hanta) na iya kashe marasa lafiya a cikin ɗan gajeren lokaci.
  • Yawancin gwaje-gwaje na rigakafin cutar kansa suna da niyyar amsawar rigakafin marasa lafiya. Haɗin kai yawanci yana nuna cewa marasa lafiya tare da amsawar rigakafi mafi ƙarfi sun rayu mafi tsawo, suna ba da shaida cewa allurar rigakafin tana aiki. Wani madadin bayani shine cewa marasa lafiya tare da mafi kyawun maganin rigakafi sun kasance marasa lafiya tare le mafi kyawun hangen nesa, kuma da sun tsira mafi tsawo ko da ba tare da allurar rigakafi ba.

Shawarwari

gyara sashe

A watan Janairun shekara ta 2009, wani bita ya ba da shawarwari don ci gaban oncovaccine mai nasara kamar haka:[25]

  • Saitin da aka yi niyya tare da ƙananan nauyin cutar.
  • Gudanar da gwaje-gwaje na Mataki na II don shirin Mataki na III ya isa ya sami isasshen ƙarfi.
  • Kada ku yi amfani da antigen tare da adjuvant tare da adyuvant kadai. Manufar ita ce ta kafa fa'idar asibiti na rigakafin rigakafi (watau, allurar rigakafi) akan ma'aunin kulawa. Adjuvant na iya samun sakamako na asibiti mai ƙarancin matakin da ke karkatar da gwajin, yana ƙara damar yin mummunar ƙarya.
  • Shawarwarin ci gaba na asali akan bayanan asibiti maimakon martani na rigakafi. Abubuwan ƙarshe na lokaci zuwa taron sun fi mahimmanci kuma sun dace da asibiti.
  • Tsarin tsarawa a cikin shirin tun daga farkon; saka hannun jari a masana'antu da gwajin samfurin da wuri.

Dubi kuma

gyara sashe
  • Magungunan rigakafi
  • Magungunan rigakafin cutar kansa
    • Abubuwan guba na Coley
  • Chemoprophylaxis
  • Allurar rigakafin HPV
  • Allurar rigakafin magani
  • Allurar rigakafin cutar kansa da aka yi niyya da CD4+ T cells
  • Magungunan rigakafin cutar kansa na mRNA

Haɗin waje

gyara sashe

Manazarta

gyara sashe
  1. Kwok M, Fritsch EF, Wu CJ (January 2021). "Cancer and COVID-19: On the Quest for Effective Vaccines". Blood Cancer Discovery. 2 (1): 13–18. doi:10.1158/2643-3230.BCD-20-0205. PMC 8500734 Check |pmc= value (help). PMID 34661150 Check |pmid= value (help).
  2. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (April 2001). "IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity". Nature. 410 (6832): 1107–1111. Bibcode:2001Natur.410.1107S. doi:10.1038/35074122. PMID 11323675. S2CID 205016599.
  3. Dunn GP, Old LJ, Schreiber RD (2004). "The three Es of cancer immunoediting". Annual Review of Immunology. 22 (i): 329–360. doi:10.1146/annurev.immunol.22.012703.104803. PMID 15032581.
  4. Babu RA, Kumar KK, Reddy GS, Anuradha C (2010). "Cancer Vaccine : A Review". Journal of Orofacial Sciences. 2 (3): 77–82. doi:10.4103/0975-8844.103507 (inactive 24 April 2024). S2CID 68256825.CS1 maint: DOI inactive as of ga Afirilu, 2024 (link)
  5. "Oral vaccine could fight source of stomach cancers". Vaccine News Reports. Archived from the original on 2015-04-24. Retrieved 2010-06-22.
  6. Giarelli E (October 2007). "Cancer vaccines: a new frontier in prevention and treatment". Oncology. 21 (11 Suppl Nurse Ed): 11–7, discussion 18. PMID 18154203.
  7. 7.0 7.1 Amgen press release. Amgen announces top-line results of phase 3 talimogene laherparepvec trial in melanoma. Mar 19, 2013. Available here Archived 21 ga Janairu, 2014 at the Wayback Machine
  8. 8.0 8.1 Sayour EJ, Mitchell DA (2017-02-06). "Manipulation of Innate and Adaptive Immunity through Cancer Vaccines". Journal of Immunology Research. 2017: 3145742. doi:10.1155/2017/3145742. PMC 5317152. PMID 28265580.
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