Co esponding au ho : J.V.S. CHANDANA
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion Liscense 4.0.
A e iew on cance accines: Cu en de elopmen s and u u e p ospec s
J.V.S. CHANDANA *, J. RENU, E. SWATHI, D. VARSHA and T. RAMARAO
Depa men o Pha macology, CMR College o Pha macy, Medchal, Hyde abad-501401, India.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 21(01), 132-139
Publica ion his o y: Recei ed on 20 No embe 2024; e ised on 29 Decembe 2024; accep ed on 31 Decembe 2024
A icle DOI: h ps://doi.o g/10.30574/wjbphs.2025.21.1.1018
Abs ac
Tumou immuno he apy has made emendous p og ess in he pas decades, wi h nume ous s udies en e ing he
clinical e alua ion. The cance accine is conside ed a p omising he apeu ic s a egy in he immuno he apy o solid
umou s. Cance accines s imula e an i umo immuni y using umou an igens, which can be deli e ed as whole
cells, pep ides, nucleic acids, e c. An ideal cance accine would be able o o e come umou immunosupp ession
and induce bo h humo al and cellula immuni y. The use o cance accines is conside ed a p omising he apeu ic
s a egy in clinical oncology, which is achie ed by s imula ing an i- umou immuni y wi h umou an igens deli e ed
in he o m o cells, pep ides, i uses and nucleic acids. The ideal cance accine has many ad an ages, including low
oxici y, speci ici y, and induc ion o pe sis en immune memo y o o e come umou he e ogenei y and e e se
he immunosupp essi e mic oen i onmen . Cance ea men is done by su ge y,chemo he apy, adia ion he apy.
These ea men s may cu e ea ly-s age cance , bu a e o en ine ec i e in ea ing ad anced o ecu en cance . Basic
and clinical s udies o he umou mic oen i onmen , which consis s o cance cells, s omal cells, and immune
cells, ha e demons a ed he impo an ole o an i umo immuni y in cance de elopmen and p og ession. Cance
immuno he apy has been p oposed as a ou h cance ea men op ion. In pa icula , he clinical applica ion o immune
checkpoin inhibi o s, such as an i-CTLA-4 and an i-PD-1/PD-L1 an ibodies, o a ious ypes o cance ep esen s a
majo ad ance in cance ea men . Indeed, se e al issues emain o be sol ed o imp o e hei clinical e icacy; hese
include low cance cell an igenici y and poo in il a ion and/o accumula ion o immune cells in he cance
mic oen i onmen .
Keywo ds: Cance accine; Tumou an igen; Tumou esis ance; Immuno he apy; Clinical applica ion
1. In oduc ion
Cance accines a e a ype o immuno he apy ha aims o s imula e he body's immune sys em o ecognize and a ack
cance cells. Cance is one o he leading cause o dea h. This is la gely due o has. ha people end o li e longe , wi h
ewe people dying om o he causes such as in ec ious diseases. In 2000, o e 6 million people died om and he e
we e an es ima ed 10 million new cases. Be ween 2000 and cance 2020 he o al numbe o cases o cance is
p edic ed o inc ease by 73% in he de eloping wo ld and by 29% in he de eloped wo ld, la gely as a esul o
demog aphic shi in ge ia ic popula ion'. A epo on he incidence o common cance s in India in 2004 showed i
as a ound 154 housands and 267 housands in males and emales espec i ely Du ing he pas wo decades, da a
on die and cance ha e g ea ly inc eased and his ein o ces he belie ha a subs an ial p opo ion o cance
is po en ially p e en able by nu i ional means. Quan i a i e es ima es o he p e en able p opo ion in Wes e n
coun ies emain app oxima ely 30% o 40%. P esen ly he e is abundan in o ma ion on speci ic aspec s o nu i ion.
The ela ionships be ween speci ic die a y componen s and cance s a e less well es ablished han ha o die and
ca dio ascula disease. This is due o he ac ha he ole o die in he causa ion o cance has always been di icul
o s udy and quan i y pa ly because he die encompasses wide a ie y o oods, die a y adi ions. habi s and
is a complex mix u e o nu ien s and non nu ien s.
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1.1. Backg ound
The ad en o accines has in oduced new oppo uni ies o p e en and ea in ec ious diseases. The ea lies
accine can be aced back o 1796 when Edwa d Jenne ound ha he cowpox accine p o ec s agains smallpox
in ec ion [1]. As he accine de eloped, i was la e in oduced o ea mo e diseases, such as cance s. The ini ial cance
accine based on umou cells and umou lysa es was de eloped in 1980. Scien is s used au ologous umou cells
o ea colo ec al cance [2]. In he ea ly 1990s, he i s human umou an igen melanoma- associa ed an igen
1 was iden i ied [3], which opened a chap e on using umou an igens in cance accines. In 2010, a dend i ic cell-
based accine(Sipuleucel-T) was success ully used o ea p os a e cance , p o ing he iabili y o cance accines and
c ea ing g ea exci emen in he cance accines ield [4]. The ou b eak o COVID-19 has u ged he de elopmen
o accine echnology and b ough cance accines back in o he public ocus. Cance accines mainly use umou -
associa ed an igens (TAAs) and umou -speci ic an igens (TSAs) o ac i a e he pa ien ’s immune sys em. Theo e ically,
he accine could p o oke bo h speci ic cellula immuni y and humo al immune esponse o p e en umou g ow h
and ul ima ely e adica e umou cells [5]. Cu en ly, mos cance accines a e s ill in he s age o p eclinical and
clinical esea ch [6]. Mo e speci ic an igens and accine de elopmen pla o ms need o be de eloped.
2. Mechanism o cance accine umou an igens
An igen selec ion is a key p ocess in cance accine de elopmen . Tumou an igens ecognized by T lymphocy es play
a cen al ole in he e icacy o cance accines [7]An ideal an igen o a cance accine should be highly immunogenic,
clea ly exp essed in all cance cells (bu no in no mal cells), and essen ial o cance cell su i al [8] Humans a e
p ominen examples o o e exp essed umo an igens, such as epide mal g ow h ac o ecep o 2 (HER2) and human
elome e e e se ansc ip ase [9]. Tissue di e en ia ion an igens a e exp essed by umo cells and no mal cells o he
same o igin as he umo cells.
Fo example, p os a e-speci ic an igen (PSA) is exp essed in he p os a e and p os a e cance . Ty osinase is exp essed
by no mal melanocy es and melanoma cells [10]. AAT is adap able and can be used o a a ie y o pa ien s. Ea ly cance
accines mainly ocused on TAAs. Howe e , due o cen al immuni y, hymic ole ance ac i a ion T cell ecogni ion
TAAs o o he sel -an igens may be elimina ed du ing ea men . De elopmen a ec s he e icacy o accines [11].
The e o e, cance accines using TAAs a e con incing enough o "b eak ole ance". Al hough TAAs ha e been o in e es
o many yea s, clinical ials o TAA-based cance accines ha e had limi ed success [12].
Fu he mo e, TAAs a e also exp essed in non-malignan issues, hus inc easing he isk o accine-induced
au oimmune oxici y.TSAs a e a class o p o eins ha a e speci ically exp essed in umo cells. ASDs a e also called
neoan igens. Indi idually speci ic non-sel p o eins, p oduced by mu a ions in umo cells, a e called neo-an igens [13].
Neoan igens a e exp essed only by umo cells ha igge ue umo -speci ic T cell esponses wi h limi ed “o - a ge ”
damage [14].Compa ed o TAAs, neoan igens ha e s onge immunogenici y and highe a ini y o majo
his ocompa ibili y complex (MHC). Mo eo e , i is no subjec o cen al au ho i y. Immune ole ance [15]. The
widesp ead use o nex - gene a ion sequencing echnology allows o iden i y indi idualized neoan igens in a
apid and cos -e ec i e manne . We also de eloped algo i hms o p edic MHC class I binding epi opes, which has
g ea ly acili a ed he disco e y o new po en ial immunogenic epi opes [16]. Cance accines a ge ing neo an igens
ha e become he p ima y goal o accines agains umo s... Recen ly, hey ha e been e alua ed in se e al clinical
ials. Neoan igen accines ha e shown p omising esul s Imp o ed pa ien su i al [17]. Melanoma accines
Neoan igen-like mRNAs a e a classic example, inducing T cell in il a ion and neoan igen-speci ic killing o au ologous
umo cells . The me as a ic e en a e was signi ican ly educed a e accina ion, and he e was a sus ained
p og ession- ee su i al [18]. In addi ion, accina ion wi h neoan igen-loaded DCs could induce TLiu e al. Jou nal o
Hema ology and Oncology.
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Figu e 1 Mechanism o cance accines. Compa ed o pep ide-based accines, nucleic acid-based accines need mo e
p ocessing s eps a e en e ing he body be o e being p esen ed o T cells by DCs. Howe e , DNA and RNA accines
a e be e sui ed o deli e MHC I p esen a ion an igens han pep ide accines. Tumo an igens a e p ocessed by DCs
and anspo ed o he cell su ace o MHC I and MHC II molecules. In e ac ion be ween MHC–pep ide complex–T cell
ecep o (TCR) and cogna e ecep o - ligand pai s ac i a e T cells. Ac i a ed CD4+ T cells induce B cells o di e en ia e
in o plasma cells and memo y B cells. Ac i a ed T cells di e en ia ed in o CD8+ memo y T cells and CD8+ e ec o T
cells. E en ually, e ec o T cells, B cells, an ibodies, and some cy okines kill umo cells di ec ly o indi ec ly
3. Cance accine pla o ms
Cance accines can be classi ied in o ou ca ego ies:
cell-based accines, pep ide-based accines, i us-based accines, and nucleic acid-based accines (Figu e 1) Cell-
based accines a e ini ially he o m o cance accines.Cell- based cance accines a e o en p epa ed om whole
cells o cell agmen s, con aining almos umo an igens, inducing a b oade an igenic immune esponse.DC accine
is an impo an ield o cell-based accines. Pe sonalized cance accines based on DC-based neoan igens ha e
shown p omising an i umo e ec s in clinical ials. Howe e , he de elopmen o DC accines has been limi ed by
he cumbe some p ocess and high cos s. Vi uses a e na u ally immunogenic and hei gene ic ma e ial has been
enginee ed o con ain sequences ha code o umo an igens. Se e al ecombinan i uses, such as adeno i uscan
in ec immune cells as ec o s. Enginee ing i us Vaccines can ep esen umo an igens in la ge quan i ies The
immune sys em p oducean i umo al immuni y.
In addi ion, oncoly ic i uses can also be used as ec o s. In addi ion o deli e ing umou an igens, he i us i sel
can also lyse umou s and elease umou an igens, u he enhancing he e icacy o he accine and c ea ing long-
e m immune memo y. Howe e , he p ocess o p oducing a i al ec o -based accine is complex. Pep ide-based
subuni accines, which include chemical and biosyn he ic p epa a ions o p edic ed known speci ic umou
an igens, induce a obus immune esponse agains a speci ic si e o he umou an igen. Based on pep ides The subuni
o he accine in combina ion wi h adju an s can e ec i ely p o oke a humo al immune esponse sui able o P e
Ven ila ion and ea men o i al in ec ious diseases. HBV and HPV accines o li e and ce ix cance we e p ima y
o pep ide pep ides -based accines. In pa icula , subuni accines based on i us-like pa icles (VLPs), which can
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ac i a e cellula immune esponses, ha e he shown excellen an i umo ac i i y in ecen yea s. Nucleic acid accines
a e a p omising accine pla o m.
4. Cell based cance accines
Cell-based accine can be di ided in o umou cell accine and immune cell accine. Whole umou cell accine is a
ela i ely simple and di ec app oach o umou immuno he apy. Tumou cell accines con ain he ollowing
componen s: Whole umou -associa ed an igens including epi opesCD4+ and CTL helpe cells. Cellula immune
accines Based on he ole o cells in he immune sys em. DCs a e he mos powe ul specialized ag o-indus ial
complexes in he body. In mos cases, DCs a e equi ed o p esen cance an igens du ing accina ion. The e o e,
an e ec i e way o an i umo immuni y is o impo umou -associa ed an igens in o DCs o induce hem o play he
ole o an igen p esen a ion and ac i a e T cells. Mos DC accines a e de i ed om monocy e-de i ed dend i ic cells [
19 ]. In immuno he apy s udies, umou cell lysa es we e loaded in o monocy e-de i ed dend i ic cells, and Mo
DC-based accina ion was shown o be well ole a ed and e ec i e. The ocus o DC-based accines was no only DC
cells hemsel es; he exosomes eleased by dend i ic cells we e paid a en ion. DC exosomes a e ine memb ane
esicles wi h bio s abili y, which can exp ess MHCI, MHC II, and co s imula o y molecules. Dend i ic cells ha e al eady
shown e icacy in he ea men o cance in clinical ials. Howe e , dend i ic cells ha e ye o demons a e clea
clinical bene i [20].
5. Cu en p og ess in cell based cance accines
In addi ion, pho o senso -induced dead and e op osis umou cells RAS-selec i e le hali y 3- induced immunogenici y
may also be s ongly immunogenic [21]. Modi ica ion o umou cells may also imp o e he e icacy o whole umo
cell accines.In mos cases, he pu pose o he modi ica ion is o imp o e an igen p esen a ion. This means ha
molecules ela ed o he immune esponse may be in ol ed he modi ica ion. Fo example, IL-21 and IL-7 a e wo
impo an ac o s ha can syne gis ically enhance T cell esponses.
The e is a accine wi h umo cells wi h gene ic modi ica ions The IL-21 and IL-7 ca ion showed mo e e iciency.
Double IL-15 ans ec o , NK modula o and memo yCT26 T cells and cu -o IL-15Rα ecei e The cells also guided
a eliable an i umo eac ion. Fu he mo e, se e al adju an modi ica ion app oaches ha e been used o modi y
accines, o example, dying umo cells modi ied wi h CpG-loaded nanopa icles we e ound o enhance an igen
p esen a ion ( 22).Finally, he combina ion o whole umo cell accines wi h immune checkpoin inhibi o (CPIs) is
becoming mo e common. I is designed o block pa hways ha supp ess ac i i y au o eac i e T cells. P og ammed
blocking o cell dea h-ligand 1 (PD-L1) and cy o oxic T lymphocy e p o ein 4 (CTLA-4) has al eady be
demons a ed imp o e cell pe o mance in he apeu ic accina ions [22]. Op imiza ion o immune cell- based
accines, especially DC accines, may in ol e mo e de ailed in o ma ion.
5.1. Vi us-based cance accines
One o he main ad an ages o i us -based accines is ha he accine can make an inna e and adap i e immune wo k
oge he o each e ec i e and long Immune esponse. The i us-based accine can be di ided in o h ee o ms:
inac i a ed, displayed li ing, o subuni s agains he i us ha can cause a umou . Oncoly ic i us accine and VEC
i us accine. The incidence o cance is epo ed o be abou 12%.
I is belie ed o be caused by i al in ec ions. Eps ein-Ba i us, hepa i is B i us, hepa i is C i us, and HPV a e he
mos common i uses associa ed wi h cance [23]. Inac i a ed whole i us accines ha e shown p omising e icacy
in he ea men o COVID-19 and Ebola [23]. Logically, hey would show simila e icacy in he ea men o i us-
associa ed cance s [23]. Howe e , he no ed ha hey a e p obably no used much in cance p obably because
o p oduc ion di icul ies and sa e y conce ns. Ins ead, wi h de elopmen s in bioenginee ing echnology, i us-
like pa icle app oaches a e inc easingly being used o he apy. Oncoly ic i uses a e a no el immuno he apy ha
kills umou cells and s imula es an i umo esponses. Upon in ec ion wi h oncoly ic i uses, umou cells p oduce ROS
and cy okines ha s imula e immune cells. Subsequen ly, oncolysis will occu and subs ances such as TAA will be
eleased [24]. Va ious clinical ials ha e al eady p o en he an i umo e icacy o oncoly ic i uses. Oncoly ic i uses
include he pes simplex i us, adeno i us, measles i us, accine i us, e o i us, and esicula s oma i is i us.
Among hem, T-VEC, a i s -gene a ion ecombinan p oduc o he pes simplex i us, was he mos s iking. Besides
he pes simplex i us, adeno i us is ano he widely used oncoly ic i us, which is also o en used as a deli e y ec o s o
ce ain genes [24]. Adeno i us is easy o handle, i s gene s uc u e is clea , and i is easy o each he gene T ans e and
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umou exp ession o he an igen. Second, Adeno i us has a e y b oad spec um o hos cell opism and i can be
quickly p epa ed in la ge quan i ies. In addi ion, mucosal in ec ion is an inhe en ea u e o adeno i uses. The e o e,
he adeno i us ec o is a p omising accine pla o m. Adeno i us-based p omise in p eclinical and clinical ials
[25]. Excep o adeno i uses, o he ec o s such as accines, len i i uses, and adeno i us- associa ed i uses a e also
used in umou accine pla o ms. Len i i uses and adeno i us- associa ed i uses ha e he unique abili y o achie e
s able and long- e m exp ession o ansgenes in non-di iding cells. As adeno i uses.
5.2. Pep ide-based cance accine
The cu en ocus o cance accines is con e ing whole, inac i a ed, o a enua ed pa hogens in o subuni accines.
Pep ide accines a e polypep ides made om known o p edic ed umou an igen epi opes. Due o he limi a ion o
MHC polymo phism and he small size o an igen epi opes hemsel es, he immunogenici y o pep ide-based accines
is weak. I is o en di icul o cause a obus immune esponse, which also leads o immune ole ance. Adju an s
a e combined wi h accines based on pep ides o s eng hen he immune esponse in gene al. No All a eas o p o ein
an igens a e also immunogenic Fo C cells and cells. Compa ed o inac i a ed umou cell accines, pep ide-
based accines induce a mo e a ge ed immune esponse agains key neu alizing epi opes. This ad an age in
immuni y is called immunodominance [26]. Pep ide-based cance accines usually equi e bo h CD8+ and CD4+ T cell
epi opes. CD8+ T cell epi opes ac i a e CTL an i umo immuni y h ough he an igen c oss-p esen a ion pa hway,
while CD4+ T cells ac i a e helpe T cells o main ain CTL unc ion. The leng h o he pep ide chain is mos ly
de e mined Pep ide sou ces pe o mance. The e is a sho pep ide Usually, he smalles epi ope CD8+ T cells and
sho Hal in i o. Pep ide TIS does no equi e special APC ea men and is di ec ly esponsible. MHC I APC
molecula o o he nuclea cells. Absu d Cos Ma al molecules equi ed o he op imal CD8 + T CTL p o oca ion is
es ic ed by cell ac i a ion. Thus, sho pep ides o en ac i a e CTLs ansien ly and also induce ole ance o CTLs
[26]. Mo eo e , by being sho , pep ides also end o be HLA ype es ic ed. Compa ed wi h sho pep ides, long
pep ides can p o ide b oade HLA co e age, including mul iple epi opes, while also suppo ing mo i ecogni ion
and binding o enhanced immunogenici y. Long pep ides need o be p ocessed by APCs a he han being di ec ly loaded
on o MHC molecules [26]. A e in e naliza ion, pa o he long pep ides decomposed by an endosomal way loaded
in o MHCII molecules, and hen CD4+ T Helpe is ecognized o he pa s a e in cy oplasmic o acuole cells Way and
c oss molecules MHC-I Ac i a e CD8+ T -cells [13]. Thus, long pep ide accines ha e g ea po en ial o induce du able
and e ec i e an i umo esponses. Sho pep ides a e usually p oduced by chemical syn hesis, while long pep ides
a e o en p oduced by p o ein exp ession sys ems. Immunogenici y a ies among ecombinan p o eins subuni
accines based on di e en exp ession pla o ms. Se e al exp ession pla o ms ha e been used o p oduce cance
accines, including Esche ichia coli (E. coli), plan s, yeas , insec cells, and mammalian cells. These p o eins
exp essed by mammal cells The closes o he na u al umou an igen. Baculo i us insec cell a e low -cos po en ial
sys ems and a e pa ially A e modi ica ion o a ge p o ein [12].
5.3. Nucleic acid based cance accines
The nucleic acid accine is coded he owne 's umou an igen and p o ides gene ic in o ma ion ha p oduces an igen
-based p o eins wi h no mal physiological ac i i y.
Exp essi e umou an igen can cause immunoscopic. Insu ance is applied om cance cells.Due o he ubiqui y
o enzymes, Di e ences in he s uc u e o RNA, DNA and mRNA. DNA is mo e s able han mRNA and pe sis s
in he body o a longe pe iod o ime. The e o e, ea ly nucleic acid accines we e mainly ocused on DNA accines.
DNA molecules mus en e he cell nucleus o s a T ansc ip ion, MRNA en e s he cy oplasm ansla e and exp ess he
an igen di ec ly. P e iously, MRNM The p oduc ion o an igens is ins an aneous and e icien . DNA accines equi e
an addi ional s ep o en e he cell nucleus, so hey gene a e a weake immune esponse han mRNA accines. Howe e ,
once he plasmid DNA en e s he nucleus, i can p oduce se e al copies o he mRNA, which p oduces mo e an igen han
a single molecule o mRNA. Addi ionally, DNA accines also ca y he po en ial isk o inse ional mu agenesis,
whe eas mRNA does no ha e he isk o inse ional and in eg a ion in o he genome.
5.4. DNA accines
Cance DNA accines a e based on bac e ial plasmids ha encode one o mo e cance an igens ha induce ac i a ion o
he inna e and adap i e immune esponses. Answe [27]. In 1990, Wol e al. Naked DNA was injec ed di ec ly in o
mouse muscle o obse e he exp ession o he co esponding p o ein.[14] The i s human ials o a DNA accine o
ea immunode iciency i us ype 1 (HIV) we e epo ed in 1998.[14] We ha e been s udying DNA o a long ime and
esul s a e s ill limi ed. Un il ecen ly, India App o ed COVVI-19 DNA accine.(ZycoV-D) was he i s DNA accine
app o ed o human use, ma king he eme gence o DNA accines o a ange o diseases. DNA accines induce
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humo al and cellula immune esponses. DNA - accines mus be en e ed A e being ans e ed An igen coded by
cy oplasm. These an igens a e ea ed and ep esen ed by CD8 + T and CD4 + cells Ac i a es speci ica ion by MHC I
and MHC II molecules Immune esponse. Mechanism o ac ion o DNA accines They can be di ided in o h ee
ca ego ies [12]: DNA hi Injec ed di ec ly in o body cells, such as muscle cells. Rea The an igen coded by ansla ion
and DNA is deli e ed di ec ly o CD8 +cell poisonous T lymphocy es by MHC-1 molecule. You The second me hod
is he an igen coded by he DNA Sha e cells a e eleased by sec e ion o apop osis. These pep ides a e phagocy osed,
p ocessed by APCs, and c oss-p esen ed by MHC II molecules o CD4+ T cells. The hi d pa hway is di ec ans ec ion
o DNA in o APCs. Endogenous an igens p oduced by APCs a e p ocessed and p esen ed o CD8+ and CD4+ T cells
by MHC I and MHC II, espec i ely (28). Ac i a ion CD4+ T lymphocy es induce humo al immuni y. CD8+ T cells
Di e en ia e in o CTLs and induce cellula immuni y. Di ec ans ec ion o DNA plasmids in o APCs In ade mal
adminis a ion is conside ed he mos impo an ou e o DNA accines agains cance [15]. In addi ion, CpG
mo i s in plasmid DNA help ac i a e he inna e immune esponse. CpG mo i s can in e ac wi h TLR9 as a dange signal.
TLR9 igge s a signalling cascade ha ac i a es NF-κB, IRAK and causes p oduc ion o in lamma o y chemokines
and cy okines [28]. Double-s anded s uc u es o DNA also ac i a e STING signalling channel. STING is he p ima y
DNA senso ha con ols a cascade o cy oplasmic DNA signals Thus, DNA accines a e no independen o TLRs. Induces
s ong adap i e immune esponses in STING-de icien mice (17). DNA accines can encode mul iple an igens o la ge
an igens. DNA accines ha e high speci ici y and sa e y, low p oduc ion cos s, and a e easy o anspo and s o e.
The inse ional mu a ion a e o DNA accines is lowe han he spon aneous mu a ions a e and he DNA a ely
binds o hos ch omosomes
.Fu he mo e, he umou an igen exp essed by DNA cance accines has he same species modi ica ion as he
na u al umou an igen. DNA cance Vaccines ha e speci ic ad an ages and op imized DNA Vaccines ha e p o en
ha e icacy in p eclinical models [15]. Howe e , DNA-Vaccines has only eached mino p og ess in he clinical ials o
hei bad immunogenici y [28].
5.5. mRNA accines
The FDA ecen ly app o ed wo mRNA accines agains COVID-19: Mode na's Spike ax and P ize 's BNT162b2.
BNT162b2 is also he i s mRNA accine app o ed o sale by he FDA. Due o he ad an ages o mRNA accines in
apidly esponding o he COVID-19 pandemic, he ma ke alue o mRNA accines has isen d ama ically. Cu en ly,
Cu eVac, BioNTech and Mode na a e he pionee s and leade s in he ield o in i o ansc ibed (IVT) mRNA
accines. mRNA accines a e a p omising cance accine pla o m in which exogenous syn he ic mRNA is
in oduced in o cells o p o ide a empla e o an igen syn hesis, and he exp essed an igens a e deli e ed o he
su ace o APCs ia MHC molecules o ac i a e an i umo immuni y. In 1990, scien is s we e success ul In i o,
Luci e , be a-galac osidase, Chlo amphenicol Ace yl T ans e ase exp essed MRNA. [29] wi h he accine. ji ikowski
disco e ed he MRNA Coding o oxy ocin and asop essin, which ha e been in oduced in diabe es, can obse e
empo a y changes. Diabe es insipidus wi hin a ew hou s a e injec ion 1992 [16]. Cu en ly, mRNA cance accines
ha e shown p omising clinical esul s in he ea men o a ious solid umou s [15]. Wha has u he been ound
is ha mRNA accines may imp o e he e icacy o o he accine ea men s. Fo example, mRNA accines encoding
chime ic ecep o s a ge ing CLDN6, exp essed in some solid cance cells, ha e been shown o enhance he e icacy
o claudin-CAR-T cells agains solid umou s [29]. mRNA accines a e mainly di ided in o non- eplica ing mRNA
and sel -ampli ying RNA (SAM). MRNA, which has no epe i i e posi ion, is composed o 7-me hylganosine (M7G)
5 '. CAP, 5'- on ansled a ea (5'-uUTR), open eading amewo k (OF), Cleaning Region 3 '(3'-UUTR) and 3'Poly (A)
Tail [13]. TSE elemen s a e impo an o MRNA's s abili y and se ies o ansc ip ion ac o s. E ec i e p o ein
ansla ion. 5' cap and 3' poly(A) ails can be enzyma ically added a e he i s IVT. In con as o mRNA is no eplaced
and SAM has wo OFRs. One encodes objec i e an igen, and ano he encodes i al eplica ion componen , enabling
long-las ing RNA ampli ica ion in cells. SAM is o igina ed om alpha i us, and i eplica es and magni ies in i o o
induce a pe sis en and e icien immune esponse. SAM allows he adminis a ion o small doses o accines while
p oducing la ge amoun s o an igen o e a pe iod o ime. Howe e , demand is high SAM in cance accines is
s ill in he p eclinical s age and i s clinical applica ion equi es u he esea ch [30]. mRNA cance accines
a ely eplica e [19, 10]. The e o e, we ocus p ima ily on non- eplica ing mRNAs.
6. Conclusion
The de elopmen o cance accines is an impo an b eak h ough in he ea men o solid umou s. In his e iew,
we summa ize he mechanisms o ac ion, op imiza ion s a egies, and clinical p og ess o cance accines, which a e
expec ed o acili a e he u u e de elopmen o cance accines. Vaccines. In addi ion, we highligh ed: Ba ie s o he
applica ion o cance accines The e o e, we o e combina ion he apies o umou esis ance. Imp o e clinical
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 21(01), 132-139
138
e icacy. Thanks o he ad ances in ou unde s anding o immunological mechanisms and sequencing echnologies,
pe sonalized cance accines can be de eloped apidly. Cus omized neoan igens Can induce ue umou -speci ic T
cell esponses. Cen al immune ole ance is limi ed. Howe e , by elimina ing umou cells exp essing speci ic
neoan igens, hey can inhibi umou cell p oli e a ion wi hou neoan igens [30]. Ta ge ing mul iple neoan igens in a
single accine May be a way o educe immune e asion and e ec i ely elimina e umou s. Highly e ec i e neoan igens
This needs o be u he p edic ed and iden i ied, bu cu en ly, some neoan igens may induce e ec i e an i umo
immune esponses. In addi ion, he subjec s o he apeu ic ials o cance accines a e mainly pa ien s wi h umou s
in whom adi ional ea men s ha e ailed and he disease has p og essed. Theo e ically, cance accine he apy is
mo e sui able o pa ien s wi h a comple e immune sys em, a lowe umou bu den, and a highe isk o elapse.
The e o e, u u e cance accine clinical ials should ake in o ull conside a ion he unc ion o he pa ien 's immune
sys em and umou bu den. In conclusion, cance accines a e p omising immuno he apeu ic agen s o s imula e he
immune sys em o kill umou s and es ablish immune su eillance. Howe e , much emains o be done o iden i y
neoan igens, de elop combina ion he apies, and op imize accine pla o ms be o e cance accines become an
e ec i e s a egy in immuno he apy.
Compliance wi h e hical s anda ds
Disclosu e o con lic o in e es
No con lic o in e es o be disclosed.
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