The anticancer efficiency of the xenogeneic vaccine and the indication for its use
Aim: To investigate the anticancer efficiency of the xenogeneic vaccine in different tumor models and to assess the possibility whether level of antibodies (Ab) specific for vaccine’s proteins can be used as an indication for its use. Methods: Mice with Lewis lung carcinoma (LLC), Ehrlich carcinoma...
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| Опубліковано в: : | Experimental Oncology |
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| Дата: | 2014 |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2014
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| Цитувати: | The anticancer efficiency of the xenogeneic vaccine and the indication for its use / T.V. Symchych, N.I. Fedosova, O.M. Karaman, L.M. Yevstratieva, H.S. Lisovenko, I.M. Voyeykova, H.P. Potebnia // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 79-84. — Бібліогр.: 33 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1859801688955682816 |
|---|---|
| author | Symchych, T.V. Fedosova, N.I. Karaman, O.M. Yevstratieva, L.M. Lisovenko, H.S. Voyeykova, I.M. Potebnia, H.P. |
| author_facet | Symchych, T.V. Fedosova, N.I. Karaman, O.M. Yevstratieva, L.M. Lisovenko, H.S. Voyeykova, I.M. Potebnia, H.P. |
| citation_txt | The anticancer efficiency of the xenogeneic vaccine and the indication for its use / T.V. Symchych, N.I. Fedosova, O.M. Karaman, L.M. Yevstratieva, H.S. Lisovenko, I.M. Voyeykova, H.P. Potebnia // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 79-84. — Бібліогр.: 33 назв. — англ. |
| collection | DSpace DC |
| container_title | Experimental Oncology |
| description | Aim: To investigate the anticancer efficiency of the xenogeneic vaccine in different tumor models and to assess the possibility whether level of antibodies (Ab) specific for vaccine’s proteins can be used as an indication for its use. Methods: Mice with Lewis lung carcinoma (LLC), Ehrlich carcinoma (EC) or Sarcoma 37 (S37) were immunized with a xenogeneic anticancer vaccine based on chicken embryo proteins (CEP) and its anticancer activity was examined. The level of specific Ab in the blood serum of non-immunized tumor-bearing mice was studied by ELISA. Results: CEP application statically significantly inhibited the growth of LLC (the index of tumor growth inhibition was 42.10–53.13% depending on the day of tumor growth); vaccinated mice with EC showed significant tumor growth inhibition and life prolongation by 34.48%. Among mice with S37, there was noticed no antitumor effect. The number of tumor-bearing non-immunized mice which have had pre-existing CEP-specific Ab did not differ depending on the tumor model. The level of CEP-specific Ab among mice with LLC and EC increased with the growth of the tumor volume, but it decreased among mice bearing S37. Probably, the low level of CEP-specific Ab alongside huge tumor burden shows it is futile to apply the CEP-based vaccine. Conclusion: Different tumor strains vary in their susceptibility to CEP-based vaccine. Probably, the low level of CEP-specific Ab when a tumor burden is huge shows it is futile to apply the CEP-based vaccine. Key Words: xenogeneic anticancer vaccine, chicken embryo proteins anticancer activity, Lewis lung carcinoma, Ehrlich carcinoma, Sarcoma 37, CEP-specific antibodies. Key Words: xenogeneic anticancer vaccine, chicken embryo proteins anticancer activity, Lewis lung carcinoma, Ehrlich carcinoma, Sarcoma 37, CEP-specific antibodies.
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| first_indexed | 2025-12-07T15:12:54Z |
| format | Article |
| fulltext |
Experimental Oncology 36, 79–84, 2014 (June) 79
THE ANTICANCER EFFICIENCY OF THE XENOGENEIC VACCINE
AND THE INDICATION FOR ITS USE
T.V. Symchych*, N.I. Fedosova, O.M. Karaman, L.M. Yevstratieva,
H.S. Lisovenko, I.M. Voyeykova, H.P. Potebnia
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine,
Kyiv 03022, Ukraine
Aim: To investigate the anticancer efficiency of the xenogeneic vaccine in different tumor models and to assess the possibility whe ther
level of antibodies (Ab) specific for vaccine’s proteins can be used as an indication for its use. Methods: Mice with Lewis lung carci-
noma (LLC), Ehrlich carcinoma (EC) or Sarcoma 37 (S37) were immunized with a xenogeneic anticancer vaccine based on chicken
embryo proteins (CEP) and its anticancer activity was examined. The level of specific Ab in the blood serum of non-immunized tumor-
bearing mice was studied by ELISA. Results: CEP application statically significantly inhibited the growth of LLC (the index of tumor
growth inhibition was 42.10–53.13% depending on the day of tumor growth); vaccinated mice with EC showed significant tumor growth
inhibition and life prolongation by 34.48%. Among mice with S37, there was noticed no antitumor effect. The number of tumor-
bearing non-immunized mice which have had pre-existing CEP-specific Ab did not differ depending on the tumor model. The level
of CEP-specific Ab among mice with LLC and EC increased with the growth of the tumor volume, but it decreased among mice be-
aring S37. Probably, the low level of CEP-specific Ab alongside huge tumor burden shows it is futile to apply the CEP-based vaccine.
Conclusion: Different tumor strains vary in their susceptibility to CEP-based vaccine. Probably, the low level of CEP-specific Ab when
a tumor burden is huge shows it is futile to apply the CEP-based vaccine.
Key Words: xenogeneic anticancer vaccine, chicken embryo proteins anticancer activity, Lewis lung carcinoma, Ehrlich carcinoma,
Sarcoma 37, CEP-specific antibodies.
The construction of xenogeneic anticancer
vaccines (AV) is a comparatively new but fairly pro-
mising field in cancer biotherapy. The development
of AV based on xenogeneic analogues of tumor associ-
ated antigens (TAA) was brought about by two facts:
1) tumor antigens are generally products of expres-
sion of unmutated patient genes which are tolerated
by the body’s immune system; 2) the use of homologi-
cal xenogeneic antigens can overcome immunological
tolerance to these proteins [1, 2].
Now a number of researches showed the abi-
lity of xenogeneic analogues to overcome immu-
nological tolerance to tumor antigens or proteins
connected to carcinogenesis [3–6]. The antitumor
efficiency of some xenogeneic vaccines was proved
by a number of experimental [2, 3, 5–8] and clinical
researches [9–11]. On the other hand, indications for
use of xenogeneic AV are not evident enough. In gene-
ral, it is not a problem in a case of those vaccines which
are based on the limited number of antigens: the tu-
mor’s expression of these antigens or proteins involved
in carcinogenesis is an indication for use of a relevant
vaccine. Nevertheless, the identification of tumor an-
tigenic spectrum by every patient requires much time
and expense. The problem is more acute for polyvalent
vaccines or vaccines based on tissue homogenates
and extracts. That is to say, it is urgent to find simple
and quick methods to predict the expedience of xeno-
geneic vaccine use. Xenogeneic vaccines certainly
cannot pretend to be “universal” vaccine, therefore
there is a still open question how to assess “the ap-
plicability spectrum” of every xenogeneic vaccine,
i.e. to choose the factors of their expedience for use.
Tumor and embryonic cells are believed to have
common features: embryonic cells express antigens
which are similar to oncofetal antigens of tumor
cells [12, 13]. Moreover, it is known from the literature
that the embryo cells of the chicken express proteins,
which share homology with the human and mouse tumor
antigens [3, 5, 14–16]. The literature tells us about suc-
cessful application of some proteins or genes of chicken
origin as a xenogeneic AV [3, 5, 8]. So, the development
of a xenogeneic vaccine based on chicken embryo pro-
teins (CEP) looks promising. In R.E. Kavetsky Institute
of Experimental Pathology, Oncology and Radiobiology
(IEPOR) of NAS of Ukraine, the work is proceeding with
elaboration of the xenogeneic AV based on CEP.
The aim of this particular research project has
been to study the anticancer efficiency of the xeno-
geneic vaccine based on CEP on different models
of cancerous growth and assess the possibility to apply
the level of CEP-specific antibodies (Ab) as an indica-
tion for use of the vaccine.
MATERIALS AND METHODS
The study has been carried out on male C57Bl/6 and
Balb/c mice 2–2.5 months old weighting 19–20 g,
bred in the vivarium of R.E. Kavetsky IEPOR of NAS
of Ukraine. The use and care of experimental animals
have been performed in accordance with standard
international rules on biologic ethics and was ap-
Submitted: May 21, 2014.
*Correspondence: E-mail: symchychtv@gmail.com
Abbreviations used: Ab — antibodies; AV — anticancer vaccine;
CEP — chicken embryo proteins; EC — Ehrlich carcinoma; ILSP — in-
dex of life span prolongation; ITGI — index of tumor growth inhibi-
tion; LLC — Lewis lung carcinoma; MII — metastasis inhibition index;
S37 — sarcoma 37; TAA — tumor associated antigens.
Exp Oncol 2014
36, 2, 79–84
80 Experimental Oncology 36, 79–84, 2014 (June)
proved by Institutional Animal Care and Use Commit-
tee [17, 18].
Anticancer efficacy of CEP was examined when
vaccination was applied after tumor transplanta-
tion — so called therapeutic vaccination. Three dif-
ferent tumor strains were used: Lewis lung carcinoma
(LLC), Ehrlich carcinoma (EC) and Sarcoma 37 (S37).
To establish tumors, cancer cells suspension was in-
jected i.m. in the right hind leg at a dose of 4•105 cells/
mouse (LLC, EC) or 5•105 cells/mouse (S37). Unvacci-
nated mice with the tumor of relevant strain are referred
as a control.
LLC bearing mice were immunized on days 1st, 8th
and 15th after tumor injection.
EC bearing mice were immunized on days 2nd, 5th,
and 8th after tumor injection.
Vaccination of S37 bearing mice has been per-
formed by three schemata: at 1st, 8th, 15th days
(scheme 1, group 1), at 2nd, 5th, and 8th days (sheme 2,
group 2) and at 7th, 14th, 28th days after tumor cell
transplantation (scheme 3, group 3).
In all the cases, immunizations were performed
s.c. with 0.3 ml of CEP solution per mouse (protein
concentration 0.3 mg/ml).
Mouse sera were collected on days 7th, 14th, 21st
and 28th after tumor transplantation. Sera were frozen
and stored at −20 °С. By an enzyme-linked immu-
nosorbent assay (ELISA) sera were tested for CEP-
specific or TAA specific Ab as described in [19]. Briefly,
the CEP or TAA at 0.3 mg/mL were incubated for
24 h at 4 °C on 96-cells microtiter plates. Nonspecific
binding was blocked with 3% BSA for 1 h at 37 °C. Sera
were added at dilution 1:20 (sera dilution was se-
lected in preliminary tests). Bound Ab were revealed
using goat antimouse IgG and IgM peroxidase conju-
gate (Dako) and o-phenyldiamine/H2O2 substrates.
Plates were read at 492 nm in an MicroELISA (Stat
Fax 2100, USA) auto-reader. The negative control
consisted of naїve mouse sera in the same dilution.
The results are presented as factor F [20]:
F = ODexperiment/ODcontrol, (1)
where ODexperiment stand for optical density of cells
with serum of tumor-bearing mice, ODcontrol stand
for optical density of cells with naïve mice serum.
The F value exceed 2 was taken as indication of Ab-
positive serum.
CEP was prepared as follows [21]. Briefly, 7 days
chicken embryos were rinsed two times in cold NaCl
0.9% solution, homogenized and then extracted
with NaCl 0.9% solution, containing 0.1% EDTA,
for 60 min at 4 °C by agitation. Following extraction,
chicken embrio tissue was removed by centrifuga-
tion at 1.500 g for 30 min. The resulting supernatant
was collected and frozen at −20 °C. TAA of LLC,
EC and S37 were prepared by three consecutive cycles
of freezing and melting of cells suspension. Following
the last melting, cell debris was removed by centrifuga-
tion at 1.500 g for 30 min. The resulting supernatants
were collected and frozen at −20 °C. Concentration
of proteins in the extracts was measured by Greenberg
and Craddock assay [22]. The same extracts were
used in all the experiments, described in the article.
Tumor dimensions were measured with calipers,
and tumor volumes were calculated according
to the formula:
tumor volume = 4/3π • width2 • length • 0,5 (2)
Index of tumor growth inhibition (ITGI) was calcu-
lated according to the formula:
Vcontrol mice — Vimmunized miceITGI = —————————————————— 100%, (3)
Vcontrol mice
where Vcontrol mice and Vimmunized mice stand for mean
tumor volume in control unimmunized and immunized
mice respectively [23].
Index of life span prolongation (ILSP) was calcu-
lated as following:
survival timeimmunized mice — survival timecontrol miceILSP = ————————————————————————————————————— 100%, (4)
survival timecontrol mice
where survival timeimmunized mice and survival timecontrol mice
stand for survival time (days) in immunized and control
groups respectively [23].
Metastasis inhibition index (MII) was calculated
as following:
Аc • Вc — Аi • ВiMІІ = ————————————— 100%, (5)
Аc • Вc
Аc and Аi stand for number of mice bearing lung
metastases in groups of control and immunized mice
respectively. Вc and Вi stand for mean number of lung
metastases in groups of control and immunized mice
respectively [24].
Pearson correlation coefficient (r) was adjusted for
sample size [25].
RESULTS
Study into anticancer activity of the CEP-based
vaccine on the model of LLC. According to obtained
results, tumors formed on 9–11th day after the LLC cells
injection in six out of ten (60%) animals of the control
and treatment groups. The tumor volume (Fig. 1) in im-
munized animals for the whole period of observation
was smaller compared to the results of control mice
(р < 0.05 before day 20 and р < 0.1 since 25th until 28th
day of tumor growth).
0
1000
2000
3000
4000
5000
14 18 20 25 28
Days of tumor growth
Tu
m
or
v
ol
um
e,
m
m
3
Control
CEP
Fig. 1. The tumor volume of vaccinated with CEP-based vaccine
and control mice bearing LLC
On the 28th day after the LLC implantation, the ani-
mals were euthanized and metastases were assessed
Experimental Oncology 36, 79–84, 2014 (June) 81
(Table 1). According to the obtained data, the mean
volume of metastases in the group CEP was 2.2 times
smaller comparing to the control group. The mean num-
ber of metastases per mouse in the group tended to de-
crease among the immunized mice (0.05 < р < 0.1 com-
paring to the control group). MII for the immunized
animals was 77.56% and 66.35% — per group in general
and per animals bearing metastases respectively.
Table 1. Metastases in vaccinated and unvaccinated mice bearing LLC
Group Metastases rate, %
(sample size/mts+)
Metastases
volume, mm3
Metastases number
per mouse
bearing
metastases
per mouse
in a group
Control 85.71 ± 12.37 (5/5) 10.11 ± 5.39 10.4 ± 3.4 10.4 ± 3.4
CEP 66.67 ± 19.25 (6/4) 4.61 ± 3.98 4.5 ± 1.97 3.0 ± 1.57*
Notes: * р < 0.1 comparing to the control group.
Hence, the AV based on CEP had a significant an-
titumor and some antimetastatic effect.
Study into anticancer activity of the CEP-based
vaccine on the model of EC. An anticancer effect
of the CEP-based vaccine was evident in the model
of EC. Although tumors formed in every unvaccinated
and vaccinated animal on the 5–7th day after the trans-
plantation (Table 2), the immunized mice showed
significant inhibition of tumor growth (Fig. 2).
Table 2. The latent period of tumor formation and the survival time for
vaccinated with the CEP-based vaccine and control mice bearing EC
Group
(sample size)
Latent period of tu-
mor formation (days)
Survival time
(days)
Median survival
(days)
Control (14) 5.50 ± 0.34 43.77 ± 2.35 44.0
CEP (14) 6.36 ± 0.78 58.86 ± 4.09* 55.0
Notes: *p < 0.05 comparing to control group.
0
1000
2000
3000
4000
5000
6 9 13 16 20 23 27 30 34 37
Days of tumor growth
Tu
m
or
v
ol
um
e,
m
m
3
Control
CEP
Fig. 2. The tumor volume of vaccinated with CEP-based vaccine
and control mice bearing EC
Significant difference (p < 0.05) in tumor volu me
between unvaccinated and vaccinated animals was evi-
dent since the 13th day, i.e. after the end of vaccination.
In particular, on the 13th and 16th day of tumor growth ITGI
in the group of vaccinated mice was 50.57 and 50.74%
respectively. Later the diffe rence is gradually getting
smaller (46.11 and 43.27% on the 20th and 23rd day of tu-
mor growth respectively), but it stays higher than by 20%
until the 30th day, when animals in the control group start
dying. As a result of tumor growth inhibition, survival time
in the group of vaccinated mice increased (р < 0.05): the
ILSP in the CEP group reached 34.48%.
To sum up, using CEP on the model EC inhibited
tumor growth, and, as a result, significantly lengthened
the life span of tumor-bearing animals.
Study into anticancer activity the CEP-based
vaccine on the model of S37. The anticancer ef-
fect of CEP in case of S37-bearing mice was inves-
tigated applying different schemata of vaccination;
however, there was no significant difference between
groups of vaccinated and unvaccinated animals. So,
Table 3 illustrates the data about the latent period
of tumor forming and the survival time of immunized
animals under different schemata: none of indices
between the groups differ significantly.
Table 3. The latent period of tumor formation and the survival time for vac-
cinated with the CEP-based vaccine and control mice bearing S37
Group
(sample size)
Latent period of tu-
mor formation (days)
Survival time
(days)
Median survival
(days)
Control (15) 6.93 ± 0.29 45.67 ± 3.79 43.0
CEP № 1 (6) 6.67 ± 0.37 42.50 ± 3.81 41.0
CEP № 2 (7) 7.14 ± 0.44 34.57 ± 2.05 33.0
CEP № 3 (15) 7.00 ± 0.20 41.93 ± 2.12 42.0
The tumor volume of unimmunized and immunized
mice bearing S37 did not differ significantly, though
different schemata of vaccination were applied (Fig. 3).
In other words, immunization did not affect signifi-
cantly any indices of tumor growth; so we considered
S37 were resistant to the CEP-based vaccine.
Control
CEP № 1
CEP № 2
CEP № 3
0
500
1000
1500
2000
2500
3000
3500
9 13 16 20 23 27 30 34
Days of tumor growth
Tu
m
or
v
ol
um
e,
m
m
3
Fig. 3. The tumor volume of vaccinated with CEP-based vaccine
and control mice bearing S37
As it appeared, different tumor strains differ
in susceptibility to the CEP-based vaccine. The ques-
tion arises whether there are any criteria according
to which it would be possible to predict the efficiency
of the CEP-based vaccine.
The evaluation of CEP-specific Ab in blood
serum of tumor-bearing mice as an indication for
use of the anticancer xenogeneic vaccine based
on CEP. The blood serum from unvaccinated mice
bearing tumors (LLC, EC and S37) on different days
after tumor cells injections (on the 7th, 14th, 21st and
28th day) was taken and checked for its ability to react
with its own tumor antigens (TAA) and CEP and the cor-
relation coefficient between the level of CEP-specific
or TAA-specific Ab and tumor volume was calculated.
Table 4 compares the portion of animals bearing
different tumors whose blood serum was positive for
TAA- and CEP-specific Ab. It is obvious that the num-
ber of animals in whose blood serum CEP- and TAA-
specific Ab were detected was approximately equal.
However, the portion of S37-bearing mice whose blood
serum was positive for CEP-specific Ab was slightly
82 Experimental Oncology 36, 79–84, 2014 (June)
lower than that (0.05 < р < 0.1) whose serum was
positive for their own TAA.
Table 4. The portion of blood serum samples positive for TAA- and CEP-
specific Ab depending on tumor strains
Tumor
strain
Portion of blood serum samples positive for
TAA-specific Ab, % (n) CEP-specific Ab, % (n)
S37 91.67 ± 5.64 (22 out of 24) 70.83 ± 9.28 (17 out of 24)*
EC 81.82 ± 8.42 (18 out of 22) 77.27 ± 9.17 (17 out of 22)
LLC 83.33 ± 7.61 (20 out of 24) 79.17 ± 8.29 (19 out of 24)
Notes: *0.05 < р < 0.1 comparing to a portion of blood serum samples which
are positive for TAA-specific Ab
The level of TAA-specific Ab in blood serum of tu-
mor-bearing mice was almost the same and did not
depend on the tumor strain or the day after tumor
transplantation (Fig. 4, a). As a result, there was not
found any correlation between the level of TAA-specific
Ab and tumor volume (see Table 5, where correlation
coefficients are presented).
0
2
4
6
8
10
12
14
7 14 21 28
Days of tumor growth
Fa
ct
or
S37
LLC
EC
0
2
4
6
8
10
12
14
7 14 21 28
Days of tumor growth
Fa
ct
or
a
b
Fig. 4. The level of TAA- (a) or CEP-specific (b) Ab in blood serum
of mice bearing different tumors, depending on the term after
the tumor cells injection
Table 5. Pearson correlation coefficient (r) between the tumor volume
and the level of TAA- or CEP-specific Ab depending on the tumor strain
Tumor strain
Correlation coefficient between tumor volume
and level of
TAA-specific Ab CEP-specific Ab
S37 0.04 −0.48**
EC −0.09 0.67*
LLC 0.26 0.42**
Notes: *р < 0.05; **р < 0.07.
The level of CEP-specific Ab varied and differed more
significantly (Fig. 4, b). For example, mice with S37 showed
the highest level of CEP-specific Ab on the 7th day after
tumor transplantation, which was decreasing gradually
and significantly (p < 0.05 comparing to the 7th day) until
the 28th day of the experiment. In contrast, EC-bearing
mice had the lowest level of CEP-specific Ab on the 7th day,
but it statistically significantly grew until the 28th day of tu-
mor growth. In the group of LLC-bearing mice, the level
of CEP-specific Ab gradually increased, but there was
no statistically significant difference between indices
on different days of tumor growth.
So, there was a strong, but multidirectional correla-
tion between the level of CEP-specific Ab and tumor
volume (see Table 5): the correlation was positive
for mice bearing LLC and EC (r = 0.42; р < 0.07 and
r = 0.67; р < 0.05 respectively), but it was negative for
mice bearing S37 (r = −0.48; р < 0.07).
So, the detection of CEP-specific Ab in blood
serum per se cannot be applied as an indication for
use of the CEP-based vaccine, as long as the same
portion of mice bearing resistant and nonresistant
tumor strains were positive for it. However, if the
level of CEP-specific Ab is low, but a tumor burden
is huge or the level of Ab is decreasing while a tumor
is growing, it possibly can indicate the tumor is resis-
tant to the CEP-based vaccine.
DISCUSSION
According to the results, the antitumor efficiency
of CEP was evident in the case of two out of three tumor
strains used in the study. The high anticancer efficiency
of CEP was shown on two models of carcinoma: EC (the
tumor came into being as spontaneous breast cancer
[26]) and LLC (the tumor came into being as lung cancer
[26]); however, sarcoma (S37 started to exist as a breast
tumor, but through many transplantations it turned into un-
differentiated polymorphous cell sarcoma [26]) turned out
to be resistant to the CEP-based vaccine both at different
therapeutic schemata of vaccination and at prophylac-
tic — before tumor was transplanted — one (the data are
not shown). Since the tumor models, used in the study,
differ in histogenesis, we can assume that the anticancer
efficiency of the CEP-based vaccine depends on this
factor. However, it is impossible to prove or disprove this
assumption in the scope of this work, because the number
of model tumors (only 3) is not enough for this.
The fact should be pointed up that both “sensitive”
to the vaccine tumors (LLC and EC) are undifferenti-
ated or poorly differentiated carcinomata. The low
level of tumor differentiation generally is associated
with a worse prognosis [27]. It can be assumed that
the application of the vaccine based on CEP, probably,
can improve the results of treatment in case of un- and
poorly differentiated carcinomata.
On the other hand, the obtained results — diffe-
rent anticancer efficiency in the case of different tumor
models — once more point to the necessity to find a reli-
able indication for use of the CEP-based vaccine. Most
prognostic and diagnostic markers that are used now
in clinical and laboratorial practice are based on detecting
in serum specific proteins, so-called oncomarkers
or Ab specific to them. Now a growing body of literature
points to the importance to detect in serum oncomar-
kers specific Ab as a more sensitive method [28–30].
The advantage of the latter is due to several factors.
Particularly, the levels of oncomarkers sufficient for de-
tection in serum appear at relatively later stages of tumor
Experimental Oncology 36, 79–84, 2014 (June) 83
growth when it already has clinical signs. Meanwhile,
Ab specific to these oncomarkers can be detected
at earlier stages of tumor growth, sometimes even before
clinical signs of a tumor [31, 32]. Therefore, we decided
to check whether the presence of CEP-specific Ab can
serve as an indication for use of the vaccine.
It was shown that some portion of mice bearing
resistant or nonresistant tumor strains was positive for
CEP-specific Ab: 70.73 ± 9.28% of S37 bearing mice
(considered as resistant tumor) and 77.27 ± 9.17% and
79.17 ± 8.29% of EC and LLC bearing mice respectively
expressed CEP-specific Ab in their blood serum. So,
CEP-specific Ab in the blood serum per se cannot
be applied as an indication for use of the CEP-based
xenogeneic vaccine. Changes in CEP-specific Ab le-
vels were more informative. In the case of S37 bearing
mice the level of CEP-specific Ab was decreasing while
tumor was growing (correlation coefficient was −0.48).
Pro bably, CEP-specific Ab have formed circulating
immune complexes, so they could not be detected
in ELISA, or the level of CEP-specific Ab decreased
during the formation of immune response to the tumor
as having lower affinity to TAA of S37. On the contrary,
in the case of “sensitive” LLC or EC the level of CEP-
specific Ab was constantly increasing. Considering
that, in the process of immune response formation
the number of Ab with higher affinity is growing (other-
wise known as affinity maturation [33]), we may assume
that CEP more resemble EC’s or LCC’s TAA (or contain
more proteins which share homology with these tumor
antigens), than that of S37. That is why immuniza-
tion with CEP has no effect on S37. So, the low level
of CEP-specific Ab together with a huge tumor burden
may indicate that tumor is resistant to the CEP-based
AV therapy.
In conclusion, the application of the CEP-based
vaccine to animals with LLC and EC had anticancer and
antimetastatic effects: statistically significant tumor
growth inhibition (both models), statistically signifi-
cant lengthening of survival time by 34.48% (EC) and
the inhibition of metastasizing of LLC — Index of me-
tastases inhibition reached 77.56%. The CEP-based
vaccine did not have any anticancer effect in the case
of S37. Detection of CEP-specific Ab in a blood serum
per se cannot be applied as an indication for use
of the CEP-based vaccine. However, the low level
of CEP specific Ab when tumor burden is huge points
to the unfeasibility of vaccine based on CEP.
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Copyright © Experimental Oncology, 2014
|
| id | nasplib_isofts_kiev_ua-123456789-145335 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1812-9269 |
| language | English |
| last_indexed | 2025-12-07T15:12:54Z |
| publishDate | 2014 |
| publisher | Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| record_format | dspace |
| spelling | Symchych, T.V. Fedosova, N.I. Karaman, O.M. Yevstratieva, L.M. Lisovenko, H.S. Voyeykova, I.M. Potebnia, H.P. 2019-01-20T16:33:56Z 2019-01-20T16:33:56Z 2014 The anticancer efficiency of the xenogeneic vaccine and the indication for its use / T.V. Symchych, N.I. Fedosova, O.M. Karaman, L.M. Yevstratieva, H.S. Lisovenko, I.M. Voyeykova, H.P. Potebnia // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 79-84. — Бібліогр.: 33 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/145335 Aim: To investigate the anticancer efficiency of the xenogeneic vaccine in different tumor models and to assess the possibility whether level of antibodies (Ab) specific for vaccine’s proteins can be used as an indication for its use. Methods: Mice with Lewis lung carcinoma (LLC), Ehrlich carcinoma (EC) or Sarcoma 37 (S37) were immunized with a xenogeneic anticancer vaccine based on chicken embryo proteins (CEP) and its anticancer activity was examined. The level of specific Ab in the blood serum of non-immunized tumor-bearing mice was studied by ELISA. Results: CEP application statically significantly inhibited the growth of LLC (the index of tumor growth inhibition was 42.10–53.13% depending on the day of tumor growth); vaccinated mice with EC showed significant tumor growth inhibition and life prolongation by 34.48%. Among mice with S37, there was noticed no antitumor effect. The number of tumor-bearing non-immunized mice which have had pre-existing CEP-specific Ab did not differ depending on the tumor model. The level of CEP-specific Ab among mice with LLC and EC increased with the growth of the tumor volume, but it decreased among mice bearing S37. Probably, the low level of CEP-specific Ab alongside huge tumor burden shows it is futile to apply the CEP-based vaccine. Conclusion: Different tumor strains vary in their susceptibility to CEP-based vaccine. Probably, the low level of CEP-specific Ab when a tumor burden is huge shows it is futile to apply the CEP-based vaccine. Key Words: xenogeneic anticancer vaccine, chicken embryo proteins anticancer activity, Lewis lung carcinoma, Ehrlich carcinoma, Sarcoma 37, CEP-specific antibodies. Key Words: xenogeneic anticancer vaccine, chicken embryo proteins anticancer activity, Lewis lung carcinoma, Ehrlich carcinoma, Sarcoma 37, CEP-specific antibodies. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions The anticancer efficiency of the xenogeneic vaccine and the indication for its use Article published earlier |
| spellingShingle | The anticancer efficiency of the xenogeneic vaccine and the indication for its use Symchych, T.V. Fedosova, N.I. Karaman, O.M. Yevstratieva, L.M. Lisovenko, H.S. Voyeykova, I.M. Potebnia, H.P. Original contributions |
| title | The anticancer efficiency of the xenogeneic vaccine and the indication for its use |
| title_full | The anticancer efficiency of the xenogeneic vaccine and the indication for its use |
| title_fullStr | The anticancer efficiency of the xenogeneic vaccine and the indication for its use |
| title_full_unstemmed | The anticancer efficiency of the xenogeneic vaccine and the indication for its use |
| title_short | The anticancer efficiency of the xenogeneic vaccine and the indication for its use |
| title_sort | anticancer efficiency of the xenogeneic vaccine and the indication for its use |
| topic | Original contributions |
| topic_facet | Original contributions |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/145335 |
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