Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin
Aim: To study in vivo efficacy of combined administration of cancer vaccine (CV), interferon (IFN) and inducer of endogenous IFN — amixin. Materials and Methods: Sarcoma-37 cells were transplanted to female Balb/c mice. For the treatment, CV prepared from sarcoma-37 cells with the use of cytotoxic l...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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| Zitieren: | Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin / G.P. Potebnya, G.S. Lisovenko, N.V. Trokhimenko, N.L. Cheremshenko, G.V. Didenko, A.S. Reder, S.A. Andronati // Experimental Oncology. — 2008. — Т. 30, № 4. — С. 319–323. — Бібліогр.: 24 назв. — англ. |
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irk-123456789-1399332018-06-22T03:04:43Z Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin Potebnya, G.P. Lisovenko, G.S. Trokhimenko, N.V. Cheremshenko, N.L. Didenko, G.L. Reder, A.S. Andronati, S.S. Original contributions Aim: To study in vivo efficacy of combined administration of cancer vaccine (CV), interferon (IFN) and inducer of endogenous IFN — amixin. Materials and Methods: Sarcoma-37 cells were transplanted to female Balb/c mice. For the treatment, CV prepared from sarcoma-37 cells with the use of cytotoxic lectines from B. subtilis B-7025, murine IFN and amixin or their combinations were used. IFN production, content of circulating immune complexes and level of specific IgG antibodies in blood serum were determined by standard immunologic methods. Results: Using solid form of sarcoma-37 it has been shown that introduction of IFN and amixin significantly elevated efficacy of vaccine therapy, in particular index of tumor growth inhibition reach 89.2% and 81.7%. Upon combined use of CV and IFN or CV and amixin (25 mg/kg) respectively. Significant prolongation of average life span of the animals treated with CV and IFN or CV and amixin (25 mg/kg) has been registered (up to 92.7 ± 10.4 and 95.0 ± 6.2 days respectively, vs 46.8 ± 1.5 days for control animals). Conclusion: Obtained results have shown expediency of the development of schemes for combined introduction of CV with exogenous IFN, and with inducer of endogenous IFN (amixin) for elevation of efficacy of vaccine therapy. Цель: изучить в эксперименте эффективность комбинированной схемы введения противоопухолевой вакцины (CV) с интерфероном (ИФН) и индуктором эндогенного ИФН — амиксином. Материалы и методы: саркому-37 трансплантировали мышам-самкам Balb/c. Для лечения использовали CV, приготовленную из клеток саркомы-37 с помощью цитотоксических лектинов B. subtilis B-7025, мышиный ИФН (1000 ед.) и амиксин (10 и 25 мг/кг). Иммунологические исследования включали определение в сыворотке крови титров ИФН, количества циркулирующих иммунных комплексов и уровня специфических противоопухолевых IgG-антител. Результаты: на модели солидной формы саркомы-37 показано, что применение ИФН и амиксина достоверно способствует повышению результатов вакцинотерапии, а именно, при комбинированном использовании CV и ИФН индекс торможения опухолевого роста (ИТО) достигал 89,2%; при сочетании CV и амиксина (25 мг/кг) ИТО составил 81,7%. Зарегистрировано существенное увеличение средней продолжительности жизни животных, получивших CV с ИФН или амиксином (25 мг/кг), до 92,7 ± 10,4 и 95,0 ± 6,2 сут соответственно, по сравнению с такой контрольных мышей (46,8 ± 1,5 сут, p < 0,05). Выводы: полученные результаты свидетельствуют о перспективности разработки комбинированных схем введения CV как с препаратом экзогенного ИФН, так и с индуктором эндогенного ИФН (амиксин), что позволяет повысить эффективность вакцинотерапии. 2008 Article Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin / G.P. Potebnya, G.S. Lisovenko, N.V. Trokhimenko, N.L. Cheremshenko, G.V. Didenko, A.S. Reder, S.A. Andronati // Experimental Oncology. — 2008. — Т. 30, № 4. — С. 319–323. — Бібліогр.: 24 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/139933 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions Potebnya, G.P. Lisovenko, G.S. Trokhimenko, N.V. Cheremshenko, N.L. Didenko, G.L. Reder, A.S. Andronati, S.S. Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin Experimental Oncology |
| description |
Aim: To study in vivo efficacy of combined administration of cancer vaccine (CV), interferon (IFN) and inducer of endogenous IFN — amixin. Materials and Methods: Sarcoma-37 cells were transplanted to female Balb/c mice. For the treatment, CV prepared from sarcoma-37 cells with the use of cytotoxic lectines from B. subtilis B-7025, murine IFN and amixin or their combinations were used. IFN production, content of circulating immune complexes and level of specific IgG antibodies in blood serum were determined by standard immunologic methods. Results: Using solid form of sarcoma-37 it has been shown that introduction of IFN and amixin significantly elevated efficacy of vaccine therapy, in particular index of tumor growth inhibition reach 89.2% and 81.7%. Upon combined use of CV and IFN or CV and amixin (25 mg/kg) respectively. Significant prolongation of average life span of the animals treated with CV and IFN or CV and amixin (25 mg/kg) has been registered (up to 92.7 ± 10.4 and 95.0 ± 6.2 days respectively, vs 46.8 ± 1.5 days for control animals). Conclusion: Obtained results have shown expediency of the development of schemes for combined introduction of CV with exogenous IFN, and with inducer of endogenous IFN (amixin) for elevation of efficacy of vaccine therapy. |
| format |
Article |
| author |
Potebnya, G.P. Lisovenko, G.S. Trokhimenko, N.V. Cheremshenko, N.L. Didenko, G.L. Reder, A.S. Andronati, S.S. |
| author_facet |
Potebnya, G.P. Lisovenko, G.S. Trokhimenko, N.V. Cheremshenko, N.L. Didenko, G.L. Reder, A.S. Andronati, S.S. |
| author_sort |
Potebnya, G.P. |
| title |
Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin |
| title_short |
Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin |
| title_full |
Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin |
| title_fullStr |
Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin |
| title_full_unstemmed |
Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin |
| title_sort |
elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2008 |
| topic_facet |
Original contributions |
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http://dspace.nbuv.gov.ua/handle/123456789/139933 |
| citation_txt |
Elevation of efficacy of cancer vaccine combined with interferon and inducer of endogeneous interferon synthesis amixin / G.P. Potebnya, G.S. Lisovenko, N.V. Trokhimenko, N.L. Cheremshenko, G.V. Didenko, A.S. Reder, S.A. Andronati // Experimental Oncology. — 2008. — Т. 30, № 4. — С. 319–323. — Бібліогр.: 24 назв. — англ. |
| series |
Experimental Oncology |
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2025-07-10T09:24:18Z |
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2025-07-10T09:24:18Z |
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| fulltext |
Experimental Oncology 30, 319–323, 2008 (December) 319
Unsatisfactory results of traditional methods of cancer
therapy determine the need for search of new means ele
vating anticancer resistance of organism. Activation of the
mechanisms of immune surveillance is an important way
to solve the task. Presently the development of immuno
therapeutical approaches, in particular, cancer vaccines
(CV) is considered as the most promising approach.
Analysis of modern data evidence on high prophylactic
and therapeutic efficacy of combined use of specific CV
with adjuvants of different origin [1, 2], including various
cytokines able to stimulate immune response [3, 4].
Interferon (IFN) was among the first cytokines success
fully applied in clinical practice for activation of unspecific
resistance upon viral infections and immunodeficiency
state [5]. IFN as natural factor of antitumor defense is one
of key modulators of immune response, and influences
the processes of antigen recognition, differentiation,
recruitment and functional activity of immunocompetent
cells. Also IFN has direct influence on tumor growth and
differentiation and act as apoptosis inducer [6, 7].
Effects of IFN related to elevation of tumor immu
nogenecity and its altered sensitivity to cytotoxic and
differentiationstimulating action of Tlymphocytes are
of particular interest [7], as well as the role of IFN at
combination with other biological agents. The special
attention is focused on the study of effects of IFN com
bined with active specific immunization [8–10].
That’s why the search for compounds able to activate
synthesis of endogeneous IFN — so called IFN inducers,
is of great importance [11, 12]. Amixin (tyrolon, 2,7bis
[2(diethyamino) etoxy] fluorenon9 dihydrochloride) is
a peroral low molecular weight inducer of endogenous
IFN that may be used for prophylaxis and therapy of
a number of diseases. Activity of this preparation is related
to its immunomodulating properties, ability to normalize
impaired immune reaction of organism, renew a balance of
important elements of immune system [13–15]. The data
on significant antitumor activity of amixin were obtained in
experimental studies using model tumors, and in clinical
trials for melanoma, breast cancer, renalcell cancer [13].
Moreover, it has been shown that combined use of amixin
and anticancer drugs promoted growth inhibition of ex
perimental tumors and decreased metastasis rate [16].
In our earlier studies it has been shown that intro
duction of IFN to CV significantly elevated efficacy of
vaccine therapy of Lewis lung carcinoma [17]. The aim
of present research was to evaluate possible benefits
of the use of amixin for elevation of CV efficacy, and to
compare the obtained results with these for IFN.
MATERIALS AND METHODS
In the work, female Balb/c mice weighting 18–20 g,
2.0–2.5 months old bred in the vivarium of IEPOR
NASU (Kyiv, Ukraine) were used. As tumor model, solid
form of sarcoma37 was used.
Experimental animals (n = 8 per group) were routinely
transplanted intramuscularly with 5.0 х 105 tumor cells,
and received the treatment according to the scheme
of experiment (Table 1). CV was prepared from sar
coma37 cells and cytotoxic lectine (CL) from B. subtilis
B-7025 according to the method [18, 19]. CV was admini
stered 5 times at equal doses (0.3 ml) subcutaneously
on days 1, 4, 8, 12 and 15 after tumor transplantation.
ELEVATION OF EFFICACY OF CANCER VACCINE COMbINED
wITH INTERFERON AND INDUCER OF ENDOGENEOUS
INTERFERON SYNTHESIS AMIXIN
G.P. Potebnya1, *, G.S. Lisovenko1, N.V. Trokhimenko1, N.L. Cheremshenko1,
G.V. Didenko1, A.S. Reder2, S.A. Andronati2
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology NAS of Ukraine, Kyiv 03022,
Ukraine
2O.V. Bogatsky Physico-Chemical Institute NAS of Ukraine, Odesa 65011, Ukraine
Aim: To study in vivo efficacy of combined administration of cancer vaccine (CV), interferon (IFN) and inducer of endogenous IFN — amixin.
Materials and Methods: Sarcoma-37 cells were transplanted to female Balb/c mice. For the treatment, CV prepared from sarcoma-37 cells
with the use of cytotoxic lectines from B. subtilis B-7025, murine IFN and amixin or their combinations were used. IFN production,
content of circulating immune complexes and level of specific IgG antibodies in blood serum were determined by standard immunologic
methods. Results: Using solid form of sarcoma-37 it has been shown that introduction of IFN and amixin significantly elevated efficacy
of vaccine therapy, in particular index of tumor growth inhibition reach 89.2% and 81.7%. Upon combined use of CV and IFN or CV and
amixin (25 mg/kg) respectively. Significant prolongation of average life span of the animals treated with CV and IFN or CV and amixin
(25 mg/kg) has been registered (up to 92.7 ± 10.4 and 95.0 ± 6.2 days respectively, vs 46.8 ± 1.5 days for control animals). Conclusion:
Obtained results have shown expediency of the development of schemes for combined introduction of CV with exogenous IFN, and with
inducer of endogenous IFN (amixin) for elevation of efficacy of vaccine therapy.
Key Words: cancer vaccine, interferon, amixin, experimental tumor, immunologic index.
Received: March 5, 2008.
*Correspondence: Fax: +38 (044) 258-16-56
E-mail: iris@onconet.kiev.ua
Abbreviations used: ALS — average life span; CIC — circulating
immune complex; CV — cancer vaccine; IFN — interferon; TGI —
tumor growth inhibition.
Exp Oncol 2008
30, 4, 319–323
320 Experimental Oncology 30, 319–323, 2008 (December)
Experimental protocols and procedures were aproved
by the Ethical Committee of IEPOR.
Table 1. Therapeutic experiment scheme for a study of efficacy of
combined use of CV and IFN or CV and amixin in sarcoma-37-bearing mice
Group Treatment Scheme of administration
CV IFN or amixin
1 CV By 0.3 ml; s/c; 5-times;
at days 1, 4, 8, 12 and 15
—
2 IFN — By 1000 U., 5-times; i/p;
at days 1,3,7, 11 and 14
3 CV + IFN By 0.3 ml; s/c; 5-times;
at days 1, 4, 8, 12 and 15
By 1000 U, 5- times; i/p;
at days 1,3,7, 11 and 14
4 Amixin
(10 mg/kg)
— By 10 mg/kg in 0.5 ml PS;
per os, 2 h prior to CV
5 CV + amixin
(10 mg/kg)
By 0.3 ml, s/c; 5-times;
at days 1, 4, 8, 12 and 15
By 10 mg/kg in 0.5 ml PS;
per os, 2 h prior to CV
6 Amixin
(25 mg/kg)
— By 10 mg/kg in 0.5 ml PS;
per os, 2 h prior to CV
7 CV + amixin
(25 mg/kg)
By 0.3 ml, s/c; 5-times;
at days 1, 4, 8, 12 and 15
By 25 mg/kg in 0.5 ml PS;
per os, 2 h prior to CV
8 Control of
trans plantation
— —
Preparation of murine IFN kindly gifted by Dr. Kudrya
vets was administered 5 times intraperitoneally by
1000 U in 0.5 ml physiologic solution (PS) 24 h prior to
CV introduction. Substance of amixin was supplied by
OSS “Interkhim”, preparation was administered p.o.
5 times at the doses of 0 mg/kg or 25 mg/kg in 0.5 ml,
2 h prior to CV administration. The animals from control
group received PS in equal manner and time points.
Efficacy of treatment was evaluated by common
tumor growth characteristics, survival and average life
span (ALS) of control and experimental animals.
Immunological studies were performed at days 14,
30 and 40 after tumor transplantation, and include deter
mination of the content of circulating immune complexes
(CIC) isolated by precipitation with PEG6000, and analysis
of the level of specific IgG antibodies in blood serum by
immunoenzyme reaction [20]. Production of IFN was
evaluated by titration of blood serum for its ability to inhibit
cytopathogenic action of vesicular stomatitis virus [21].
Significance of the differences between the para
meters was evaluated by Student’s tcriterium [22]. Cal
culations were done using Microsoft Excel program.
RESULTS AND DISCUSSION
Analysis of growth dynamics of sarcoma37 in the
groups of animals treated with studied preparation has
demonstrated its significant inhibition (Fig. 1). For exam
ple, in animals that received IFN or amixin at monoregi
men, tumor growth inhibition (TGI) index was in a range
65–75%, but the difference between experimental
groups was insignificant (p > 0.05) (Fig.1, a). Respective
index in mice treated with CV was 81.2% (Fig. 1, b).
Upon application of combined scheme of introduction
of studied preparations, the best results were observed in
mice that received CV and IFN: TGI was equal to 89.2%.
Combined introduction of CV with amixin was also effec
tive, if amixin was introduced at the dose of 25 mg/kg:
TGI was 81.7%. The results of combined use of CV with
10 mg/kg amixin were more worse then in the case of sep
arate administration of CV or amixin (TGI = 53.8%, 81.2%
and 66.5%, respectively; p < 0.05). It seems that lowdose
amixin caused even antagonistic effect in its combination
with CV. The mechanisms of such effect should be clarified.
0
1
2
3
4
5
6
7 12 15 19 22 26 29 33 36 41
Days
Tu
m
or
v
ol
um
e,
ñ
m
3
IFN
Amixin 10 mg/kg
Amixin 25 mg/kg
Control
0
1
2
3
4
5
6
7 12 15 19 22 26 29 33 36 41
Days
Tu
m
or
v
ol
um
e,
c
m
3
CV
CV + IFN
CV + amixin 10 mg/kg
CV + amixin 25 mg/kg
Control
a
b
Fig. 1. Dynamics of tumor growth in sarcoma37bearing mice treated
with IFN or amixin at monoregimen (a) or in combination with CV (b)
The studied preparations possess different effect
on efficacy of sarcoma37 transplantation (Fig. 2, a).
a
b
0
10
20
30
40
50
60
70
80
90
100
0 7 12 15 19 22 26 29 33 36 41
Days
%
m
ic
e
w
ith
tu
m
or
s
IFN
Amixin 10 mg/kg
Amixin 25 mg/kg
Control
0
10
20
30
40
50
60
70
80
90
100
0 7 12 15 19 22 26 29 33 36 41
Days
%
m
ic
e
w
ith
tu
m
or
s
CV
CV + IFN
CV + amixin 10 mg/kg
CV + amixin 25 mg/kg
Control
Fig. 2. Efficacy of sarcoma37 cells transplantation into animals treated
with IFN or amixin at monoregimen (a) or in combination with CV (b)
At day 12, all animals from control group develop
tumors, but introduction of IFN or amixin at the doses
of 25 and 10 mg/kg caused retardation of this process
(at the day 12 indexes of transplantation were 57.1;
50.0 and 37.5%, respectively), however later the tumors
developed in all animals. In particular, in mice treated
with amixin at both doses, the tumors developed at the
Experimental Oncology 30, 319–323, 2008 (December) 321
day 41. Introduction of CV resulted in decreased transp
lantation efficacy in all experimental groups (Fig. 2, b).
In CVtreated mice this index decreased to 62.5%, and
in animals treated with combination of CV with IFN or
amixin transplantation efficacy was 75%.
Animal survival rate (Fig. 3) was elevated in all experi
mental groups: while in control group all animals die be
fore day 54, in IFNtreated mice this index was 71 days,
and only 62.5% animals died at day 84, if both doses
of amixin were used. The highest survival has been
recorded in mice treated with combination of CV with
IFN or amixin (25 mg/kg) — at day 84, only 25% animals
dies in each group, and such index was significantly
higher compared to the use of CV at monoregimen or
with amixin at low dose (62.5% in each case).
a
b
0
10
20
30
40
50
60
70
80
90
100
29 33 36 41 46 49 54 58 62 67 71 75 84
Days
%
s
ur
vi
ve
d
an
im
al
s
IFN
Amixine
Amixine
Control
0
10
20
30
40
50
60
70
80
90
100
29 33 36 41 46 49 54 58 62 67 71 75 84
Days
%
s
ur
vi
ve
d
an
im
al
s
CV
CV + IFN
CV + amixin 10 mg/kg
CV + amixin 25 mg/kg
Control
Fig. 3. Survival of sarcoma37bearing animals treated with IFN
or amixin at monoregimen (a) or in combination with CV (b)
Analysis of ALS (Table 2) was in agreement with these
observations: the best results were registered exactly upon
combined use of CV and IFN or CV with 25mg/kg amixin
(ALS indexes were 92.7 ± 10.4 and 95.0 ± 6.2 days vs
46.8 ± 1.5 days in control group, p < 0.05). These indexes
were significantly higher than these for separate use of
each preparation (ALS indexes in mice treated with CV,
IFN or 25 mg/kg amixin at monoregimen were 79.3 ± 10.9,
64.7 ± 10.1, and 79.0 ± 5.9 days, respectively). So, above
mentioned data allow state elevation of efficacy of CV upon
its combined use with IFN or amixin. Decreased amixin
dose (10 mg/kg) introduced into combined scheme did
not cause such effect: ALS did not differ significantly
from that for separate introduction of (77.0 ± 7.8 vs
77.0 ± 10.1 days, р > 0.05), but was significantly higher
than ALS in control group (р < 0.05).
Determination of IFN titers in blood serum of
experimental animals did not reveal the peculiari
ties explaining clearly the different efficacy of used
schemes of IFN or amixin administration (Table 3).
Compared to the control group, in all experimental
groups there was observed elevation of IFN titers at
day 14 and especially at day 30 of tumor growth, and its
decrease at day 40. In control tumor bearing animals
these indexes were 1 : 64; 1 : 64; 1 : 16 respectively.
Table 2. Average life span of sarcoma-37-bearing mice treated with
IFN or amixin at monoregimen or in combination with CV
Group Treatment Number
of animals
ALS
Х ± m t MI%
1 CV 8 79.3 ± 10.9 2.93 69.4
2 IFN 8 64.7 ± 10.1 1.73 38.2
3 CV + IFN 8 92.7 ± 10.4 4.31 98.0
4 CV + amixin 10 mg/kg 8 77.0 ± 7.8 3.79 64.5
5 Amixin 10 mg/kg 8 77.0 ± 10.1 3.04 66.8
6 CV + amixin 25 mg/kg 8 95.0 ± 6.2 7.56 102.9
7 Amixin 25 mg/kg 8 79.0 ± 5.9 5.32 68.8
8 Control 8 46.8 ± 1.5
Table 3. IFN titers in blood serum of sarcoma-37-bearing mice treated
with IFN or amixin at monoregimen or in combination with CV
Group Treatment Days after tumor transplantation
14 30 40
1 CV 1 : 128 1 : 128 1 : 16
2 IFN 1 : 32 1 : 16 1 : 16
3 CV + IFN 1 : 32 1 : 64 1 : 64
4 CV + amixin 10 mg/kg 1 : 64 1 : 128 1 : 32
5 Amixin 10 mg/kg 1 : 64 1 : 256 1 : 32
6 CV + amixin 25 mg/kg 1 : 64 1 : 256 1 : 32
7 Amixin 25 mg/kg 1 : 64 1 : 128 1 : 16
8 Control 1 : 64 1 : 64 1 : 16
9 Intact animals 1 : 16 1 : 16 1 : 16
Using immunoenzyme assay (IEA) we have deter
mined the level of sarcoma37 antigens in blood serum
of experimental animals (Fig. 4). The results evidence
on significant increase of this index in control animals
during all terms of observation, even at late stages of
tumor growth, however, in mice treated with IFN or CV at
monoregimen or in combination, the level of antitumor
antibodies was higher, pointing on immunostimulating
action of the preparations. The use of amixin at the dose
of 25 mg/ml in both schemes significantly decreased this
index compared to the control. In contrary, introduction
of lowdose amixin resulted in the level of antibodies at
days 30–40 of tumor growth close to control values, while
its combined use with CV also leads to sharp decrease of
IgG levels at the late terms of tumor development.
The study of content of mediummolecular weight
CIC in blood of control tumorbearing group has shown
its elevation compared to intact animals, as well as its
drastic increase (up to 0.777 ou.) at late stages of tumor
growth (Fig. 5). Upon administration of IFN, the dynam
ics of CIC content seems to be similar to that of intact
animals, except its low value (0.183 ou.) at day 14 of
tumor growth. At day 14 similarly low level of CIC has
been detected also in the case of CV administration
(at monoregimen or in combination with IFN), but in
this case at day 40, sharp decrease of CIC level was
observed after elevation of this index at day 30 charac
teristic for the majority of experimental groups.
In contrary, introduction of amixin was accompanied
with elevation of CIC level at day 14 of tumor growth
(0.520–0.540 ou), close to this index in the group of
tumorbearing control animals. However, at day 40, CIC
level has been decreasing fluently (25 mg/ml dose), or
sharply (10 mg/ml dose). Combined use of amixin and CV
also leads to sharp decrease of CIC content in blood serum
322 Experimental Oncology 30, 319–323, 2008 (December)
at respective time point. It is necessary to note that at late
terms after tumor transplantation (day 40) in mice treated
with CV or amixin by different schemes, sharp decrease
of this index has been registered compared to control ani
mals; according to the data of literature, such effect point
on favorable prognosis of the disease [23, 24]. In our study
it was accompanied by significant tumor growth inhibition
and elevation of life span of vaccinated animals.
a
b
0
0.5
1
1.5
2
2.5
3
3.5
14 30 40
Days
IE
A
in
de
x
IFN Amixin 10 mg/kg
Amixin 25 mg/kg Control
Intact
0
0.5
1
1.5
2
2.5
3
3.5
14 30 40
Days
IE
A
in
de
x
CV CV + IFN
CV + amixin 10 mg/kg CV + amixin 25 mg/kg
Control
Fig. 4. IgG levels in blood serum of sarcoma37bearing mice treated
with IFN or amixin at monoregimen (a) or in combination with CV (b)
a
b
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
14 30 40
Days
Ex
tin
ct
io
n
va
lu
e,
4
50
n
m
IFN Amixin 10 mg/kg
Amixin 25 mg/kg Control
Intact
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
14 30 40
Days
Ex
tin
ct
io
n
va
lu
e,
4
50
n
m
CV CV + IFN
CV + amixin 10 mg/kg
CV + amixin 25 mg/kg
Control
Fig. 5. CIC levels in sarcoma37bearing mice treated with IFN
or amixin at monoregimen (a) or in combination with CV (b)
In conclusion, above mentioned results have de
monstrated that inducer of synthesis of endogenous
IFN amixin at a dose of 25 mg/kg as well as exogenous
IFN at a dose of 1000 U are able to elevate equally an
ticancer action of the vaccine. Our data evidence on
possibility for improvement of efficacy of cancer vaccine
via development of combined schemes for its use.
ACKNOwLEDGEMENTS
We wish to express our gratitude to Dr. Yu.I. Kug
ryavets (IEPOR NASU, Kyiv, Ukraine) for kindly gifted
murine IFN, and to colleagues from Department of
the Problems of Interferon and Immunomodulators of
D.K. Zabolotny Institute of Microbiology and Virology
NASU (Kyev, Ukraine) for determination of IFN titers
in blood serum of experimental animals.
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ПОВЫШЕНИЕ ЭФФЕКТИВНОСТИ ПРОТИВООПУХОЛЕВОЙ
ВАКЦИНЫ ИНТЕФЕРОНОМ И ИНДУКТОРОМ СИНТЕЗА
ЭНДОГЕННОГО ИНТЕРФЕРОНА — АМИКСИНОМ
Цель: изучить в эксперименте эффективность комбинированной схемы введения противоопухолевой вакцины (CV) с интер-
фероном (ИФН) и индуктором эндогенного ИФН — амиксином. Материалы и методы: саркому-37 трансплантировали
мышам-самкам Balb/c. Для лечения использовали CV, приготовленную из клеток саркомы-37 с помощью цитотоксиче-
ских лектинов B. subtilis B-7025, мышиный ИФН (1000 ед.) и амиксин (10 и 25 мг/кг). Иммунологические исследования
включали определение в сыворотке крови титров ИФН, количества циркулирующих иммунных комплексов и уровня
специфических противоопухолевых IgG-антител. Результаты: на модели солидной формы саркомы-37 показано, что
применение ИФН и амиксина достоверно способствует повышению результатов вакцинотерапии, а именно, при комби-
нированном использовании CV и ИФН индекс торможения опухолевого роста (ИТО) достигал 89,2%; при сочетании CV
и амиксина (25 мг/кг) ИТО составил 81,7%. Зарегистрировано существенное увеличение средней продолжительности
жизни животных, получивших CV с ИФН или амиксином (25 мг/кг), до 92,7 ± 10,4 и 95,0 ± 6,2 сут соответственно, по
сравнению с такой контрольных мышей (46,8 ± 1,5 сут, p < 0,05). Выводы: полученные результаты свидетельствуют о
перспективности разработки комбинированных схем введения CV как с препаратом экзогенного ИФН, так и с индуктором
эндогенного ИФН (амиксин), что позволяет повысить эффективность вакцинотерапии.
Ключевые слова: противоопухолевая вакцина, интерферон, амиксин, экспериментальная опухоль, показатели иммунитета.
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