Experimental study of the efficacy of combined use of cancer vaccine and interferon
Aim: To study in in vivo model the efficacy of combined scheme of administration of cancer vaccine (CV) and interferon (IFN). Materials and Methods: Lewis lung carcinoma (LLC) was transplanted to male C57Bl mice. For treatment, CV prepared from LLC cells with the use of cytotoxic lectins of B. subti...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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| Zitieren: | Experimental study of the efficacy of combined use of cancer vaccine and interferon / G.P. Potebnya, Yu.Y. Kudryavets, G.S. Lisovenko, N.L. Cheremshenko, I.M. Voeykova, N.V. Trokhimenko, T.V. Symchich, L.M. Evstrateyva // Experimental Oncology. — 2007. — Т. 29, № 2. — С. 102–105. — Бібліогр.: 23 назв. — англ. |
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Potebnya, G.P. Kudryavets, Yu.Y. Lisovenko, G.S. Cheremshenko, N.L. Voeykova, I.M. Trokhimenko, N.V. Symchich, T.V. Evstrateyva, L.M. 2018-06-19T09:50:46Z 2018-06-19T09:50:46Z 2007 Experimental study of the efficacy of combined use of cancer vaccine and interferon / G.P. Potebnya, Yu.Y. Kudryavets, G.S. Lisovenko, N.L. Cheremshenko, I.M. Voeykova, N.V. Trokhimenko, T.V. Symchich, L.M. Evstrateyva // Experimental Oncology. — 2007. — Т. 29, № 2. — С. 102–105. — Бібліогр.: 23 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/138575 Aim: To study in in vivo model the efficacy of combined scheme of administration of cancer vaccine (CV) and interferon (IFN). Materials and Methods: Lewis lung carcinoma (LLC) was transplanted to male C57Bl mice. For treatment, CV prepared from LLC cells with the use of cytotoxic lectins of B. subtilis B-7025, and preparation of murine IFN-alpha were used. Therapeutic effect was evaluated by measurement of tumor volume and analysis of average life span (ALS) of treated animals. Immunologic study included determination of antitumor cytotoxicity of T-lymphocytes (CTL) and natural killer (NK) cells by radiometric method, functional activity of peritoneal macrophages (MP) — by colorimetric test with nitroazole blue, and evaluation of titers of tumor necrosis factor (TNF) and interleukins-1 and -2 (IL-1, 2). Results: It has been shown that the use of IFN preparation significantly elevated efficacy of vaccine therapy of solid form of LLC: duration of latent period of tumor growth elevated by 25%, ALS — by 28%, index of tumor growth inhibition — by 35–40%. Upon combined use of CV and IFN, significant activation of the cells — effectors of nonspecific immune defense (MP), and specific one (CTL) was observed. Conclusion: The obtained results evidence on perspectiveness of the development of combined schemes of administration of CV and IFN for elevation of the efficacy of vaccine therapy. Цель: исследовать в эксперименте эффективность комбинированной схемы введения противоопухолевой вакцины (ПВ) и интерферона (ИФН). Материалы и методы: карциному легкого Льюис (КЛЛ) трансплантировали мышам-самцам C57Bl. Для лечения использовали ПВ, приготовленную из клеток КЛЛ с помощью цитотоксических лектинов B. subtilis B-7025, и препарат мышиного ИФН. Терапевтический эффект оценивали путем измерения объема солидной опухоли и анализа средней продолжительности жизни опытных животных. Иммунологическое исследование включало определение противоопухолевой цитотоксичности Т-лимфоцитов (ЦТЛ) и природных киллерных клеток (ПКК) радиометрическим методом; функциональной активности перитонеальных макрофагов (Мф) в колориметрическом НСТ-тесте; определение титров фактора некроза опухоли (ФНО), интерлейкинов-1 и -2. Результаты: показано, что использование препарата ИФН существенно повышает эффективность вакцинотерапии солидной формы модельной КЛЛ: на 25% повышается продолжительность латентного периода, на 28% — средняя продолжительность жизни мышей, на 35–40% — индекс торможения опухолевого роста. При комбинированном применении ПВ и ИФН отмечают существенную активацию клеток-эффекторов как неспецифической (Мф), так и специфической (ЦТЛ) иммунной защиты. Выводы: полученные результаты свидетельствуют о перспективности разработки комбинированных схем введения ПВ с ИФН, позволяющих повысить эффективность вакцинотерапии. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions Experimental study of the efficacy of combined use of cancer vaccine and interferon Экспериментальное исследование эффективности комбинированного использования противоопухолевой вакцины и интерферона Article published earlier |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| title |
Experimental study of the efficacy of combined use of cancer vaccine and interferon |
| spellingShingle |
Experimental study of the efficacy of combined use of cancer vaccine and interferon Potebnya, G.P. Kudryavets, Yu.Y. Lisovenko, G.S. Cheremshenko, N.L. Voeykova, I.M. Trokhimenko, N.V. Symchich, T.V. Evstrateyva, L.M. Original contributions |
| title_short |
Experimental study of the efficacy of combined use of cancer vaccine and interferon |
| title_full |
Experimental study of the efficacy of combined use of cancer vaccine and interferon |
| title_fullStr |
Experimental study of the efficacy of combined use of cancer vaccine and interferon |
| title_full_unstemmed |
Experimental study of the efficacy of combined use of cancer vaccine and interferon |
| title_sort |
experimental study of the efficacy of combined use of cancer vaccine and interferon |
| author |
Potebnya, G.P. Kudryavets, Yu.Y. Lisovenko, G.S. Cheremshenko, N.L. Voeykova, I.M. Trokhimenko, N.V. Symchich, T.V. Evstrateyva, L.M. |
| author_facet |
Potebnya, G.P. Kudryavets, Yu.Y. Lisovenko, G.S. Cheremshenko, N.L. Voeykova, I.M. Trokhimenko, N.V. Symchich, T.V. Evstrateyva, L.M. |
| topic |
Original contributions |
| topic_facet |
Original contributions |
| publishDate |
2007 |
| language |
English |
| container_title |
Experimental Oncology |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| format |
Article |
| title_alt |
Экспериментальное исследование эффективности комбинированного использования противоопухолевой вакцины и интерферона |
| description |
Aim: To study in in vivo model the efficacy of combined scheme of administration of cancer vaccine (CV) and interferon (IFN). Materials and Methods: Lewis lung carcinoma (LLC) was transplanted to male C57Bl mice. For treatment, CV prepared from LLC cells with the use of cytotoxic lectins of B. subtilis B-7025, and preparation of murine IFN-alpha were used. Therapeutic effect was evaluated by measurement of tumor volume and analysis of average life span (ALS) of treated animals. Immunologic study included determination of antitumor cytotoxicity of T-lymphocytes (CTL) and natural killer (NK) cells by radiometric method, functional activity of peritoneal macrophages (MP) — by colorimetric test with nitroazole blue, and evaluation of titers of tumor necrosis factor (TNF) and interleukins-1 and -2 (IL-1, 2). Results: It has been shown that the use of IFN preparation significantly elevated efficacy of vaccine therapy of solid form of LLC: duration of latent period of tumor growth elevated by 25%, ALS — by 28%, index of tumor growth inhibition — by 35–40%. Upon combined use of CV and IFN, significant activation of the cells — effectors of nonspecific immune defense (MP), and specific one (CTL) was observed. Conclusion: The obtained results evidence on perspectiveness of the development of combined schemes of administration of CV and IFN for elevation of the efficacy of vaccine therapy.
Цель: исследовать в эксперименте эффективность комбинированной схемы введения противоопухолевой вакцины (ПВ)
и интерферона (ИФН). Материалы и методы: карциному легкого Льюис (КЛЛ) трансплантировали мышам-самцам C57Bl.
Для лечения использовали ПВ, приготовленную из клеток КЛЛ с помощью цитотоксических лектинов B. subtilis B-7025,
и препарат мышиного ИФН. Терапевтический эффект оценивали путем измерения объема солидной опухоли и анализа средней
продолжительности жизни опытных животных. Иммунологическое исследование включало определение противоопухолевой
цитотоксичности Т-лимфоцитов (ЦТЛ) и природных киллерных клеток (ПКК) радиометрическим методом; функциональной
активности перитонеальных макрофагов (Мф) в колориметрическом НСТ-тесте; определение титров фактора некроза
опухоли (ФНО), интерлейкинов-1 и -2. Результаты: показано, что использование препарата ИФН существенно повышает
эффективность вакцинотерапии солидной формы модельной КЛЛ: на 25% повышается продолжительность латентного
периода, на 28% — средняя продолжительность жизни мышей, на 35–40% — индекс торможения опухолевого роста. При
комбинированном применении ПВ и ИФН отмечают существенную активацию клеток-эффекторов как неспецифической
(Мф), так и специфической (ЦТЛ) иммунной защиты. Выводы: полученные результаты свидетельствуют о перспективности
разработки комбинированных схем введения ПВ с ИФН, позволяющих повысить эффективность вакцинотерапии.
|
| issn |
1812-9269 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/138575 |
| citation_txt |
Experimental study of the efficacy of combined use of cancer vaccine and interferon / G.P. Potebnya, Yu.Y. Kudryavets, G.S. Lisovenko, N.L. Cheremshenko, I.M. Voeykova, N.V. Trokhimenko, T.V. Symchich, L.M. Evstrateyva // Experimental Oncology. — 2007. — Т. 29, № 2. — С. 102–105. — Бібліогр.: 23 назв. — англ. |
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102 Experimental Oncology 29, 102–105, 2007 (June)
To improve the technology of cancer biotherapy, it is
important to understand functions and mechanism of ac-
tion of cytokines that are involved in attraction of immuno-
competent cells to immune reactions and elevate ability
of T-lymphocytes to eliminate malignant cells. That’s why
biological modifiers of immune response are often used
in technology of preparation of cancer vaccines (CV) or
are used as their components. In the most simple variant,
cytokines are administered together with antigen and
stimulate immune response against it [1–4].
Interferon (IFN) is one of the key modulators of im-
mune response influencing the processes of antigen
recognition, differentiation, and functional activity of
immunocompetent cells. The most interesting aspects
of studies are effects of IFN related to elevation of
tumor immunogenecity and its altered sensitivity to
cytotoxic action of T-lymphocytes [5].
The role of IFN in combination with other biological
agents or chemopreparations became a subject of
intense studies. The research of effects of IFN upon
combined use with active specific immunization is of
special interest [1, 6, 7]. IFNs, including IFN-α2, -β, -γ,
are potent inducers of expression of genes of major
histocompatibility complex. Exactly this property, apart
from indirect immunomodulating action is one of the
main reasons for use of IFN in immunotherapy [8]. The
facts on high anticancer acitivity of IFN in the case of
metastatic melanoma and the increasing number of
reports about positive influence of this cytokine on
elongation of relapse-free period in the patients after
tumor resection are evidencing the expediency of
combined use of IFN with CV [6, 9, 10]. The mecha-
nisms of synergistic action of vaccine and IFN possibly
will differ dependent on composition of the vaccine
and the immune reactions that provide an effect of
immunization. In numerous reports it has been shown
that IFN-α possesses the highest anticancer action [5,
6, 8]. The results of experimental and clinical studies
are providing the grounds for the use of IFN-α as an
element of optimization of combined therapy directed
on the decrease of metastasis risk and improvement
of quality of life of oncological patients [10, 11].
The aim of present research was to evaluate the
possibilities of the use of immunomodulating properties
of IFN for elevation of the efficacy of cancer vaccine
prepared from autologous tumor cells with the use of
cytotoxic lectin (CL) from B. subtilis B-7025 [12, 13].
MATERIALS AND METHODS
The experiments were carried out on male С57Вl
2.5 months old mice bred in the vivarium of R.E. Ka-
vetsky Institute of Experimental Pathology, Oncology
and Radiobiology NAS of Ukraine (Kyiv, Ukraine) with
the use of experimental model of Lewis lung carci-
noma (LLC). Tumor cells were transplanted in the
thigh muscle (by 5.0 х 105 vital LLC cells per animal).
The animals were treated by therapeutic scheme as
follow: 1st group received CV, 2nd – preparation of mu-
rine IFN, 3rd — CV + IFN by combined scheme. In this
series of experiments, the group of untreated animals
(4th group, transplantation control) and intact animals
(5th group) served as the controls. All experiments with
animals were approved by local ethic committee.
CV was prepared from grounded LLC tissue
samples treated with cytotoxic lectins of В. subtilis
B-7025 (1 g of tumor tissue per 10 ml CL solution
(0.5 mg/ml)) and stored at –18 ˚С [12]. Preparation
of CL was isolated from culture medium of В. subtilis
B-7025 by the method described earlier [14]. CV was
EXPERIMENTAL STUDY OF THE EFFICACY OF COMBINED USE
OF CANCER VACCINE AND INTERFERON
G.P. Potebnya*, Yu.Y. Kudryavets, G.S. Lisovenko, N.L. Cheremshenko,
I.M. Voeykova, N.V. Trokhimenko, T.V. Symchich, L.M. Evstrateyva
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine
Aim: To study in in vivo model the efficacy of combined scheme of administration of cancer vaccine (CV) and interferon (IFN).
Materials and Methods: Lewis lung carcinoma (LLC) was transplanted to male C57Bl mice. For treatment, CV prepared from LLC
cells with the use of cytotoxic lectins of B. subtilis B-7025, and preparation of murine IFN-alpha were used. Therapeutic effect was
evaluated by measurement of tumor volume and analysis of average life span (ALS) of treated animals. Immunologic study included
determination of antitumor cytotoxicity of T-lymphocytes (CTL) and natural killer (NK) cells by radiometric method, functional
activity of peritoneal macrophages (MP) — by colorimetric test with nitroazole blue, and evaluation of titers of tumor necrosis factor
(TNF) and interleukins-1 and -2 (IL-1, 2). Results: It has been shown that the use of IFN preparation significantly elevated efficacy
of vaccine therapy of solid form of LLC: duration of latent period of tumor growth elevated by 25%, ALS — by 28%, index of tumor
growth inhibition — by 35–40%. Upon combined use of CV and IFN, significant activation of the cells — effectors of nonspecific
immune defense (MP), and specific one (CTL) was observed. Conclusion: The obtained results evidence on perspectiveness of the
development of combined schemes of administration of CV and IFN for elevation of the efficacy of vaccine therapy.
Key Words: cancer vaccine, murine interferon, Lewis lung carcinoma, immunologic indexes.
Received: March 28, 2007.
*Correspondence: E-mail: iris@onconet.kiev.ua
Abbreviations used: CTL — cytotoxic lymphocytes; CV — cancer
vaccine; IFN — interferon; IL-1 — interleukin-1; LI — labeling in-
dex; LLC — Lewis lung carcinoma; MP — peritoneal macrophages;
NK — natural killer cells; TNF — tumor necrosis factor.
Exp Oncol 2007
29, 2, 102–105
Experimental Oncology 29, 102–105, 2007 (June) 10329, 102–105, 2007 (June) 103June) 103) 103 103
injected subcutaneously (s. c.) by 0.3 ml at the days
1, 4, 8, 11, 15 after LLC transplantation.
Preparation of IFN-alpha was prepared according
to [15]. IFN solution was prepared ex tempore and ad-
ministered 5 times intraperitoneally (i.p.) by 1000 units
in 0.5 ml of physiologic solution 24 h prior to CV ad-
ministration. Such scheme for IFN administration was
chosen of the base of results of studies on combined
use of CV with other immunomodulating preparations
[16, 17]. Efficacy of treatment was evaluated by tumor
growth inhibition index and average life span (ALS) of
experimental animals.
Immunologic research included determination of
cytotoxic activity of T-lymphocytes (CTL) and natural
killer (NK) cells in cytotoxic tests in vitro [18], cyto-
chemical activity of peritoneal macrophages (MP)
using test with nitroazole blue (NBT) [19], the level
of production of tumor necrosis factor (TNF) by
MP in vitro using TNF-sensitive L-929 cells [20], the
levels of production of IL-1 by adherent fraction of
spleen lymphocytes, and IL-2 — by nonadherent one
using standard radiometric methods [21, 22]. These
studies were carried out at the days 28 and 45 after
tumor cells transplantation.
Statistical analysis was carried out using Student’s
t-criterium; the values p < 0.05 were considered sig-
nificant [23].
RESULTS AND DISCUSSION
The study of LLC growth evidenced on significant
increase of the duration of latent period and pronounced
inhibition of tumor growth upon combined use of CV and
murine IFN compared with these indexes in the groups of
transplantation control or upon separate use of CV and IFN
(Fig. 1). Analogous peculiarities have been registered dur-
ing analysis of ALS of experimental animals (Table 1). In the
group of LLC-bearing mice that received CV at monoregi-
men (group 1), insignificant increase of the duration of
latent period has been observed as well as tumor growth
inhibition by 24–45%, that lead to significant increase of
ALS. Administration of CV with IFN (group 3) led to signifi-
cant increase of its efficacy: the duration of latent period
elevated by 25%, whilst tumor growth inhibition increased
by 35–40%. ALS indexes in groups 1 and 3 were 53.71 ±
4.0 and 65.0 ± 2.9 days respectively (p < 0.05). It should
be stressed that upon separate use murine IFN also was
effective compared to control indexes: the duration of
latent period elevated by 39%, ALS — by 38% (54.8 ±
3.75 and 39.8 ± 1.8 days respectively, p < 0.05). So, the
obtained results have shown that aadministration of IFN
to LLC-bearing mice at monoregimen or in combination
with vaccine elevates vaccine’s efficacy.
The study of immunologic indexes allowed to anali-
ze their changes in treated animals (Table 2). In control
group of LLC-bearing mice at the day 28 the cytotoxic
activity of NK cells and CTL has been restored at relatively
high level (labeling index (LI) was +322.6% and +196.0%,
respectively compared to intact control). These indexes
as well as MP activity (LI = +79.4%) were significantly
higher than these of intact animals (p < 0.05).
Fig. 1. Duration of latent period (a) and tumor growth inhibition
of experimental animals
*p < 0.05 compared to control of transplantation.
Table 1. Average life span (ALS) and duration of latent period in mice
bearing Lewis lung carcinoma
Group Treat-
ment
Number
of ani-
mals
ALS, days Latent period, days
Х ± m t LI, % Х ± m t LI, %
I CV 14 53.7 ± 4.0 2.8* 35.0 11.1 ± 1.3 1.4 13.5
ІІ IFN 15 54.8 ± 3.8 3.1* 37.7 12.5 ± 1.1 2.5* 28.3
ІІI CV + IFN 11 65.0 ± 3.9 5.8* 63.3 13.5 ± 1.6 2.7* 38.2
ІV Control 10 39.8 ± 1.8 – – 9.0 ± 0.8 – –
*p < 0.05 compared to control of transplantation.
Table 2. Activity of effectors of cellular antitumor immunity in mice
bearing Lewis lung carcinoma (day 28 of tumor growth)
Group Treatment CI, % Activity of MP
in NBT-testNK CTL
I CV 43.2 ± 2.3*, ** 7.8 ± 4.5*** 0.176***
ІІ IFN 9.4 ± 4.7*** 28.0 ± 4.3* 0.243
IІІ CV + IFN 10.6 ± 5.2*** 34.6 ± 2.4* 0.600*, ***
ІV Control of transplantation 35.5 ± 2.6* 24.5 ± 13.8* 0.393*
V Intact control 6.4 ± 2.0 2.0 ± 1.2 0.219
*р < 0.05 compared to intact control;
**0.05 < р < 0.1 compared to control of transplantation;
***р < 0.05 compared to control of transplantation.
Administration of CV to mice resulted in the marked
NK cells activation (43.2 ± 2.3 versus 35.5 ± 2.6% for
group of transplantation control, p < 0.05); at the same
time the indexes of activities of CTL and MP remained
at the level of intact control and were significantly
lower than these of transplantation control group.
Upon the use of IFN, the situation was different — the
preparation acted mainly via activation of CTL. Com-
bined treatment with both agents (CV + IFN) along by
increased specific response was accompanied with
elevation of MP activity (compared to transplantation
control group, LI was +41% and +52,7%, respectively,
p < 0.05), whilst NK cells cytotoxicity remained at the
level of that of intact animals.
It is known that along with effectors of specific and
natural resistance, cytokines (IL-1, IL-2, TNF, IFN) play
104 Experimental Oncology 29, 102–105, 2007 (June)
an important role in anticancer defense of the body.
As biologic modifiers of immune response, they are
often used in technology of preparation of cancer vac-
cines or are used as their components. That’s why one
may suppose that positive effects of vaccine therapy
combined with IFN could be in part explained by its
influence on the level of production at least some of
mentioned cytokines, in particular, TNF, IL-1, IL-2.
At the day 28 of tumor growth, production of TNF
in animals from transplantation control group was de-
creased compared with intact control: this is evidenced
by relatively low titer of TNF (LI = –51.9%, р < 0.05)
(Table 3). It should be noted that at this time point in
experimental groups (groups І–ІІІ) production of TNF
remained at the level of intact animals only in mice
that received IFN (the titer of TNF activity in this group
was 2.55 ± 0.25 log2 and was twice higher than such
indexes of transplantation control group as well as other
experimental groups. At this period no alterations in IL-1
activity have been observed in all studied groups.
Level of IL-2 production in the supernatants of cul-
tured lymphocytes isolated at day 28 from the animals
of transplantation control group was significantly lower
than that of intact animals (LI = –56.8%, р < 0.05). At
this period in mice from groups І and ІІ the titer of IL-2І and ІІ the titer of IL-2 and ІІ the titer of IL-2ІІ the titer of IL-2 the titer of IL-2
activity was practically equal to that of tumor-bearing
control mice (LI was –35% and –16%, respectively,
compared to transplantation control group). The titers
of IL-2 activity in mice that received IFN + CV were close
to these of intact control (LI = –36% compared to in-
tact control, and +46.8% compared to transplantation
control group) (Table 4). It’s interesting that exactly in
this group the highest percent of animals (25%) that
didn’t develop tumors has been registered.
Table 4. Production of IL-2* by Т-lymphocytes from spleen of С57Bl mice
after transplantation of Lewis lung carcinoma cells
Group of animals Activity of
CTL, CI, %
Terms of observation (days after
tumor cell transplantation)
28 45
CV 7.8 ± 4.52 < 1 log2
1, 2 –
CV + IFN 34.6 ± 2.41 2.26 ± 0.011, 2 2.68 ± 0.071, 3
IFN 28.0 ± 4.31 1.29 ± 0.011, 2 –
Control of transplantation 24.5 ± 3.81 1.54 ± 0.11 –
Intact control 2.0 ± 1.2 3.57 ± 0.08
*Production of IL-2 is expressed in titres of activity, log2;
1p < 0.05 compared to intact control; 2p < 0.05 compared to control of
transplantation; 3p < 0.05 compared to previous observation point.
That’s why it looks reasonable to analyze the state
of effectors of anticancer defense (CTL, NK, MP)
(Fig. 2) in these animals. Immunologic research has
been carried out at day 45 after LLC transplantation (at
this term all animals from transplantation control group
died, ALS = 39.8 ± 1.8 days). The results have shown
significant activation of effector cells of specific and
unspecific defense (p < 0.05). At this term of observa-
tion the highest CTL activity has been registered in mice
that received IFN separately or in combination with CV
(LI was +993.0% and +615.6% respectively, p < 0.05,
compared to intact animals). The indexes of NK and MP
activity in mice of experimental groups were similar and
were significantly higher than control ones.
Fig. 2. Activity of effectors of cell immunity in mice with unde-
veloped tumors (day 45 after LLC transplantation), that received
CV + IFN by combined scheme: a — cytotoxicity of NK and CTL,
b — activity of MP in NBT-test.
In conclusion, the presented data allow suppose
that the use of IFN at monoregimen or in combination
with CV favors restoraton of the functional reserve of
all effectors of antitumor defense of the body, and
that combined administration of CV and IFN could be
considered as a promising tool. Further exploration
of synergistic action of these preparations could be
useful for the development of effective schemes of
biotherapy of oncologic diseases.
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Table 3. Production of TNF and IL-1 in vitro by adherent splenocytes of mice bearing Lewis lung carcinoma that received CV + IFN by combined scheme
Cyto-
kine Group Titer of activity,
log2
Cytotoxicity index, %
1 : 2 1 : 4 1 : 8 1 : 16 1 : 32 1 : 64
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ЭКСПЕРИМЕНТАЛЬНОЕ ИССЛЕДОВАНИЕ ЭФФЕКТИВНОСТИ
КОМБИНИРОВАННОГО ИСПОЛЬЗОВАНИЯ
ПРОТИВООПУХОЛЕВОЙ ВАКЦИНЫ И ИНТЕРФЕРОНА
Цель: исследовать в эксперименте эффективность комбинированной схемы введения противоопухолевой вакцины (ПВ)
и интерферона (ИФН). Материалы и методы: карциному легкого Льюис (КЛЛ) трансплантировали мышам-самцам C57Bl.
Для лечения использовали ПВ, приготовленную из клеток КЛЛ с помощью цитотоксических лектинов B. subtilis B-7025,
и препарат мышиного ИФН. Терапевтический эффект оценивали путем измерения объема солидной опухоли и анализа средней
продолжительности жизни опытных животных. Иммунологическое исследование включало определение противоопухолевой
цитотоксичности Т-лимфоцитов (ЦТЛ) и природных киллерных клеток (ПКК) радиометрическим методом; функциональной
активности перитонеальных макрофагов (Мф) в колориметрическом НСТ-тесте; определение титров фактора некроза
опухоли (ФНО), интерлейкинов-1 и -2. Результаты: показано, что использование препарата ИФН существенно повышает
эффективность вакцинотерапии солидной формы модельной КЛЛ: на 25% повышается продолжительность латентного
периода, на 28% — средняя продолжительность жизни мышей, на 35–40% — индекс торможения опухолевого роста. При
комбинированном применении ПВ и ИФН отмечают существенную активацию клеток-эффекторов как неспецифической
(Мф), так и специфической (ЦТЛ) иммунной защиты. Выводы: полученные результаты свидетельствуют о перспективности
разработки комбинированных схем введения ПВ с ИФН, позволяющих повысить эффективность вакцинотерапии.
Ключевые слова: противоопухолевая вакцина, интерферон, карцинома легкого Льюис, иммунные показатели.
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