JPWO2006038527A1 - Anti-tumor immunostimulant containing tamogi mushroom extract as active ingredient - Google Patents

Abstract

Disclosed is an antitumor immunostimulant containing a potato extract as an active ingredient. It has been shown that the bamboo shoot extract suppresses the growth of tumor cell cells, enhances the production of immunostimulatory cytokines, and suppresses the increase in immunosuppressive T cells. The present invention also provides an immune-stimulated health food comprising a bamboo shoot extract and a health food for suppressing tumor cell growth.

Description

  The present invention relates to an antitumor immunostimulant and an immunostimulatory health food containing a potato extract as an active ingredient.

  Various reports have been made on the bioimmunity-stimulating action of mushrooms, and the mechanism of immunostimulation and the difference in physiological activity due to the difference in mushroom species have been gradually clarified. So far, polysaccharides contained in certain types of mushrooms have been commercialized and used for anti-cancer purposes, but their effects are not always sufficient, and more useful immunostimulators are desired. It was.

  In recent years, therapeutic methods using drugs for various infectious diseases and cancers have been developed and their usefulness has been found, but satisfactory results have not been obtained for cancer chemotherapy and cancer immunotherapy. The onset of these diseases is largely due to decreased activity of immunocompetent cells. Therefore, a composition having an immunostimulatory effect on immunocompetent cells is extremely useful for the prevention and treatment of these diseases, and is also important from the viewpoint of maintaining health.

  The host defense mechanism by the immune system includes innate immunity and acquired immunity. Innate immunity is a mechanism in which macrophages and leukocytes are the main components that eliminate patterns from the living body by recognizing and preying on patterns of pathogenic bacteria, while acquired immunity is a variety of foreign substances mainly consisting of T cells and B cells. It is an immune response that can respond to each antigen. The immune response reacts as powerfully and efficiently as the living body is exposed to the antigen, and protects against reinfection of viruses and the like. However, it has been shown that inflammatory tissue damage and autoimmune diseases occur frequently when the immune response is constantly active in the body, and the immune response is negatively controlled in the body. Cells, i.e., suppressor T cells, are naturally involved in maintaining autoimmune tolerance in normal individuals.

  Recent studies have shown that abnormal suppressor T cells are a direct cause of human autoimmune diseases, inflammatory bowel disease, and allergies. If the function of this suppressor T cell can be strengthened, it can be expected to control autoimmune diseases, allergies, and immune rejection to transplanted organs.

  On the other hand, it has been shown that inhibitory T cells inhibit an effective immune response against tumor cells (cancer cells) generated from self in normal individuals. That is, it is considered that cells involved in autoimmune tolerance are also tolerant to tumor cells. Actually, when inhibitory T cells are experimentally removed from a normal individual, an immune response to the tumor is induced or enhanced, and an antitumor effect can be exerted.

  Inhibitory T cells present in normal individuals are classified as CD25 or GITR (Glucocorticoid-induced TNFR family gene) and FoxP3 gene positive cells contained in the CD4 positive T cell group. Therefore, inhibitory T cells present in lymphoid tissues (spleen, lymph nodes, peripheral blood, bone marrow) in normal individuals can be analyzed with CD4 and CD25, GITR or FoxP3 molecule-positive cells. When the ratio of inhibitory T cells is increased in vivo, the individual is likely to be immunotolerant or immunosuppressed, and the immune response against tumors, viruses, pathogenic bacteria, etc. is also reduced.

  Therefore, an immunomodulator that can suppress the increase of immunosuppressive T cells is considered useful as an active ingredient of an immunostimulator.

  Prior art document information relating to the present invention includes the following: JP-A-11-302191, and Asahi Misaki et al., “Chemical Properties and Antitumor Action of Polysaccharides of Edible Mushrooms, Oyster Mushrooms,” Bulletin of Osaka City University School of Life Sciences, Volume 39 (1991), p. 1-8.

  An object of this invention is to provide the chemical | medical agent and functional food which have an extremely high safety | security and an immunostimulatory effect.

  As a result of searching for mushrooms having an immunostimulatory effect from edible mushrooms produced in Hokkaido, the present inventors have found that the extract of Tamogi mushroom has a high immunostimulatory effect.

  That is, this invention provides the antitumor immunostimulant which uses a bamboo shoot extract as an active ingredient. In another aspect, the present invention provides a tumor cell growth inhibitor comprising a potato extract as an active ingredient. Tumor cells include tumors in the human body such as cervical cancer, leukemia, lymphoma, myeloma, melanoma, pancreatic cancer, prostate cancer, head and neck cancer, breast cancer, lung cancer, colon cancer, stomach cancer, esophageal cancer, ovary Cancer, squamous cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, mesothelioma and epidermoid carcinoma-derived cells, tumor cells transplanted into laboratory animals such as mice, and cells of cell lines derived from human tumors such as HeLa, MeWo, Hs695T, A137, KATO-III, MKN45, MKN28, HuH28, Daudi, Ramos, Raji, U937, HS-Sultan, SKM-1, THP-1, IM-9, MM1S, K562, HL60, HSC-3, HSC-4, TTn, TE-10, IMR-32, U251, PC-3, LNCaP, DU145, DLD-1, WiDr, SW837, Lu135, IMR-90, A549, SK-OV-3, SK-Br- 3, A431, RMG-1, MCF-7, MIAPaCa-2, AsPC1, KP-4. In another aspect, the present invention provides an agent for enhancing the production of immunostimulatory cytokines comprising a potato extract as an active ingredient. Examples of the immunostimulatory cytokine include interleukin (IL) 1, 2, 3, 4, 5, 6, 7, 12, 15, 18, 21, 23, interferon (IFN) α, β, γ, tumor necrosis Factors (TNF) α and β are mentioned. In another aspect, the present invention provides an inhibitor of immunosuppressive T cell increase comprising a potato extract as an active ingredient. In still another aspect, the present invention provides an immune-stimulating health food comprising a rice cake extract and a health food for suppressing tumor cell growth.

FIG. 1 shows suppression of HeLa cell proliferation by a hot water extract of potato.
FIG. 2 shows the inhibition of tumor cell Sarcoma 180 growth by the hot water extract of taro.
FIG. 3 shows an increase in activated antigen expression of human dendritic cells by the extract of hot water from potato.
FIG. 4 shows the enhancement of IL-12 production from human dendritic cells by a hot water extract of cypress salmon.
FIG. 5 shows the results of FACS analysis of inhibitory T cells in mouse spleen cells.
FIG. 6 shows the ratio of GITR positive inhibitory T cells in the spleen of Sarcoma 180 tumor-bearing mice.
FIG. 7 shows the change in tumor volume of Sarcoma 180-transplanted mice that received a scalloped hot water extract and other mushroom extracts.
FIG. 8 shows the mean value of tumor weight of Sarcoma 180 transplanted mice fed with scalloped hot water extract and other mushroom extracts.
FIG. 9 shows the survival rate of Sarcoma 180-transplanted mice fed with a scallop hot water extract and other mushroom extracts.

  Tamamogi is a mushroom belonging to the genus Oyster mushroom and is widely used for food mainly in Hokkaido. The bamboo shoot extract can be produced by the following method. As for the rice cake used in the present invention, a naturally occurring product may be harvested or artificially cultivated in a factory. The bamboo shoots are preferably used within 2 hours after harvest.

  Extract active ingredients from harvested bamboo shoots. The extraction is preferably performed by hot water extraction. For example, the harvested bamboo shoots are put into boiling water of 2-30 times, preferably 5-20 times the weight of the bamboo shoots, and stirred while adding steam. Extract the rice cake extract while stirring for 10 minutes after boiling. The obtained extract may be used as it is, or may be filtered to remove the solid content. Moreover, you may concentrate suitably using a vacuum concentrator, a freeze concentrator, etc. Further, in order to store the extract for a long period of time, after being enclosed in a retort pack, it may be sterilized, for example, at 120 ° C. for 15 minutes, or may be powdered by freeze drying or spray drying.

  The rice cake extract thus obtained suppresses the growth of cell lines derived from human cancer such as HeLa cells and inhibits the growth of sarcomas transplanted into mice, as will be shown in Examples described later. We were able to. Furthermore, it has been shown that the extract of rice moth can enhance the production of immunostimulatory cytokines such as IL-12, activate dendritic cells, and inhibit the appearance of immunosuppressive T cells. These results confirm that the extract of eel paste according to the present invention has immunostimulatory activity and tumor cell growth inhibitory activity.

  The bamboo shoot extract obtained according to the present invention can be used as it is as an immune-stimulated health food or a tumor food growth-preventing health food, but may be added to other foods. The intake is suitably 0.1-10 ml / kg / day, especially 1.8-2.7 ml / kg / day, as an extract with a solid content of 2.5%.

  The immunostimulant according to the present invention is very suitable for addition to health food because it has advantages such as no toxicity and no adverse effects on the living body even when ingested in large amounts.

  The contents of all patents and references explicitly cited herein are hereby incorporated by reference as part of the present specification. In addition, the contents described in the specification and drawings of Japanese Patent Application No. 2004-290528, which is the application on which the priority of the present application is based, are cited herein as a part of this specification.

  EXAMPLES The present invention will be described below in more detail with reference to examples, but the present invention is not limited to these examples.

Preparation of Mushroom Hot Water Extract Hot water extracts of various mushrooms were prepared. Each 1 kg of tamago mushroom, maitake mushroom, shimeji mushroom and shiitake mushroom was placed in 5 kg of boiling water, further heated, and stirred for 10 minutes after boiling. The obtained extract was concentrated under reduced pressure to obtain 240 ml of a 2.5% solid concentrate. The obtained concentrate was subjected to a retort sterilization treatment at 120 ° C. for 15 minutes to obtain a mushroom hot water extract.

HeLa cell growth inhibitory activity The bamboo shoot hot water extract produced in Example 1 was further concentrated under reduced pressure to prepare a 3-fold concentration of bamboo shoot extract, which was used to measure the HeLa cell growth inhibitory activity. . HeLa cells were seeded in a 96-well microplate in MEM medium at 3.7 × 10 ³ cells / well, and the rice cake extract had final solids concentrations of 1.25%, 2.5%, 2.75% and 3 respectively. .75% was added to the wells and cultured at 37 ° C. After 12, 24, and 48 hours, the cell number was factored at 450 nm by the MTT method.

  The results are shown in FIG. At 12 and 24 hours after the addition of the bamboo shoot extract, the number of cells decreased at all concentrations. In 48 hours, a decrease in the number of cells was observed at a concentration of 2.5% or more. That is, it was revealed that the growth of HeLa cells was suppressed by adding the bamboo shoot extract. As a control, the same experiment was performed on normal cells derived from the mouse spleen, but the rice cake extract did not affect the growth of normal cells.

Anti-tumor effect on sarcoma The anti-tumor effect on Sarcoma 180 of the extract of hot water of hot water produced in Example 1 was measured. Sarcoma 180 frozen cells (obtained from Tohoku University Institute for Aging Medicine) are rapidly thawed with warm water at 37 ° C., added with about 10 times the amount of physiological saline, and centrifuged (1000 rpm / min, 5 minutes). The supernatant was removed. After repeating this operation four times, about 3 times the amount of physiological saline was added to the pellet and stirred to obtain a cell solution.

0.1 ml of cell solution (about 5 × 10 ⁶ cells) was transplanted into the abdominal cavity of 5 female mice (Slc: ICR), and sacrificed by cervical dislocation 7 days later. The abdomen was disinfected with ethanol, and ascites was collected using a sterilized syringe. Ascites collected from each animal was mixed, and about 5 × 10 ⁶ cells were transplanted subcutaneously into the groin of a female mouse (Slc: ICR, 5 weeks old, about 18 g).

  Oral administration of the test solution once a day for 10 days before tumor transplantation and 21 days after transplantation in the evaluation experiment (group 1-3) for prevention effect, and 21 days after transplantation for the evaluation experiment (group 4) for treatment effect did. The administration was performed by forcibly administering a predetermined amount of 12 ml / kg of a test solution consisting of hot water extract of hot water and purified water into the stomach of the transplanted animal using a metal sonde for mice. The dosage is as shown in the table below.

Tumor volumes were measured on days 5, 7, 10, 14, 17, 21, and 22 after transplantation. The tumor volume was measured by measuring the short axis (a) and the long axis (b) of the tumor using a caliper, calculated by the following formula, and indicated as mean ± standard deviation.
Tumor volume (cm ³ ) = 4 / 3πa ² b / 2

  The results are shown in FIG. It was shown that the increase in tumor volume was significantly suppressed by administration of the hot water extract of Tamogi. In addition, it was found that a higher effect can be obtained by prophylactic administration of the extract of hot water of Tamogi.

Altered expression of cell surface antigens of dendritic cells The induction of dendritic cells derived from human peripheral blood mononuclear cells is described in Kato et al. (K. Kato, et al., J Leukoc Biol, 70: 941-949, 2001). Prepared according to the procedure. First, 15-20 ml of blood was collected from the left arm vein of a healthy person using a syringe with heparin added, and diluted with an equal volume of PBS under aseptic conditions. The same-diluted blood was layered on 15 ml of Lymphosepar (manufactured by IBL) prepared in advance in a sterile plastic tube, and centrifuged at 1500 rpm for 30 minutes. After centrifugation, the mononuclear cell layer on Lymphosepar was recovered, and the cells were washed twice by centrifugation with PBS. The mononuclear cells were finally diluted in RPMI 1640 medium containing 10% fetal calf serum (manufactured by Sigma), and the cells were added to a 10 cm plastic petri dish and cultured. After 30 minutes at 37 ° C., non-adherent cells (lymphocytes) were removed, and dendritic cell induction medium (RPMI 1640 medium, 10% fetal calf serum, 50 ng / ml human GM- Cultured with CSF (manufactured by Osteogenetics) and 50 ng / ml human IL-4 (manufactured by Osteogenetics) for 7 days at 37 ° C., human mononuclear cell-derived dendritic cells were induced.

The induced dendritic cells were collected in a plastic tube, RPMI1640 medium was added, centrifugal washing was performed, and the number of cells was measured. The cell concentration was finally adjusted to 2 × 10 ⁵ cells / ml with RPMI 1640 medium, 0.5 ml each was added to the 24-well plate, and various mushroom hot water extracts prepared in Example 1 (Tamogi mushroom, maitake, shimeji mushroom, Shiitake) was added at a final concentration of 2% and cultured at 37 ° C for 24 hours.

  Dendritic cells stimulated with mushroom hot water extract are collected in a plastic tube, centrifuged after washing with RPMI1640 medium, and 5 μl each of FITC-labeled anti-human CD45 antibody and PE-labeled anti-human CD86 antibody (both manufactured by eBioscience) are added. After reaction at 4 ° C. for 1 hour, changes in the expression of cell surface antigens were analyzed by FACS (BD). CD54 and CD86 in dendritic cells are molecules essential for eliciting an immune response, and it is known that an increase in antigen expression indicates an activated state of dendritic cells. As a result, as shown in FIG. 3, an increase in the expression of CD86 antigen (shift to the right side of the histogram) was confirmed in dendritic cells to which the hot water extract of paddy rice was added as compared to non-added cells. This enhanced expression was hardly observed in other mushroom extracts (maitake, shimeji). The following table shows changes in the expression of CD54 antigen and CD86 antigen on dendritic cells (analysis with FlowJo software; manufactured by TreeStar).

たもぎ茸熱水抽出液を添加することにより樹状細胞のＣＤ５４、ＣＤ８６抗原の発現が増加していることが確認され、この効果は他のキノコよりも有意に高いものであった。

It was confirmed that the expression of CD54 and CD86 antigens in dendritic cells was increased by adding the hot water extract of Tamogi, and this effect was significantly higher than that of other mushrooms.

IL-12 production from dendritic cells Using the various mushroom hot water extracts produced in Example 1, the effect of enhancing IL-12 production from human dendritic cells was examined. Interleukin 12 (IL-12) is one of cytokines mainly produced from dendritic cells, and is known to be the most important factor for activation of NK cells and Th1 cells. The production enhancing effect of interleukin 12 (IL-12) produced from activated dendritic cells was analyzed by the following method. Dendritic cells induced in the same manner as in Example 4 were finally adjusted to a cell concentration of 2 × 10 ⁵ cells / ml with RPMI 1640 medium, and 0.5 ml each was added to a 24-well plate. For maturation stimulation, CD40 ligand gene introduction by adenovirus (AxCACD40L-F / RGD, 300 particles / cell) was performed, and various mushroom hot water extracts (Tamogi salmon, maitake, shimeji, shiitake) were each at final concentrations. It was added at 2% and cultured at 37 ° C for 48 hours.

  The culture solution of dendritic cells stimulated with mushroom hot water extract for 48 hours was collected in a plastic tube and centrifuged at 10,000 rpm for 5 minutes to collect the supernatant. The culture supernatant was diluted 10 times with PBS, and then the IL-12 content was measured using an ELISA kit (R & D). As a result, dendritic cells to which mushroom hot water extract was not added produced 13.0 ± 0.1 ng / ml, whereas 14.4 ± 0. IL-12 production was enhanced with a significant difference from 1 ng / ml. This effect was higher than that of other mushrooms (Shiitake: 13.8 ± 0.1 ng / ml).

Analysis of inhibitory T cells in spleen cells Experimental animals were tested after 5 weeks old animals purchased from Slc: ICR male SPF mice (Japan SLC Co., Ltd.) were kept in a breeding room for 1 week. Started. The average temperature of the breeding room was 22 ° C. and the humidity was 50%. Sarcoma 180 cells shown in Example 3 were administered subcutaneously to the thigh of an ICR mouse at the number of 5 million cells per mouse using a 1 ml syringe and an injection needle 26G (Terumo).

  On the same day of transplantation, 4 ml / kg of the test substance tofu mushroom extract prepared in Example 1 was forcibly administered into the stomach with a mouse metal sonde until the 21st day of each day. As a control group, an equal amount of physiological saline (Otsuka Pharmaceutical Co., Ltd.) was administered. Seven mice were used per group. The tumor system was measured twice a week after the transplantation, and the tumor volume was measured until 21 days later. As a result, a significant tumor growth inhibitory effect was observed in the group treated with the hot water extract. This result was the same as the growth inhibition shown in Example 3, and the antitumor effect was reconfirmed.

  On day 22 after tumor transplantation, all tumor-transplanted mice were euthanized under deep anesthesia, and the spleen was removed from the abdominal cavity. The isolated spleen was loosened in a petri dish filled with a culture solution to obtain a spleen cell solution mainly composed of lymphocytes. After hemolysis of erythrocytes in the obtained spleen cells, the number of cells was measured and 100,000 cells were put into a plastic tube.

  The larger the tumor line, the larger the spleen was, the fibroblasts were slightly reddish, and many myeloid cell contamination was observed. In mice treated with hot water extract of Tamogi, the spleen was enlarged and the degree of fibroblast was milder than that in mice treated with physiological saline.

Fluorescent staining of inhibitory T cells in splenocytes was performed as shown below. Although it carried out by each administration group 7 animals, the analysis of the inhibitory T cell was enforced using 6 of them. The experiment number of each mouse is as follows.
Group 1: Saline administration group 151, 152, 153, 154, 155, 157
Group 2: Tamogitake hot water extract administration group 251, 252, 254, 255, 256, 257

  FITC-CD4 (RM4-5; 0.5μl / reaction, eBioscience), Biotin-GITR (DTA-1; 0.5μl / reaction, eBioscience), Avidine-PE (0.2μl / reaction, BDpharmingen) Was added and reacted at 4 ° C. for 1 hour. After washing the cells with PBS, dead cells were removed by PI staining, and fluorescence-labeled cells were measured using FACScalibur (BD Bioscience). The number of suppressor T cells was analyzed using FlowJo software (manufactured by Torystar).

  Inhibitory T cells were calculated as a percentage of GITR positive cells in CD4 positive T cells (FITC positive cells). The results are shown in FIGS. GITR-positive inhibitory T cells were significantly decreased in the tumor-bearing mice group (13.2% ± 3.1%) treated with the extract of hot water extract compared to the tumor-bearing mice (33.4% ± 10.6%) administered with saline. Turned out to be.

  From the above results, it was shown that the hot water extract of Tamogi soak contains an active substance that can inhibit the appearance of immunosuppressive T cells induced by the cancer-bearing state. This indicates that the bamboo shoot extract is useful as an immunostimulator.

Comparison of prophylactic anti-tumor effect against sarcoma The prophylactic anti-tumor effect of Sorghum hot water extract and commercial mushroom extract against Sarcoma 180 was measured. As a test substance, the hot water extract of hot water (produced in Example 1) (lots 1 and 2), Agaricus Sengyo-ro Royal and Meshima (registered trademark) Pure PL2.5 were used.

Sarcoma 180 frozen cells (TKG0173, obtained from Tohoku University Institute of Aging Medicine) are rapidly thawed with 37 ° C. warm water, added with about 10 times the amount of physiological saline, and centrifuged (1000 rpm / minute, 5 minutes). And the supernatant was removed. After repeating this operation four times, about 3 times the amount of physiological saline was added to the pellet and stirred to obtain a cell solution. 0.1 ml of cell solution (about 5 × 10 ⁶ cells) was transplanted into the abdominal cavity of the mouse and sacrificed by cervical dislocation 7 days later. The abdomen was disinfected with ethanol, and ascites was collected using a sterilized syringe. Ascites collected from each animal was mixed and about 5 × 10 ⁶ cells were transplanted subcutaneously into the groin area of the test animal.

  As test animals, 6-week-old female mice (Slc: ICR) were used, 10 per group, and food and water were freely fed. The test solution was orally administered once a day for 10 days before tumor transplantation and 35 days after transplantation. Administration is carried out by forcibly administering a predetermined amount of 12 ml / kg test solution consisting of hot water extract or control mushroom extract and purified water into the stomach of transplanted animals using a mouse metal sonde. It was. The dosage is as shown in the table below.

Tumor volume was measured on surviving individuals on the day of experiment, 5, 7, 10, 14, 17, 21, 24, 28, 32 and 36 (end of observation) after transplantation. The tumor volume was calculated by the following formula after measuring the minor axis (a) and major axis (b) of the tumor using calipers.
Tumor volume (cm ³ ) = 4 / 3πa ² b / 2

Tumor weight was measured immediately after discovery for dead cases, and the day after the final administration (35 days after transplantation) for surviving cases. The test animal was euthanized by exsanguination under ether anesthesia, the tumor of the left inguinal region was removed, and its weight was measured. From the average value of the tumor weight of each test group, each tumor growth inhibition rate was calculated by the following formula.
Tumor growth inhibition rate (%) = (1−average tumor weight of administration group / average tumor weight of control group) × 100

The survival rate was calculated by the following formula after examining the survival days of test animals after tumor transplantation.
Survival rate (%) = (average survival days of administration group / average survival days of control group−1) × 100

  A one-way analysis of variance was performed for each parameter (significance level 10%), and if there was a significant difference between groups, Dunnett's multiple comparison test was performed on the mean values (significance levels 5% and 1%).

  The results are shown in FIGS. 7-9. In the Tamogi hot water extract administration group, the mean value of the tumor volume increased daily, but remained at a lower value than that in the control group. The value was significantly lower. The average value of tumor weight was 23.4-29.3% tumor growth suppression compared to the control group, but no statistically significant difference was observed. The life extension rate was 15.5-21.0%. In addition, the survival time was statistically significant compared to the control group.

  In the Agaricus-administered group, the mean value of tumor volume increased daily, but remained at a lower value than the control group, and was statistically significantly lower than the control group intermittently after the fifth day after transplantation. The value is shown. The average value of tumor weight was 5.7% of tumor growth suppression compared to the control group, but no statistically significant difference was observed. The life extension rate was 20.6%. In addition, the survival time was statistically significant compared to the control group. In the Mesima (registered trademark) administration group, the mean value of the tumor volume increased with time, but remained at a lower value than the control group, and statistically compared with the control group intermittently after the fifth day after transplantation. The value was significantly lower. The average value of tumor weight was 24.6% of tumor growth suppression compared to the control group, but no statistically significant difference was observed. The life extension rate was 8.9%. In addition, the survival days did not show a statistically significant difference compared with the control group.

  Based on the above, tumor growth inhibitory effects and life-prolonging effects were recognized by prophylactic administration of the extract of hot water from potatoes.

  The antitumor immunostimulatory agent of the present invention is useful for suppressing the growth of tumor cells.

Claims (10)

An anti-tumor immunostimulant comprising a potato extract as an active ingredient. A tumor cell growth inhibitor comprising tarogi extract as an active ingredient. An agent that enhances the production of immunostimulatory cytokines, comprising a potato extract as an active ingredient. An inhibitor of an increase in immunosuppressive T cells, which comprises an extract of tarogi. An immune-stimulated health food made from bamboo shoot extract. A health food for suppressing tumor cell growth comprising an extract of bamboo shoots. A method of stimulating anti-tumor immunity in a subject by administering the potato extract to the subject. A method for inhibiting the growth of tumor cells in a subject by administering the potato paste extract to the subject. A method of enhancing the production of immunostimulatory cytokines by administering a potato extract to a subject. A method for suppressing an increase in immunosuppressive T cells by administering a potato paste extract to a subject.

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