TW201733599A - Medicines for inflammatory diseases - Google Patents

Abstract

The present invention addresses the problem of providing a treatment for inflammatory disease, in particular, a method and a drug for alleviating the symptoms associated with ulcerative colitis. Cytoimmunotherapy is also used for patients suffering from inflammatory disease.

Description

Medicine for inflammatory diseases

The present invention relates to medicines for inflammatory diseases.

At present, as a cancer cell immune therapy, 1) dendritic cell vaccine therapy, 2) NK cell therapy, 3) γδT cell therapy, 4) αβ T cell therapy, 5) cytotoxic T cell (CTL) therapy, etc. Document 1 and Non-Patent Document 1).

The so-called dendritic cell vaccine therapy phagocytizes the dendritic cells (Dendritic Cells: DC) differentiated from the single blood in the peripheral blood into the target cancer cells and sends them back to the body to serve as cancer or pathogens. The label (antigen) functions as a cell (mainly a T cell) that has the ability to damage cancer cells or an "antigen presenting cell (APC)" that has the role of an antibody-producing B cell. This is a method of treating cancer.

The so-called NK (Natural Killer) cell therapy uses a complex stimulating substance such as IL-2 to activate, proliferate, and return the cells having high ability to damage abnormal cells such as NK cells contained in the peripheral blood. Inside, and the method of treating cancer. NK cells are one type of lymphocytes that bear the natural immune system. They have strong cytotoxicity, specifically, mechanisms for recognizing and killing cells whose MHC class I molecules are reduced or disappeared, and as antibody-dependent cells. A major effector cell in injury (ADCC) functions as a function, and thus is an important cell for rejecting tumor cells or virus-infected cells.

γδT cells are central cells responsible for the biological defense response known as lymphoid stress-surveillance. The so-called γδT cell therapy is a small amount of blood in the peripheral blood obtained from the patient. There are (1 to 5%) γδ T cells holding the γδ-type T cell receptor (Vγ9Vδ2 receptor) which selectively proliferate and are returned to the body for treatment. The γδT cells can obtain an "antigen non-specific" antitumor effect of killing cancer by recognizing molecules that are commonly expressed on the surface of cancer cells without depending on the "antigen" recognized by the αβ T cells.

The so-called αβ T cell therapy is a method in which the lymphocytes contained in the peripheral blood are cultured for about 2 weeks using interleukin-2 (IL-2) and an anti-CD3 antibody, and the whole is activated/proliferated and returned to the body for treatment. law. The T lymphocytes of the peripheral blood are mostly αβT cells holding the αβ type T cell receptor (T Cell Receptor: TCR), that is, the proliferating cells are mostly αβ T cells. The αβ T cell line presents an antigen by the above dendritic cells or the like, and attacks the cells holding the antigen.

Cytotoxic T cell (CTL) therapy induces cells by stimulating T cells in peripheral blood mononuclear cells using cancer cells in vitro Injury T cells (CTL) are returned to the body for treatment. Cancer cells themselves act as antigen-presenting cells (APCs) and can efficiently increase cytotoxic T cells (CTLs) that possess the ability to attack cancers of their own.

Compared with the previous three treatments of surgical treatment, radiation therapy, and chemotherapy, immune cell therapy has almost no side effects, and has been applied as an advanced medical treatment to actual lung cancer patients as a fourth cancer treatment method.

[Previous Technical Literature] [Patent Document]

[Patent Document 1] International Publication No. 2006/006720

[Non-Patent Document 1] MEDINET Website

Http://www.medinet-inc.co.jp/english/service/technology.html

The physician or the like as the inventor of the present invention is a clinician or the like who actually applies the cancer immunocytotherapy to the patient. When the inventors of the present invention performed the observation of the symptoms of the patient who performed the cancer immunotherapy, it was found that the symptoms of the patient with the onset of ulcerative colitis were alleviated.

That is, the object of the present invention is another use of immune cell therapy, From large indications to inflammatory diseases, in particular, ulcerative colitis.

The term "inflammatory disease" refers to a disease accompanied by an excessive production of inflammatory interleukins. Examples of inflammatory interleukins include IL-1, IL-6, IL-8, IL-12, IL-18, and tumor necrosis factor (TNFα/β).

Therefore, the so-called inflammatory disease is not limited thereto, but Crohn's disease, rheumatoid arthritis, and dryness (including cognac vulgaris, joint dryness, pustular dryness, dry red skin) Symptoms, ankylosing spondylitis, ulcerative colitis, and refractory omental uveitis caused by Behcet's disease are consistent with this.

The so-called inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis, which is characterized by recurrence and remission of chronic inflammation of the digestive tract that causes diarrhea and abdominal pain.

Inflammation is caused by a cellular immune response in the mucosa of the digestive tract. Although the cause is unknown, in the immune response, the release of inflammatory mediators such as interleukins, interleukins, tumor necrosis factor (TNF), and lipid mediators is involved.

<ulcerative colitis>

The so-called ulcerative colitis (UC: Ulcerative colitis) An inflammatory disease of the large intestine that is eroded or ulcerated in the mucosa of the large intestine. As a characteristic symptom, it is accompanied by or not accompanied by sputum and abdominal pain under the blood. The lesion has the property of extending continuously and ascending from the rectum, maximally extending from the rectum to the colon as a whole. Ulcerative colitis is classified as follows by expansion or passage of lesions.

1) Classification through the expansion of lesions: colitis, left colitis, proctitis

2) Classification of the disease period: active period, remission period

3) Classification by severity: mild, moderate, severe, inflammatory

4) Classification by clinical course: reburning remission type, chronic persistent type, acute irritability type, primary attack type

The number of patients with ulcerative colitis in Japan is about 160,000, and it will occur from young to old, and there is no difference in gender. Regarding the cause of ulcerative colitis, it is generally considered that the abnormality of autoimmune response or eating life is the cause, but it is still unknown.

If ulcerative colitis occurs, it can be seen that sputum or bloody stools are sometimes accompanied by spastic or persistent abdominal pain. If it develops into a serious illness, systemic symptoms such as fever, weight loss, and anemia may occur. In addition, symptoms of the skin, joints or eye symptoms may sometimes occur as complications other than the intestinal tract.

For ulcerative colitis, oral/retinal administration, adrenal corticosteroids, blood cell component removal therapy, immunomodulatory/inhibitory drugs, by pharmaceuticals such as 5-aminosalicylic acid (5-ASA), Internal treatments such as anti-TNFα receptor antagonists and anti-TNFα antibodies inhibit intestinal inflammation The symptoms are improved, but the method that leads to complete cure does not exist. In the case of medical treatment, the symptoms have not improved, and sometimes surgical treatment such as total enema is performed.

Since it is generally considered to be caused by a cellular immune response, in addition to the above-described drug therapy/surgical therapy, blood cell component removal therapy (CAP therapy) or the like is also used as a treatment for non-drug therapy. For example, for patients with severe septic disease and refractory patients, GCAP therapy for removing granules and single balls is also applied. For steroid-resistant patients, white blood cells (granule ball, single ball and lymphocyte) removal therapy (LCAP) is also applied. Therapy, etc., although it has achieved certain results, has not yet established a universally effective treatment, but has been designated as a specific medical disease in the Ministry of Health, Labor and Welfare of Japan.

The inventors of the present invention verified the biochemical parameters in addition to the time-lapse observation of the patient who performed the above-described immunocytotherapy, and confirmed that the immune cells proliferating in vitro were returned to the opposite to the above-described blood cell component removal therapy. The patient's immune cell therapy did achieve the alleviation of the symptoms of inflammatory bowel disease, and completed the invention.

Thus, with respect to the present invention, the constitution of the present invention is as follows [1] to [29].

[1] A pharmaceutical composition for treating or preventing an inflammatory disease, which comprises an immune cell;

[2] The pharmaceutical composition according to [1], wherein the immune cell is a lymphocyte;

[3] The pharmaceutical composition according to [1], wherein the immune cell is a cultured lymphocyte;

[4] The pharmaceutical composition according to [3], wherein the lymphocyte system is composed of any one of αβT cells, γδT cells, NK cells, or CD16 ⁺ and/or CD56 ⁺ cells;

[5] The pharmaceutical composition according to [1], wherein the immune cell line is derived from a peripheral blood mononuclear sphere;

[6] The pharmaceutical composition according to any one of [1] to [5] wherein the inflammatory disease is an inflammatory bowel disease;

[7] The pharmaceutical composition according to [6], wherein the inflammatory bowel disease is ulcerative colitis;

[8] The pharmaceutical composition according to any one of [1] to [7] which is administered in combination with the administration of a TNFα inhibitor.

[9] The pharmaceutical composition according to [8], wherein the TNFα inhibitor is an anti-TNFα antibody.

[10] Use of an isolated immune cell for the manufacture of a medicament for the treatment or prevention of an inflammatory disease;

[11] The use of [10], wherein the immune cells are isolated lymphocytes;

[12] The use of [11], wherein the immune cell is a lymphocyte that has been cultured after being isolated;

[13] The use of [12], wherein the lymphocyte system has as a main component of any one of αβT cells, γδT cells, NK cells, or CD16 ⁺ and/or CD56 ⁺ cells;

[14] The use of [10], wherein the immune cell line is derived from a peripheral blood mononuclear sphere;

[15] The use of any one of [10] to [14], wherein the inflammatory disease For inflammatory bowel disease;

[16] The use of [15], wherein the inflammatory bowel disease is ulcerative colitis.

[17] A method of treating or preventing an inflammatory disease, comprising administering an isolated immune cell to a patient;

[18] The method of [17], wherein the immune cell is a lymphocyte;

[19] The method according to [17], wherein the immune cell is a cultured lymphocyte;

[20] The method according to [19], wherein the lymphocyte system has as a main component of any one of αβT cells, γδT cells, NK cells, or CD16 ⁺ and/or CD56 ⁺ cells;

[21] The method of [17], wherein the immune cell line is derived from a peripheral blood mononuclear sphere;

[22] The method according to any one of [17], wherein the inflammatory disease is an inflammatory bowel disease;

[23] The method according to [22], wherein the inflammatory bowel disease is ulcerative colitis.

[24] A method for treating or preventing an inflammatory disease, comprising the steps of: 1) a step of removing a peripheral blood mononuclear ball from a patient, 2) a step of culturing a peripheral blood mononuclear ball to obtain an immune cell, and 3 a step of administering the obtained immune cells to a patient;

[25] The method of [24], wherein the immune cell is a lymphocyte;

[26] The method according to [25], wherein the lymphocyte system has as a main component of any one of αβT cells, γδT cells, NK cells, or CD16 ⁺ and/or CD56 ⁺ cells;

[27] The method according to any one of [24], wherein the inflammatory disease is an inflammatory bowel disease;

[28] The method according to [27], wherein the inflammatory bowel disease is ulcerative colitis.

[29] A method for producing a therapeutic or prophylactic agent for an inflammatory bowel disease, comprising culturing a peripheral blood mononuclear ball to obtain a composition, and the therapeutic or prophylactic agent is the composition As an active ingredient.

By using the present invention, it is possible to perform treatment and inflammation reduction of inflammatory diseases with high QOL (Quality of Life) of patients.

Hereinafter, embodiments for carrying out the invention will be described.

<Preparation of immune cell modulation>

First, peripheral blood mononuclear cells (PBMCs) which are the source of cells of immune cells are prepared. The so-called PBMCs here mean the blood from the peripheral blood. A cell group containing lymphocytes (NK cells, NKT cells, αβT cells, γδT cells, etc.), single spheres, and the like is isolated. The method of preparing the PBMCs is not particularly limited. For example, PBMCs can be obtained by separating the peripheral blood obtained by blood collection by density gradient centrifugation. The amount of blood to be collected at a time may be appropriately set in accordance with the type of immune cell therapy and the patient to be treated, for example, about 20 to 75 mL.

Further, in the case where it is necessary to secure a large number of cells, PBMCs can be directly obtained by using a single-core ball component using a component blood collection device.

The PBMCs taken are suspended in a culture medium (medium), and intercellular substances are added and cultured in accordance with the type of immune cells to be proliferated or activated. The so-called culture includes a step carried out for the purpose of proliferation, activation or processing of cells such as lymphocytes.

The type of the culture solution in which the PBMCs are suspended is not particularly limited as long as it can proliferate the immune cells. Examples of such a culture solution include AIM-V medium, RPMI-1640 medium, Dulbecco modified Eagle medium (DMEM), and Iscove medium. Serum may also be added to these cultures as needed. As an example of the serum to be added, autologous plasma can be mentioned.

The culture conditions of the PBMCs are not particularly limited as long as they can proliferate and activate the immune cells. Usually, it can be cultured for 7 to 20 days at 34 to 38 ° C (preferably 37 ° C) and 2 to 10% (preferably 5%) CO ₂ . At this time, it is appropriate to add a culture solution in accordance with the number of cells to be cultured. Further, in combination with an increase in the amount of the culture solution, it is preferable to add IL-2 or the like.

<Method of manufacturing NK cells>

In the case of producing NK cells, an agonist of a molecule which specifically expresses an anti-CD16 antibody or the like, or IL-2 or the like is added to a medium and cultured (for example, Japanese Patent No. 4275680). As the NK cells used in the medicine of the present invention, any method can be used. Further, it is also possible to use CD16 ⁺ and/or CD56 ⁺ cells prepared by the method described in the patent document WO 2009/151183 or the like as NK cells.

<Method for producing γδT cells>

Next, an example of a method for producing γδT cells will be exemplified.

The PBMCs taken were inoculated to a culture solution supplemented with bisphosphonate and IL-2, and γδT cells were cultured. By culturing PBMCs in the presence of bisphosphonate and IL-2, γδT cells can be selectively proliferated and activated to prepare a cell group containing high-purity γδT cells (see Patent Document 1).

In the present invention, the so-called bisphosphonate is not particularly limited and refers to a compound having a skeleton of P-C-P. The bisphosphonate to be used in the present invention is, for example, a compound represented by the following general formula [Chemical Formula 1], a salt thereof, and the like.

In the above [Chemical Formula 1], R is a hydrogen atom or a lower alkyl group, and R ₁ and R ₂ are each independently selected from a hydrogen atom, a halogen atom, a hydroxyl group, an amine group, a thiol group, a substituted aryl group, or the like. A group consisting of a substituted alkyl group, a lower alkylamino group, an aralkyl group, a cycloalkyl group, and a heterocyclic group, and R ₁ and R ₂ may form part of the same cyclic structure.

The substituents in the above R ₁ and R ₂ are selected, for example, from a halogen atom, a lower alkyl group, a hydroxyl group, a thiol group, an amine group, an alkoxy group, an aryl group, an arylthio group, an aryloxy group or an alkylthio group. a group consisting of a cycloalkyl group, a heterocyclic group, and the like.

In the present specification, as the halogen atom, for example, a fluorine atom, a chlorine atom, a bromine atom or the like is shown, and as the alkyl group, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group or a butyl group is shown. a straight or branched chain C ₁ -C ₃₀ alkyl group, etc.; a pentyl group, a heptyl group, an octyl group, a fienyl group, etc.; as a lower alkyl group, for example, a linear or branched chain C ₁ -C ₁₀ alkane is shown. Examples of the aryl group include, for example, a phenyl group, a naphthyl group, and the like; as the aralkyl group, for example, an aryl-lower alkyl group; and the cycloalkyl group, for example, a cyclooctyl group or an adamantane group; The group is a C ₁ -C ₁₀ cycloalkyl group or the like; and the heterocyclic group is a pyridyl group, a furyl group, a pyrrolidinyl group, an imidazolyl group, a quinolyl group or an isoquinolyl group.

Further, in the present invention, the bisphosphonate is preferably pharmaceutically The permissible form is a bone resorption inhibiting action, and is generally used as a therapeutic drug for osteoporosis. As an example, it includes pamidronic acid, alendronic acid, zoledronic acid, risedronic acid, ibandronic acid, Incadronic acid and the salts thereof, and the hydrates thereof. These are amine bisphosphonates having a nitrogen atom, particularly preferably pamidronic acid, alendronate, zoledronic acid, and the like, and the hydrates thereof. As a commercially available bisphosphonate bone metabolism improving agent, for example, pamidronate disodium pentahydrate (AREDIA (registered trademark); Novartis Pharma Co., Ltd.), zoledronic acid hydrate (ZOMETA (registered) Trademark); Novartis Pharma Co., Ltd.), etc.

The concentration of the bisphosphonate added during the culture of the PBMCs is preferably in the range of 0.05 to 100 μM, more preferably in the range of 0.1 to 30 μM. More specifically, in the case where pamidronic acid or a salt thereof or the hydrate, alendronic acid or a salt thereof or the hydrate thereof is added as a bisphosphonate, the concentration of the bisphosphonate is preferably It is in the range of 1~30μM. Further, in the case where zoledronic acid or a salt thereof or the hydrate thereof is added as the bisphosphonate, the concentration of the bisphosphonate is preferably in the range of 0.1 to 10 μM.

The concentration of IL-2 added during the culture of PBMCs is preferably in the range of 50 to 2000 U/mL, more preferably in the range of 400 to 1000 U/mL.

The culture conditions of the PBMCs are not particularly limited as long as the γδT cells can be proliferated and activated. Usually, it can be cultured for 7 to 14 days in the presence of 34 to 38 ° C (preferably 37 ° C) and 2 to 10% (preferably 5%) CO ₂ . At this time, it is appropriate to add a culture solution in accordance with the number of cells to be cultured. Further, in combination with the increase in the amount of the culture solution, IL-2 is suitably added so as to be 50 to 2000 U/mL, more preferably 400 to 1000 U/mL.

By the above sequence, a large number of cell groups including γδT cells can be obtained. The obtained cell group can be used as a cell to be administered to a patient in γδT cell therapy as will be described later.

The culture system is carried out at 34 to 38 ° C, preferably 37 ° C, and 2 to 10%, preferably 5% of CO ₂ , and the culture period is preferably from 1 to 20 days, particularly preferably from 1 to 2 weeks. about.

The medium to be used is not particularly limited, and AIM-V medium (Invitrogen), RPMI-1640 medium (Invitrogen), Dulbecco modified Eagle medium (Invitrogen), Iscove medium (Invitrogen), KBM medium (Kohjin Bio), ALyS medium can be used. A commercially available medium used for cell culture such as (Cell Science Research Institute). In addition, 5 to 20% of bovine serum, bovine fetal serum, human serum, human plasma, and the like may be added as needed.

<Method for producing αβ T cells>

Next, an example of a method for producing αβ T cells will be described.

As a method of culturing αβ T cells, a method using an anti-CD3 antibody and IL-2 is preferred.

The anti-CD3 antibody may be added to the culture medium or may be solid-phased in the culture vessel, and it is known to inoculate the lymphocytes with the anti-CD3 antibody by immobilizing the lymphocytes. A culture vessel such as a flask can be cultured more suitably (for example, Japanese Patent No. 3056230). The concentration of IL-2 is preferably added so as to be in a concentration of 100 to 2000 IU/mL in the medium.

The culture system is carried out at 34 to 38 ° C, preferably 37 ° C, and 2 to 10%, preferably 5% of CO ₂ , and the culture period is preferably from 1 to 20 days, particularly preferably from 1 to 2 weeks. about.

The medium to be used is not particularly limited, and AIM-V medium (Invitrogen), RPMI-1640 medium (Invitrogen), Dulbecco modified Eagle medium (Invitrogen), Iscove medium (Invitrogen), KBM medium (Kohjin Bio), ALyS medium can be used. A commercially available medium used for cell culture such as (Cell Science Research Institute). In addition, 5 to 20% of bovine serum, bovine fetal serum, human serum, human plasma, and the like may be added as needed.

<medicine containing immune cells>

The medicine of the present invention is a medicine for treating/preventing an inflammatory disease, which comprises the immune cells produced by the above-described production method of the present invention.

The pharmaceutical system of the present invention is, for example, an injection (cell suspension) obtained by suspending immune cells produced by the production method of the present invention in a liquid (for example, physiological saline) which can be used as a pharmaceutical. The injection can be injected intravenously or intradermally, subcutaneously, etc., or directly into the lesion, or can be administered as a drip systemic administration.

The medicine of the present invention contains immune cells as an essential component, and may contain other components as an optional component.

The number of immune cells contained in the medicine of the present invention can be appropriately set depending on the administration method or the type of the disease. Usually, it is set so as to be 10 ⁸ to 10 ¹² /person (preferably 10 ⁹ /person).

The method for producing the medicine of the present invention is not particularly limited. For example, the medicine of the present invention can be recovered by centrifugation or the like by 1) the cultured immune cells; 2) the recovered immune cells are washed with a washing solution (for example, physiological saline or PBS). Washing; 3) recovering the washed immune cells by centrifugation or the like; 4) suspending the recovered immune cells in a liquid (for example, physiological saline) that can be used as a pharmaceutical, and manufacturing as A drip that is administered intravenously.

Hereinafter, the present invention will be described in detail with reference to the embodiments, but the present invention is not limited by these examples.

[Example 1] <1. Culture and administration of immune cells>

The patient who had obtained the consent had 67.5 mL of peripheral blood, and the peripheral blood mononuclear sphere was cultured by centrifugation. In the Putin Clinic Yokohama CPC (Cell Processing Facility), approximately 14 days of culture was carried out to prepare and activate autologous NK cells. After the quality inspection, the obtained activated autologous NK cells were prepared as a drip, and the patient was administered intravenously.

<2. Results>

The patient developed bloody stools and frequent symptoms from ulcerative colitis several years ago, and no improvement was observed even with mesalazine (5-aminosalicylic acid: 5-ASA). Therefore, since the administration of infliximab was started 2 years ago, it was extended from the interval of 2 weeks to the interval of 4 weeks according to the general usage/dosage, and it was performed at intervals of 6 to 8 weeks. Cast. With the administration of infliximab (anti-human TNFα monoclonal antibody), although the symptoms were alleviated, the symptoms of bloody stools continued.

After the first dose of NK cells in March 2015, the blood will be relieved from the next day, and soon the blood will disappear. Therefore, it was discussed with the attending physician of ulcerative colitis that the administration of infliximab was discontinued and it became observed. A total of five doses have been administered so far, and the patient has no symptoms of bloody stools or other ulcerative colitis, and continues to be mild (as of the end of January 2017). In addition, a significant improvement in the inflammatory state was also confirmed by the results of the endoscopic examination performed after the third administration.

(to sum up)

Even if the long-term administration of the therapeutic drug for ulcerative colitis is not improved, the administration of the immune cells is continued in a state of slowing down without administration of the therapeutic drug, and thus, under the comprehensive diagnosis of the clinician It is confirmed that the immunocyte treatment is effective for the inflammatory disease, especially the healing of the symptoms of ulcerative colitis.

Therefore, the immunotherapy according to the present invention can be used as a substitute for a medicine for remedy the symptoms caused by the formation of an inflammatory interleukin, such as mesalazine or infliximab. Use it below.

As a therapeutic target, it is not only ulcerative colitis, but also a disease associated with inflammatory interleukins, especially TNFα, such as Crohn's disease, rheumatoid arthritis, and dryness (including cognac vulgaris, joint disease). Sexual dryness, pustular dryness, dry erythroderma), ankylosing spondylitis, refractory omental uveitis caused by Bezi's disease.

[Industrial Applicability]

The therapeutic agent of the present invention can be used for the treatment of inflammatory diseases, particularly the symptoms of ulcerative colitis, by a medical technique that has not been completely cured in the past.

Claims (29)

A pharmaceutical composition for treating or preventing an inflammatory disease, which comprises an immune cell. The pharmaceutical composition according to claim 1, wherein the aforementioned immune cells are lymphocytes. The pharmaceutical composition according to claim 1, wherein the aforementioned immune cells are cultured lymphocytes. The pharmaceutical composition according to claim 3, wherein the lymphocyte system comprises, as a main component, any one of αβT cells, γδT cells, NK cells, or CD16 ⁺ and/or CD56 ⁺ cells. The pharmaceutical composition of claim 1, wherein the aforementioned immune cell line is derived from a peripheral blood mononuclear ball. The pharmaceutical composition according to any one of claims 1 to 5, wherein the inflammatory disease is an inflammatory bowel disease. The pharmaceutical composition according to claim 6, wherein the inflammatory bowel disease is ulcerative colitis. The pharmaceutical composition according to any one of claims 1 to 7, which is administered in combination with the administration of the TNFα inhibitor. The pharmaceutical composition according to claim 8, wherein the TNFα inhibitor is an anti-TNFα antibody. The use of an isolated immune cell for the manufacture of a medicament for the treatment or prevention of an inflammatory disease. The use of claim 10, wherein the aforementioned immune cells are isolated lymphocytes. The use of claim 11, wherein the lymphocytes are cultured lymphocytes after isolation. The use of claim 12, wherein the lymphocyte system comprises as the main component any one of αβT cells, γδT cells, NK cells, or CD16 ⁺ and/or CD56 ⁺ cells. The use of claim 10, wherein the aforementioned immune cell line is derived from a peripheral blood mononuclear sphere. The use according to any one of claims 10 to 14, wherein the aforementioned inflammatory disease is an inflammatory bowel disease. The use of claim 15, wherein the aforementioned inflammatory bowel disease is ulcerative colitis. A method of treating or preventing an inflammatory disease comprising administering an isolated immune cell to a patient. The method of claim 17, wherein the aforementioned immune cells are lymphocytes. The method of claim 18, wherein the lymphocytes are cultured lymphocytes. The method of claim 19, wherein the lymphocyte system comprises as the main component any one of αβT cells, γδT cells, NK cells, or CD16 ⁺ and/or CD56 ⁺ cells. The method of claim 17, wherein the aforementioned immune cell line is derived from a peripheral blood mononuclear sphere. The method of any one of claims 17 to 21, wherein the aforementioned inflammatory disease is an inflammatory bowel disease. The method of claim 22, wherein the aforementioned inflammatory bowel disease is ulcerative colitis. A method for treating or preventing an inflammatory disease, comprising the steps of: 1) a step of removing a peripheral blood mononuclear ball from a patient, 2) a step of culturing a peripheral blood mononuclear ball to obtain an immune cell, and 3) The step of administering the obtained immune cells to the patient. The method of claim 24, wherein the aforementioned immune cells are lymphocytes. The method of claim 25, wherein the lymphocyte system comprises as the main component any one of αβT cells, γδT cells, NK cells, or CD16 ⁺ and/or CD56 ⁺ cells. The method of any one of claims 24 to 26, wherein the aforementioned inflammatory disease is an inflammatory bowel disease. The method of claim 27, wherein the aforementioned inflammatory bowel disease is ulcerative colitis. A method for producing a therapeutic or prophylactic agent for an inflammatory bowel disease, which comprises culturing a peripheral blood mononuclear ball to obtain a composition, and the therapeutic or prophylactic agent uses the composition as an active ingredient.