COMPOSITION FOR ANTICANCER TREATMENT, COMPRISING NK CELLS AND FUSION PROTEIN COMPRISING IL-2 PROTEIN AND CD80 PROTEIN

Abstract

An anticancer agent is provided comprising, as active ingredients, NK cells and a fusion protein comprising an IL-2 protein and a CD80 protein. In one specific formulation, a fusion protein comprising a CD80 fragment, an immunoglobulin Fc region, and an IL-2 variant can activate immune cells such as natural killer cells. Furthermore, since the pharmaceutical composition can effectively inhibit cancer, when co-administered with natural killer cells, it increases immune activity in the body, making it effective for cancer treatment and thus highly applicable to industry.

Description

COMPOSITION FOR ANTICANCER TREATMENT, COMPRISING NK CELLS AND FUSION PROTEIN COMPRISING IL-2 PROTEIN AND CD80 PROTEIN TECHNICAL FIELD The present invention relates to a pharmaceutical composition for the treatment of cancer that includes, as active ingredients, a fusion protein comprising a CD80 protein and a 1L-2 variant, and an NK cell. BACKGROUND OF THE TECHNIQUE IL-2, also called T-cell growth factor (TCGF), is a globular glycoprotein that plays a central role in lymphocyte production, survival, and homeostasis. The IL-2 protein is 15.5 kDa to 0 kDa in size and consists of 133 amino acids. IL-2 is involved in various immune actions by binding to the IL-2 receptor, which has three distinct subunits. Additionally, IL-2 is primarily synthesized by activated T lymphocytes, particularly CD4+ helper T cells. IL-2 stimulates T-cell proliferation and differentiation, induces the production of cytotoxic T lymphocytes (CTLs), and promotes the differentiation of peripheral blood lymphocytes into cytotoxic T lymphocytes and lymphokine-activated killer (LAK) cells. Meanwhile, CD80, also known as B7-1, is a member of the B7 family of membrane-bound proteins involved in immune regulation by binding to its ligand and thus providing both costimulatory and co-inhibitory responses. CD80 is a transmembrane protein expressed on the surface of T lymphocytes, B lymphocytes, dendritic cells, and monocytes. CD80 is known to bind to CD28, CTLA4 (CD152), and PD-L1. CD80, CD86, CTLA4, and CD28 are involved in a costimulatory-co-inhibitory system. For example, they regulate T lymphocyte activity and are involved in T lymphocyte proliferation, differentiation, and survival. Additionally, natural killer cells (NK cells) are known to exhibit anticancer activity by eliminating cancer cells (Loris Zamai et al., J. Immunol., 178:4011-4016, 2007). NK cell activity is regulated by a balance of several activating and inhibitory signaling receptors. The anticancer activity of NK cells is also known to be achieved by discriminating cancer cells through various receptors. CAzann / zznz / E / YiAi immune cells are present on the surface. Due to the major histocompatibility complex (MHC) class I present on normal cells, normal cells are recognized by inhibitory receptors on NK cells and are therefore not attacked. However, cancer cells or some infected cells are eliminated by NK cells due to the reduction of MHC class I or ligands that activate NK cell receptors. NK cells can also eliminate cancer stem cells from cancer cells and are therefore a focus of attention as a source of therapies that can not only inhibit cancer development, proliferation, and metastasis, but also reduce cancer recurrence after complete recovery. DETAILED DESCRIPTION OF THE INVENTION TECHNICAL PROBLEM Accordingly, as a result of the study to develop a safe and effective IL-2, the present inventors discovered that the co-administration of a novel fusion protein dimer comprising an IL-2 protein and a CD80 protein in one molecule in combination with natural killer cells exhibits an excellent anticancer effect and has completed the present invention. SOLUTION TO THE PROBLEM To achieve the above purpose, according to one aspect of the present invention, an anticancer agent is provided which includes, as active ingredients, a fusion protein dimer comprising an IL-2 protein and a CD80 protein, and a natural killer cell. EFFECTS OF THE INVENTION It was confirmed that a fusion protein dimer comprising an IL-2 protein and a CD80 protein can not only activate immune cells but also exhibit synergistic effects when administered in combination with natural killer cells. Therefore, such a combination therapy may be usefully applied to cancer treatment. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic diagram of one modality of a fusion protein dimer used in the present invention; CAzann / zznz / E / YiAi Figure 2 shows an SDS-PAGE image that confirms the fusion protein dimer that was obtained (GI-101); Figure 3 shows the size exclusion chromatography (SEC) analysis of the fusion protein dimer obtained (GI-101); Figure 4 shows an SDS-PAGE image that confirms the Fc-IL2v2 fusion protein that was obtained; Figure 5 shows the size exclusion chromatography (SEC) analysis of the Fc-IL2v2 fusion protein that was obtained; Figure 6 shows an SDS-PAGE image that confirms the hCD80-Fc fusion protein that was obtained; Figure 7 shows the size exclusion chromatography (SEC) analysis of the hCD80-Fc fusion protein that was obtained; Figure 8 shows the viability results of cancer cells following treatment with GI-101 or CD80-Fc+Fc-IL2v2 when a K562 cell line is cultured alone without natural killer cells (E / T ratio = 0 / 1). In this case, E indicates an NK cell as the effector cell and T indicates a K562 cancer cell line as the target cell. Figure 9 shows the viability results of cancer cells following treatment with GI-101 or CD80-Fc+Fc-IL2v2 when cultured as an MDA-MB-231 cell line alone without natural killer cells (E / T ratio = 0 / 1). In this case, E indicates an NK cell as the effector cell and T indicates an MDA-MB-231 cancer cell line as the target cell. Figure 10 shows the viability results of cancer cells following treatment with GI-101 or CD80-Fc+Fc-IL2v2 when an HCT-116 cell line is cultured alone without natural killer cells (E / T ratio = 0 / 1). In this case, E indicates an NK cell as the effector cell and T indicates an HCT-116 cancer cell line as the target cell. Figure 11 shows the viability results of cancer cells following treatment with GI-101 or CD80-Fc+Fc-IL2v2 when cultured as an A549 cell line alone without natural killer cells (E / T ratio = 0 / 1). In this case, E indicates an NK cell as the effector cell and T indicates an A549 cancer cell line as the target cell. Figure 12 shows the results of cancer cell viability according to treatment with the combined GL101 or CD80-Fc+Fc-IL2v2 material when a K562 cell line (target cell) is co-cultured with natural killer cells (effector cells) in an E / T ratio of 1 / 3. Here, the Y-axis = 0 indicates that the viability signal interval (red signal) of cancer cells at the time of initial seeding is set to 0. The Y-axis > 0 represents the case where the viability signal interval of cancer cells discovered after seeding increases, indicating that the cell proliferation rate is faster than the cell death rate (cell proliferation rate > cell death rate). That is, it can be seen as an increase in the number of cancer cells. However, it is believed that the smaller the value of the increase, the more cancer cell proliferation is inhibited.Meanwhile, if the area of ​​the measured viable cancer cells is less than that of the viable cancer cells determined at the time of initial seeding, it is expressed as a negative value, indicating that the cell proliferation rate is slower than the cell death rate (cell proliferation rate). <tasa de muerte celular). Es decir, la disminución en el área en comparación con la medida en el momento de la siembra inicial se expresa como un valor negativo. Por lo tanto, se sugiere que un valor negativo mayor puede estar en relación no solo con la inhibición de la proliferación de células cancerosas sino también con la muerte de las células cancerosas de esta. Figure 13 shows the results of cancer cell viability according to treatment with a combined GI-101 or CD80-Fc+Fc-IL2v2 material when a K562 cell line is co-cultured with natural killer cells in an E / T = 1 / 1 ratio. Figure 14 shows the results of cancer cell viability according to treatment with a combined GL101 or CD80-Fc+Fc-IL2v2 material when a K562 cell line is co-cultured with natural killer cells in an E / T ratio = 3 / 1. Figure 15 shows the results of cancer cell viability according to treatment with a combined GI-101 or CD80-Fc+Fc-IL2v2 material when a K562 cell line is co-cultured with natural killer cells in an E / T ratio = 10 / 1. Figure 16 shows the results of cancer cell viability according to treatment with a combined GL101 or CD80-Fc+Fc-IL2v2 material when co-cultured an MDA-MB231 cell line (target cell) with natural killer cells (effector cells) in an E / T ratio of 1 / 3. Figure 17 shows the results of cancer cell viability according to treatment with a combined GI-101 or CD80-Fc+Fc-IL2v2 material when co-cultured an MDA-MB231 cell line with natural killer cells in an E / T ratio = 1 / 1. Figure 18 shows the results of cancer cell viability according to treatment with combined GI-101 or CD80-Fc+Fc-IL2v2 material when an MDA-MB231 cell line is co-cultured with natural killer cells in an E / T ratio = 3 / 1. Figure 19 shows the results of cancer cell viability according to treatment with combined GI-101 or CD80-Fc+Fc-IL2v2 material when co-cultured with an MDA-MB231 cell line with natural killer cells in an E / T ratio = 10 / 1. Figure 20 shows the results of cancer cell viability according to treatment with combined GI-101 or CD80-Fc+Fc-lL2v2 material when co-cultured with an HCT-116 cell line (target cell) with natural killer cells (elector cells) in an E / T ratio of 1 / 3. Figure 21 shows the results of cancer cell viability according to treatment with combined GI-101 or CD80-Fc+Fc-IL2v2 material when an HCT-116 cell line is co-cultured with natural killer cells in an E / T ratio = 1 / 1. Figure 22 shows the results of cancer cell viability according to treatment with combined GI-101 or CD80-Fc+Fc-IL2v2 material when co-cultured with an HCT-116 cell line with natural killer cells in an E / T ratio = 3 / 1. Figure 23 shows the results of cancer cell viability according to treatment with combined GI-101 or CD80-Fc+Fc-IL2v2 material when an HCT-116 cell line is co-cultured with natural killer cells in an E / T ratio = 10 / 1. Figure 24 shows the results of cancer cell viability according to treatment with combined GI-101 or CD80-Fc+Fc-IL2v2 material when an A549 cell line (target cell) is co-cultured with natural killer cells (effector cells) in an E / T ratio of 1 / 3. Figure 25 shows the results of cancer cell viability according to treatment with combined GI-101 or CD80-Fc+Fc-IL2v2 material when an A549 cell line is co-cultured with natural killer cells in an E / T ratio = 1 / 1. Figure 26 shows the results of cancer cell viability according to treatment with combined GI-101 or CD80-Fc+Fc-IL2v2 material when an A549 cell line is co-cultured with natural killer cells in an E / T ratio = 3 / 1. Figure 27 shows the results of cancer cell viability according to treatment with combined GI-101 or CD80-Fc+Fc-IL2v2 material when an A549 cell line is co-cultured with natural killer cells in an E / T ratio = 10 / 1. Figure 28 is a schematic diagram showing an mGI-101 and / or NK cell combination therapy administration program to a CT26 transplanted mouse model of carcinoma. Figure 29 shows the results of the tumor growth inhibitory effect according to the co-administration of natural killer cells and mGI-101 to a CT26 transplanted mouse model of carcinoma. Figure 30 shows the percentage of tumor growth inhibitory effect according to the co-administration of natural killer cells and mGI-101 to a CT26 transplanted mouse model of carcinoma. Figure 31 shows tumor growth measurements of individual laboratory animals in each treatment group (vehicle, NK cell, mGI-101, NK cell + mGI-101) in a CT26 transplanted mouse model of carcinoma. Figure 32 shows tumor growth measurements of individual laboratory animals in the vehicle group in a CT26 transplanted mouse model of carcinoma. Figure 33 shows tumor growth measurements of individual laboratory animals in the NK cell treatment group in a CT26 transplanted mouse model of carcinoma. Figure 34 shows tumor growth measurements of individual laboratory animals in the mGI-101 treatment group in a CT26 transplanted mouse model of carcinoma. Figure 35 shows tumor growth measurements of individual laboratory animals in the natural killer cell and mGI-101 co-administration group in a CT26 transplanted mouse model of carcinoma. Best Way to Carry Out the Invention One aspect of the present invention provides a pharmaceutical composition that includes, as active ingredients, a fusion protein comprising a CD80 protein and an IL-2 protein, and NK cells. One aspect of the present invention provides a pharmaceutical composition that includes, as active ingredients, a fusion protein comprising a CD80 protein and an IL-2 protein, and NK cells. Natural killer cell As used herein, the term NK cell refers to a natural killer cell (hereafter referred to as an NK cell) and is one of the innate immune cells that interacts directly with various macrophages and T lymphocytes or generates cytokines to regulate immune responses and, by 6 CAzann / zznz / E / YiAi Consequently, it plays an important role in autoimmune diseases. In the present invention, NK cells can be isolated from the spleen or bone marrow, but are not limited to these. Specifically, NK cells can be obtained from autologous or heterologous cells. Additionally, NK cells can be derived from mammals or humans. Preferably, they can be obtained from an individual who intends to receive NK cell therapy. In this case, NK cells can be isolated directly from an individual's blood and used, or immature NK cells or stem cells obtained from the individual can be differentiated and used. Additionally, natural killer cells can be obtained through the following steps, which include: i) isolating cells that do not express CD3 from peripheral blood mononuclear cells (PBMCs); ii) isolating cells that express CD56 from cells that do not express CD3 that were isolated in the previous step; and iii) culturing an isolated cell in the presence of a fusion protein dimer comprising IL-2 or a variant thereof and CD80 or a fragment thereof. Additionally, natural killer cells can be obtained through the following steps which include: i) isolating cells that do not express CD3 from PBMCs; and ii) culturing the isolated cells in the presence of a fusion protein dimer comprising IL-2 or a variant thereof and CD80 or a fragment thereof. In addition, natural killer cells can be obtained through the following steps which include: i) isolating cells that do not express CD56 from PBMCs; and ii) culturing the isolated cells in the presence of a fusion protein dimer comprising IL-2 or a variant thereof and CD80 or a fragment thereof. A fusion protein dimer comprising an IL-2 protein and a CD80 protein As used herein, the term IL-2 or interleukin-2, unless otherwise specified, refers to any naturally occurring IL-2 obtained from any vertebrate source, including mammals, e.g., primates (such as humans) and rodents (such as mice and rats). IL-2 may be derived from animal cells and also includes IL-2 derived from recombinant cells that can produce IL-2. Additionally, IL-2 may be wild-type IL-2 or a variant thereof. In this specification, IL-2 or a variant thereof may be collectively referred to as IL-2 protein or IL-2 polypeptide. IL-2, an IL-2 protein, an IL-2 polypeptide, and an IL-2 variant bind specifically, for example, to an IL-2 receptor. This specific binding can be identified by methods known to those skilled in the art. One form of IL-2 may have the amino acid sequence of SEQ ID NO: 35 or SEQ ID NO: 36. Here, IL-2 may also be in a mature form. Specifically, mature IL-2 may not comprise a signal sequence and may have the amino acid sequence of SEQ ID NO: 10. Here, IL-2 may be used under a concept that encompasses a fragment of wild-type IL-2 in which a portion of the N-terminal or C-terminal end of the wild-type IL-2 is truncated. Additionally, the IL-2 fragment may be in a form in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 continuous amino acids are truncated from the N-terminus of a protein having the amino acid sequence of SEQ ID NO: 35 or SEQ ID NO: 36. Additionally, the IL-2 fragment may be in a form in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 continuous amino acids are truncated from the C-terminal of a protein having the amino acid sequence of SEQ ID NO: 35 or SEQ ID NO: 36. As used in this description, the term IL-2 variant refers to a form in which a portion of the amino acids of full-length IL-2 or the IL-2 fragment described above is substituted. That is, an IL-2 variant may have a different amino acid sequence from wild-type IL-2 or a fragment thereof. However, an IL-2 variant may have activity equivalent to or similar to wild-type IL-2. Here, IL-2 activity may, for example, refer to specific binding to an IL-2 receptor, the specific binding of which can be measured using methods known to those skilled in the art. Specifically, a variant of IL-2 can be obtained by substituting a portion of amino acids in wild-type IL-2. One modality of the IL-2 variant obtained by amino acid substitution can be obtained by substituting at least one of the 38th, 42nd, 45th, 61st, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Specifically, the IL-2 variant can be obtained by substituting at least one of the 38th, 42nd, 45th, 61st, or 72nd amino acids in the amino acid sequence of SEQ ID NO: 10 with another amino acid. Additionally, when IL-2 is in a form where a portion of the N-terminus in the amino acid sequence of SEQ ID NO: 35 is truncated, the amino acid at a position complementary to that in the amino acid sequence of SEQ ID NO: 10 can be substituted with another amino acid. For example, when IL-2 has the amino acid sequence of SEQ ID NO: 35, its IL-2 variant can be obtained by substituting at least one of the 58th, 62nd, 65th, 81st, or 92nd amino acid in the amino acid sequence of SEQ ID NO: 35 with another amino acid. These amino acid residues correspond to the 38th, 42nd, 45th, 61st, and 72nd amino acid residues in the amino acid sequence of SEQ ID NO: 10, respectively. According to one modality, one, two, three, four, five, six, seven, eight, nine, or ten amino acids may be substituted, provided that the IL-2 variant maintains IL-2 activity. According to another modality, one to five amino acids may be substituted. In one embodiment, an IL-2 variant can be in a form in which two amino acids are substituted. Specifically, the IL-2 variant can be obtained by substituting the 38th and 42nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 38th and 45th amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 38th and 61st amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 38th and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 42nd and 45th amino acids in the amino acid sequence of SEQ ID NO: 10.Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 42nd and 61st amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 42nd and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 45th and 61st amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 45th and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 61st and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Furthermore, a variant of IL-2 may exist in a form in which three amino acids are substituted. Specifically, the IL-2 variant may be obtained by substituting the 38th, 42nd, and 45th amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant may be obtained by substituting the 38th, 42nd, and 61st amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant may be obtained by substituting the 38th, 42nd, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant may be obtained by substituting the 38th, 45th, and 61st amino acids in the amino acid sequence of SEQ ID NO: 10. CAzann / zznz / E / YiAi Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 38th, 45th, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 38th, 61st, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 42nd, 45th, and 61st amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 42nd, 45th, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 45th, 61st, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, a variant of IL-2 may be in a form in which four amino acids are substituted. Specifically, the IL-2 variant can be obtained by substituting the 38th, 42nd, 45th, and 61st amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 38th, 42nd, 45th, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 38th, 45th, 61st, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 38th, 42nd, 61st, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10. Additionally, in one embodiment, the IL-2 variant can be obtained by substituting the 42nd, 45th, 61° and 72° amino acids in the amino acid sequence of SEQ ID NO: 10.Furthermore, a variant of IL-2 can exist in a form where five amino acids are substituted. Specifically, the IL-2 variant can be obtained by substituting each of the 38th, 42nd, 45th, 61st, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10 with another amino acid. Here, the other amino acid introduced by substitution can be any one selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. However, with respect to amino acid substitution by the IL-2 variant, in the amino acid sequence of SEQ ID NO: 10, the 38th amino acid cannot be substituted with arginine, the 42nd amino acid cannot be substituted with phenylalanine, the 45th amino acid cannot be substituted with tyrosine, the 61st amino acid cannot be substituted with glutamic acid, and the 72nd amino acid cannot be substituted with leucine. Regarding the substitution of amino acids by an IL-2 variant, in the amino acid sequence of SEQ ID NO: 10, the 38th amino acid, arginine, can be substituted with an amino acid 10 CAzann / zznz / E / YiAi other than arginine. Preferably, with respect to the substitution of amino acids by an IL-2 variant, in the amino acid sequence of SEQ ID NO: 10, the 38th amino acid arginine may be substituted with alanine (R38A). With regard to the substitution of amino acids by an IL-2 variant, in the amino acid sequence of SEQ ID NO: 10, the 42nd amino acid, phenylalanine, may be substituted with an amino acid other than phenylalanine. Preferably, with regard to the substitution of amino acids by an IL-2 variant, in the amino acid sequence of SEQ ID NO: 10, the 42nd amino acid, phenylalanine, may be substituted with alanine (F42A). With regard to the substitution of amino acids by an IL-2 variant, in the amino acid sequence of SEQ ID NO: 10, the 45th amino acid, tyrosine, may be substituted with an amino acid other than tyrosine. Preferably, with regard to the substitution of amino acids by an IL-2 variant, in the amino acid sequence of SEQ ID NO: 10, the 45th amino acid, tyrosine, may be substituted with alanine (Y45A). With regard to the substitution of amino acids by an IL-2 variant, in the amino acid sequence of SEQ ID NO: 10, the 61st amino acid, glutamic acid, may be substituted with an amino acid other than glutamic acid. Preferably, with regard to the substitution of amino acids by an IL-2 variant, in the amino acid sequence of SEQ ID NO: 10, the 61st amino acid, glutamic acid, may be substituted with arginine (E61R). With regard to the substitution of amino acids by an IL-2 variant, in the amino acid sequence of SEQ ID NO: 10, the 72nd amino acid, leucine, may be substituted with an amino acid other than leucine. Preferably, with regard to the substitution of amino acids by an IL-2 variant, in the amino acid sequence of SEQ ID NO: 10, the 72nd amino acid, leucine, may be substituted with glycine (L72G). Specifically, an IL-2 variant can be obtained by at least one substitution selected from the group consisting of R38A, F42A, Y45A, E61R and L72G, in the amino acid sequence of SEQ ID NO: 10. Specifically, an IL-2 variant can be obtained by substitutions of amino acids at two, three, four, or five positions among the positions selected from the group consisting of R38A, F42A, Y45A, E61R, and L72G. Additionally, an IL-2 variant can exist in a form where two amino acids are substituted. Specifically, an IL-2 variant can be obtained by substitutions at R38A and F42A. Additionally, in one embodiment, an IL-2 variant can be obtained by substitutions at R38A and Y45A. Additionally, in one embodiment, an IL-2 variant can be obtained by substitutions at R38A and E61R. Additionally, in one embodiment, an IL-2 variant can be obtained by substitutions at R38A and L72G. Additionally, in one embodiment, an IL-2 variant can be obtained by substitutions at F42A and Y45A. Additionally, in one embodiment, an IL-2 variant can be obtained by substitutions at F42A and E61R. Additionally, in one embodiment, an IL-2 variant can be obtained by substitutions at F42A and L72G. Additionally, in one modality, a variant of IL-2 can be obtained by the E61R and L72G substitutions. Furthermore, a variant of IL-2 can exist in a form where three amino acids are substituted. Specifically, a variant of IL-2 can be obtained by substitutions at R38A, F42A, and Y45A. Additionally, in one embodiment, a variant of IL-2 can be obtained by substitutions at R38A, F42A, and E61R. Additionally, in one embodiment, a variant of IL-2 can be obtained by substitutions at R38A, F42A, and L72G. Additionally, in one embodiment, a variant of IL-2 can be obtained by substitutions at R38A, Y45A, and E61R. Additionally, in one embodiment, a variant of IL-2 can be obtained by substitutions at R38A, Y45A, and L72G. Additionally, in one embodiment, a variant of IL-2 can be obtained by substitutions at F42A, Y45A, and E61R. Additionally, in one modality, a variant of IL-2 can be obtained by the substitutions F42A, Y45A and L72G.Additionally, in one embodiment, an IL-2 variant can be obtained by the substitutions F42A, E61R, and L72G. Additionally, in one embodiment, an IL-2 variant can be obtained by the substitutions Y45A, E61R, and L72G. Additionally, a variant of IL-2 can exist in a form where four amino acids are substituted. Specifically, a variant of IL-2 can be obtained by substituting R38A, F42A, Y45A, and E61R. Furthermore, in one embodiment, a variant of IL-2 can be obtained by substituting R38A, F42A, Y45A, and L72G. In addition, a variant of IL-2 can be obtained by the substitutions R38A, F42A, Y45A, E61R and L72G. Preferably, a modality of the IL-2 variant may comprise any that is selected from the following combinations of substitutions (a) to (d) in the amino acid sequence of SEQIDNO: 10: (a) R38A / F42A; (b) R38A / F42A / Y45A; (c) R38A / F42A / E61R; or (d) R38A / F42A / L72G. Here, when IL-2 has the amino acid sequence of SEQ ID NO: 35, an amino acid substitution may be present at a position complementary to that of the amino acid sequence of SEQ ID NO: 10. Additionally, even when IL-2 is a fragment of the amino acid sequence of SEQ ID NO: 35, an amino acid substitution may be present at a position complementary to that of the amino acid sequence of SEQ ID NO: 10. Specifically, the IL-2 variant may have the amino acid sequence of SEQ ID NO: 6, 22, 23 or 24. Additionally, the IL-2 variant can be characterized by its low in vivo toxicity. This low in vivo toxicity may be a side effect of IL-2 binding to the alpha chain of the IL-2 receptor (IL-2Ra). Several IL-2 variants have been developed to improve upon this side effect of IL-2 binding to IL-2Ra, and these IL-2 variants may be described in U.S. Patent No. 5,229,109 and Korean Patent No. 1,667,096. In particular, the IL-2 variants described in this application have a low binding capacity to the alpha chain of the IL-2 receptor (IL-2Ra) and, therefore, exhibit lower in vivo toxicity than wild-type IL-2. As used herein, the term CD80, also called B7-1, is a membrane protein present on dendritic cells, activated B lymphocytes, and monocytes. CD80 provides costimulatory signals essential for T lymphocyte activation and survival. CD80 is known as a ligand for the two different proteins, CD28 and CTLA-4, present on the surface of T lymphocytes. CD80 consists of 288 amino acids and may specifically have the amino acid sequence SEQ ID NO: 11. Additionally, as used herein, the term CD80 protein refers to either the full-length CD80 or a fragment of CD80. As used in this description, the term CD80 fragment refers to a truncated form of CD80. Additionally, the CD80 fragment may be an extracellular domain of 13 CAzann / zznz / E / YiAi CD80. One modality of the CD80 fragment can be obtained by removing the N-terminus amino acids Ioa 34° which are a CD80 signal sequence. Specifically, one modality of the CD80 fragment can be a protein consisting of amino acids 35° to 288° in SEQ ID NO: 11. Additionally, one modality of the CD80 fragment can be a protein consisting of amino acids 35° to 242° in SEQ ID NO: 11. Additionally, one modality of the CD80 fragment can be a protein consisting of amino acids 35° to 232° in SEQ ID NO: 11. Additionally, one modality of the CD80 fragment can be a protein consisting of amino acids 35° to 139° in SEQ ID NO: 11. Additionally, one modality of the CD80 fragment can be a protein consisting of amino acids 142° to 242° in SEQ ID NO: 11. In one modality, a CD80 fragment can have the amino acid sequence of SEQ ID NO: 2.Additionally, the IL-2 protein and the CD80 protein can be linked to each other by means of a linker or a carrier. Specifically, IL-2 or a variant thereof and CD80 (B7-1) or a fragment thereof can be linked to each other by means of a linker or a carrier. In this description, the linker and the carrier may be used interchangeably. The linker joins two proteins. One form of the linker may include 1 to 50 amino acids, albumin or a fragment thereof, an Fe domain of an immunoglobulin, or the like. Herein, the Fe domain of an immunoglobulin refers to a protein comprising the heavy chain constant region 2 (CH2) and the heavy chain constant region 3 (CH3) of an immunoglobulin, and does not comprise the heavy and light chain variable regions and the light chain constant region 1 (CH1) of an immunoglobulin. The immunoglobulin may be IgG, IgA, IgE, IgD, or IgM, and preferably IgG4. Herein, the Fe domain of wild-type immunoglobulin G4 may have the amino acid sequence SEQ ID NO: 4. Additionally, the Fe domain of an immunoglobulin can be a variant of the Fe domain as well as a wild-type Fe domain. Furthermore, as used herein, the term Fe domain variant can refer to a form that differs from the wild-type Fe domain in terms of glycosylation pattern, having high glycosylation compared to the wild-type Fe domain, or having low glycosylation compared to the wild-type Fe domain, or a deglycosylated form. Additionally, an aglycosylated Fe domain is included. The Fe domain or a variant thereof can be engineered to have an adjusted number of sialic acids, fucosylations, or glycosylations through culture conditions or genetic modification of a host. Additionally, the glycosylation of the Fe domain of an immunoglobulin can be modified by conventional methods, such as chemical methods, enzymatic methods, and genetic engineering methods using microorganisms. Furthermore, the Fe domain variant can be a mixed form of Fe regions from immunoglobulins IgG, IgA, IgE, IgD, and IgM. Additionally, the Fe domain variant can be in a form where some amino acids of the Fe domain are substituted with other amino acids. One form of the Fe domain variant may have the amino acid sequence SEQ ID NO: 12. The fusion protein may have a structure in which, by using an Fe domain as a linker (or carrier), a CD80 protein and an IL-2 protein, or an IL-2 protein and a CD80 protein, are linked to the N and C ends of the fusion protein (Figure 1). The link between the N-terminal or C-terminal end of the Fe domain and CD-80 or IL-2 may optionally be achieved by means of a linker peptide. Specifically, a fusion protein may consist of the following structural formula (I) or (II): N'-X-[linker (l)]n-domain Fc-[linker (2)]mYC (I) Ν'-Y-[linker (l)]n-domain Fc-[linker (2)]mXC (II) Here, in structural formulas (I) and (II), N' is the N-terminus of the fusion protein, C is the C-terminus of the fusion protein, X is a CD80 protein, And it is an IL-2 protein, the linkers (1) and (2) are peptide linkers, and ynym are each independently 0 or 1. Preferably, the fusion protein may consist of structural formula (1). The IL-2 protein is as described above. Additionally, the CD80 protein is as described above. According to one embodiment, the IL-2 protein may be a variant of IL-2 with one to five amino acid substitutions compared to wild-type IL-2. The CD80 protein may be a fragment obtained by truncating up to approximately 34 continuous amino acid residues from either the N-terminal or C-terminal end of wild-type CD80. Alternatively, the CD80 protein may be an extracellular immunoglobulin-like domain that has the activity of binding to the T-cell surface receptors CTLA4 and CD28. Specifically, the fusion protein may have the amino acid sequence of SEQ ID NO: 9, 26, 28, or 30. According to another modality, the fusion protein includes a polypeptide that has a sequence identity of 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with the amino acid sequence of SEQ ID NO: 9, 26, 28, or 30. Here, identity is, for example, the percentage of homology and can be determined through a homology comparison program such as the BlastN program of the National Center for Biotechnology Information (NCBI). The peptide linker (1) may be located between the CD80 protein and the Fe domain. The peptide linker (1) may consist of 5 to 80 continuous amino acids, 20 to 60 continuous amino acids, 25 to 50 continuous amino acids, or 30 to 40 continuous amino acids. In one embodiment, the peptide linker (1) may consist of 30 amino acids. Additionally, the peptide linker (1) may comprise at least one cisterna. Specifically, the peptide linker (1) may comprise one, two, or three cisternae. Additionally, the peptide linker (1) may be derived from the hinge of an immunoglobulin. In one embodiment, the peptide linker (1) may be a peptide linker consisting of the amino acid sequence SEQ ID NO: 3. The peptide linker (2) can consist of 1 to 50 consecutive amino acids, 3 to 30 consecutive amino acids, or 5 to 15 consecutive amino acids. In one embodiment, the peptide linker (2) can be (G4S)n (where n is an integer from 1 to 10). Here, in (G4S)nN, n can be 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In one embodiment, the peptide linker (2) can be a peptide linker consisting of the amino acid sequence SEQ ID NO: 5. In another aspect of the present invention, a pharmaceutical composition is provided that includes, as an active ingredient, a dimer obtained by joining two fusion proteins, each comprising an IL-2 protein and a CD80 protein, and an NK cell. The fusion protein comprising IL-2 or a variant thereof and CD80 or a fragment thereof is as described above. Here, the union between the fusion proteins that constitute the dimer can be, but is not limited to, a disulfide bond formed by cisternae present in the linker. The fusion proteins that constitute the dimer can be identical or different fusion proteins. Preferably, the dimer can be a homodimer. One modality of the fusion protein that constitutes the dimer can be a protein having the amino acid sequence SEQ ID NO: 9. In the present invention, cancer may be any selected from the group consisting of gastric cancer, liver cancer, lung cancer, colorectal cancer, breast cancer, prostate cancer, ovarian cancer, pancreatic cancer, cervical cancer, thyroid cancer, laryngeal cancer, acute lymphoblastic leukemia, brain tumor, neuroblastoma, retinoblastoma, head and neck cancer, salivary gland cancer, and lymphoma. A preferred dosage of the pharmaceutical composition varies depending on the patient's condition and body weight, the severity of the disease, the drug form, the route and duration of administration, and may be appropriately selected by those skilled in the art. In the pharmaceutical composition for treating or preventing cancer of the present invention, the active ingredient may be comprised in any amount (effective amount) depending on the application, use, dosage form, purpose of the mixture, and the like, provided that the active ingredient can exhibit anticancer activity. A conventional effective amount thereof shall be determined within a range of 0.001% to 20.0% by weight, based on the total weight of the composition. Herein, the term "effective amount" refers to an amount of an active ingredient that can induce an anticancer effect.Such an effective quantity can be determined experimentally within the scope of the common knowledge of experts in the technique. As used herein, the term “treatment” can refer to both therapeutic and prophylactic treatment. Here, prophylaxis can mean the relief or mitigation of a pathological condition or disease in an individual. In one sense, the term “treatment” includes both the application and any form of administration to treat a disease in a mammal, including a human. Additionally, the term includes inhibiting or slowing a disease or its progression; and includes the meanings of restoring or repairing damaged or lost functions so that a disease is partially or completely relieved; stimulating inefficient processes; or alleviating a serious illness. As used herein, the term “efficacy” refers to the capacity that can be determined by one or more parameters, for example, survival or disease-free survival over a certain period of time, such as one year, five years, or ten years. Additionally, the parameter may include the reduction in the size of at least one tumor in an individual. Pharmacokinetic parameters such as bioavailability and underlying parameters such as clearance rate can also affect efficacy. Therefore, “enhanced efficacy” (e.g., improved efficacy) may be due to improved pharmacokinetic parameters and enhanced efficacy, which can be measured by comparing clearance rate and tumor growth. CAzann / zznz / E / YiAi in laboratory animals or human subjects, or when comparing parameters such as survival, recurrence, or disease-free survival. As used herein, the term therapeutically effective amount or pharmaceutically effective amount refers to a quantity of a compound or composition effective in preventing or treating the disease in question, sufficient to treat the disease with a reasonable risk / benefit ratio, applicable to medical treatment, and not causing adverse effects. A level of effective amount can be determined based on factors including the patient's health status, the type and severity of the disease, the drug's activity, the patient's sensitivity to the drug, the mode of administration, the timing of administration, the route of administration and excretion rate, the duration of treatment, the formulation or drugs used concurrently, and other factors well-known in the medical field. In one modality, the therapeutically effective amount means a quantity of drug effective in treating cancer.Here, the pharmaceutical composition may additionally include a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may be any carrier provided it is a non-toxic substance suitable for administration to a patient. Distilled water, alcohol, fat, wax, and inert solids may be used as carriers. The pharmaceutical composition may also contain a pharmaceutically acceptable adjuvant (buffer, dispersant). Specifically, by including a pharmaceutically acceptable carrier in addition to the active ingredient, the pharmaceutical composition can be prepared in a parenteral formulation, depending on its route of administration, using conventional methods known in the art. Here, the term pharmaceutically acceptable means that the carrier has no more toxicity than the patient can tolerate without inhibiting the activity of the active ingredient. When the pharmaceutical composition is prepared in a parenteral formulation, it can be converted into preparations in the form of injections, transdermal patches, nasal inhalants, or suppositories using suitable carriers according to methods known in the art. For injections, suitable carriers may include sterile water, ethanol, polyols such as glycerol or propylene glycol, or a mixture thereof; and preferably an isotonic solution, such as Ringer's solution, phosphate-buffered saline (PBS) containing triethanolamine, or sterile water for injection and 5% dextrose, or similar solutions. The formulation of pharmaceutical compositions is known in the art, and reference may be made specifically to Remington's Pharmaceutical Sciences (19th ed., 1995) and similar publications. This document is considered part of the present description. A preferred dose of a dimer in the pharmaceutical composition may range from 0.01 pg / kg to 10 g / kg, or 0.01 mg / kg to 1 g / kg, per day, depending on the patient's condition, body weight, sex, age, severity of illness, and route of administration. The dose may be administered once daily or divided into several doses per day. This dose shall not be interpreted as limiting the scope of the present invention in any respect. Additionally, the NK cells in the pharmaceutical composition may be administered in a quantity of 100 to 1000 cells, 100 to 1.500 cells, with appropriate adjustment within the range that exhibits a pharmacological effect. The subjects to whom the pharmaceutical composition may be applied (prescribed) are mammals and humans, with humans being particularly preferred. In addition to the active ingredient, the pharmaceutical composition of this application may also include any compound or natural extract whose safety has already been validated and which is known to have anticancer activity, to enhance or reinforce the anticancer activity. In another aspect of the present invention, a fusion protein dimer comprising an IL-2 protein and a CD80 protein, and an NK cell, are used to treat cancer. In another aspect of the present invention, a fusion protein dimer comprising an IL-2 protein and a CD80 protein, and NK cells, are used to enhance a therapeutic effect on cancer. In another aspect of the present invention, the use of a fusion protein dimer comprising an IL-2 protein and a CD80 protein and NK cells is provided for the manufacture of a drug for treating cancer. In another aspect of the present invention, a method for treating cancer and / or a method for enhancing a therapeutic effect on cancer is provided, which includes administering to a subject a fusion protein comprising an IL-2 protein and a CD80 protein or a fusion protein dimer where the two fusion proteins are linked, and an NK cell. Here, the fusion protein dimer and NK cells can be administered simultaneously or sequentially. In this case, the order of administration can be determined so that the administration of the fusion protein dimer is followed by the administration of NK cells, or vice versa. The subject may be an individual suffering from cancer or an infectious disease. Additionally, the subject may be a mammal, preferably a human. The 19 protein CAzann / zznz / E / YiAi fusion comprising an IL-2 protein and a CD80 protein, or the fusion protein dimer in which the two fusion proteins are linked are as described above. The route of administration, dosage, and frequency of administration of the fusion protein or fusion protein dimer and NK cells may vary depending on the patient's condition and the presence or absence of side effects. Therefore, the fusion protein or fusion protein dimer may be administered to a subject in various forms and quantities. The optimal method of administration, dosage, and frequency of administration may be selected within an appropriate range by those skilled in the art. Additionally, the fusion protein or fusion protein dimer may be administered in combination with other drugs or physiologically active substances whose therapeutic effect is known with respect to a disease being treated, or they may be formulated as combination preparations with other drugs. Due to IL-2 activity, the fusion protein in one embodiment of the present invention can activate immune cells such as natural killer cells. Therefore, the fusion protein can be used effectively for cancer and infectious diseases. In particular, it was identified that, compared to the wild type, an IL-2 variant with two to five amino acid substitutions, specifically an IL-2 variant comprising amino acid substitutions at two, three, four, or five positions among the positions selected from the group consisting of R38A, F42A, Y45A, E61R, and L72G, has a low binding capacity for the alpha chain of the IL-2 receptor and thus exhibits improved characteristics with respect to the pharmacological side effects of conventional IL-2.Therefore, such a variant of IL-2, when used alone or in the form of a fusion protein, may decrease the incidence of vascular (or capillary) leak syndrome (VLS), a problem conventionally associated with IL-2. METHOD FOR THE INVENTION The present invention will be described in more detail below by means of the following examples. However, the following examples are provided solely for the purpose of illustrating the present invention and the scope of the present invention is not limited to them. I. Preparation of a fusion protein dimer comprising IL-2 and CD80 Preparatory Example 1. Preparation of an hCD80-Fc-IL-2 (2M) variant: GI-101 To produce a fusion protein comprising a human CD80 fragment, an Fe domain and an IL-2 variant, a polynucleotide including a nucleotide sequence (SEQ ID NO: 8) encoding a fusion protein containing a signal peptide (SEQ ID NO: 1), a 20-strand fragment CAzann / zznz / E / YiAi CD80 (SEQ ID NO: 2), a linker-linked Ig hinge (SEQ ID NO: 3), an Fe domain (SEQ ID NO: 4), a linker (SEQ ID NO: 5), and an IL-2 (2M) variant in which two amino acids (R38A, F42A) (SEQ ID NO: 6) are substituted in this order from the N-terminal end were synthesized through the Invitrogen GeneArt gene synthesis service of ThermoFisher Scientific Inc., and cloned into a pcDNA3_4 vector. The vector was then introduced into CHO cells (EXPICHO™) to express a fusion protein (SEQ ID NO: 9). After vector introduction, the CHO cells were cultured at 37°C, 125 RPM, and 8% CO2 for 7 days and then harvested for fusion protein purification. The purified fusion protein dimer was named GI-101. Purification was performed using chromatography with the MabSelect SuRe protein resin. The fusion protein was bound under conditions of 25 mM Tris, 25 mM NaCl, and pH 7.4. It was then eluted with 100 mM NaCl and 100 mM acetic acid at pH 3. After adding 1 M 20% TrisHCl to a collection tube at pH 9, the fusion protein was collected. The collected fusion protein was dialyzed in PBS buffer for 16 hours. The absorbance at a wavelength of 280 nm was then measured over time using size exclusion chromatography with a TSKgel G3000SWXL column (TOSOH Bioscience) to obtain a high concentration of fusion protein. The isolated and purified fusion protein was then subjected to SDS-PAGE under reducing (R) or non-reducing (NR) conditions and stained with Coomassie blue to confirm its purity (Figure 2). The fusion protein was confirmed to be present at a concentration of 2.78 mg / ml, as detected using NanoDrop. The results obtained using size exclusion chromatography are shown in Figure 3. Preparatory Example 2. Preparation of an Fc-IL-2 (2M) variant dimer: Fc-IL-2v2 To produce a fusion protein comprising an Fe domain and an IL-2 variant, a polynucleotide including a nucleotide sequence (SEQ ID NO: 45) encoding a fusion protein containing a signal peptide (SEQ ID NO: 1), an Ig hinge (SEQ ID NO: 38), an Fe domain (SEQ ID NO: 4), a linker (SEQ ID NO: 5), and an IL-2 (2M) variant in which two amino acids (R38A, F42A) (SEQ ID NO: 6) are substituted in this order from the N-terminal end was synthesized through the Invitrogen GeneArt gene synthesis service of ThermoFisher Scientific Inc., and cloned into a pcDNA3_4 vector. Additionally, the vector was introduced into CHO cells (EXPI-CHO™) to express a fusion protein of SEQ ID NO: 44. After vector introduction, the CHO cells were cultured in an environment of 37 °C, 125 RPM, and 8% CO2 for several days and then harvested to purify a fusion protein dimer. The purified fusion protein dimer was named Fc-IL2v2. The purification and collection of the fusion protein were performed in the same manner as in Preparatory Example 1. The isolated and purified fusion protein was subjected to SDS-PAGE under reducing (R) or non-reducing (NR) conditions and stained with Coomassie blue to confirm its purity (Figure 4). The results confirmed that the fusion protein forms a dimer. Additionally, the results analyzed using size exclusion chromatography are shown in Figure 5. Preparatory Example 3. Preparation of an hCD80-Fc dimer: hCD80-Fc To produce a fusion protein comprising a human CD80 fragment and an Fe domain, a polynucleotide (SEQ ID NO: 39) including a nucleotide sequence encoding a fusion protein containing a signal peptide (SEQ ID NO: 1), a CD80 fragment (SEQ ID NO: 2), a linker-bound Ig hinge (SEQ ID NO: 3), an Fe domain (SEQ ID NO: 4), in this order from the N-terminal end was synthesized through the Invitrogen GeneArt gene synthesis service of ThermoFisher Scientific Inc., and cloned into a pcDNA3_4 vector. Additionally, the vector was introduced into CHO cells (EXPI-CHO™) to express a fusion protein of SEQ ID NO: 40. After vector introduction, the CHO cells were cultured in an environment of 37 °C, 125 RPM, and 8% CO2 for 7 days and then harvested to purify a fusion protein dimer. The purified fusion protein dimer was named hCD80Fc. Purification was performed using chromatography with the MabSelect SuRe protein resin. The fusion protein was bound under conditions of 25 mM Tris, 25 mM NaCl, and pH 7.4. It was then eluted with 100 mM NaCl and 100 mM acetic acid at pH 3. After adding 1 M 20% TrisHCl to a collection tube at pH 9, the fusion protein was collected. The collected fusion protein was dialyzed in PBS buffer for 16 hours. The absorbance at a wavelength of 280 nm was then measured over time using size exclusion chromatography with a TSKgel G3000SWXL column (TOSOH Bioscience) to obtain a high concentration of the fusion protein. The isolated and purified fusion protein was then subjected to SDS-PAGE under reducing (R) or non-reducing (NR) conditions and stained with Coomassie blue to confirm its purity (Figure 6). The results confirmed that the fusion protein forms a dimer. The results obtained using size exclusion chromatography are shown in Figure 7. Preparatory Example 4. Preparation of the mCD80-Fc-IL-2 (2M) variant: mGIlOl Following the same method as in Preparatory Example 1, a GI-101 type mouse comprising a mouse-derived CD80 and IL-2 was fabricated. Specifically, to produce a fusion protein comprising a mouse CD80, an Fe domain, and an IL-2 variant, a polynucleotide was synthesized through the Invitrogen GeneArt gene synthesis service from Thermo Fisher Scientific. The polynucleotide comprises a nucleotide sequence (SEQ ID NO: 14) encoding a fusion protein comprising a signal peptide (SEQ ID NO: 1), an mCD80 (SEQ ID NO: 13), a linker-linked Ig hinge (SEQ ID NO: 3), an Fe domain (SEQ ID NO: 4), a linker (SEQ ID NO: 5), and an IL-2 (2M) variant (R38A, F42A) (SEQ ID NO: 6) with two amino acid substitutions, in that order, from the N-terminus. The polynucleotide was inserted into the pcDNA3_4 vector. Additionally, the vector was introduced into CHO cells (EXPICHO™) to express the fusion protein of SEQ ID NO: 47.After vector introduction, the culture was grown for 7 days at 37 °C, 125 RPM, and 8% CO2. The culture was then harvested, and the fusion protein was purified from it. The purified fusion protein was designated mGIlOl. II. Preparation and culture of NK cells Example of preparation 1. Isolation of peripheral blood mononuclear cells (PBMCs) derived from CD3(-)CD56(+) natural killer cells To obtain CD3(-) cells, the number of PBMCs (peripheral blood mononuclear cells, Zen-Bio. Inc., NC 27709, USA, Cat#: SER-PBMC-200-F) was measured using an automated ADAM-MC2 cell counter (NanoEnTek, purchased from Cosmo Genetech Co., Ltd.). The PBMCs were transferred to a new tube and then centrifuged at 300 x g for 5 minutes at 4 °C. 0.5% (v / v) bovine serum albumin (BSA) and 2 mM EDTA were added to PBS to prepare MACS buffer (pH 7.2). After centrifugation, a cell pellet was treated with 80 ml of MACs buffer and 20 µA of CD3 magnetic beads (Miltenyi Biotech, 130-050-101) per 10⁷ cells to resuspend, and then reacted at 4 °C for 15 minutes. 10 ml of MACs buffer was added for washing, and the pellet was centrifuged at 300 x g for 10 minutes at 4 °C. The cell pellet was then resuspended in 0.5 ml of MACs buffer. First, 2 ml of MACs buffer were introduced into the LD column (Miltenyi Biotec, Bergisch Gladbach, Germany, Cat#: 130-042-901), and then the cell suspension was flowed through it. CD3(-) cells passing through the LD column were then collected. To collect the CD3(-) cells, 2 ml of MACs buffer was flowed through the column three times to ensure sufficient separation of the remaining cells. The collected CD3(-) cells were counted using a cell counter, then placed in a new tube and centrifuged at 300 x g for 5 minutes at 4 °C. The supernatant was then removed and 80 μA of MACs buffer and 20 pl of CD56 magnetic beads (Miltenyi biotech, Cat#: 130050-401) were added per 1xlO7 cells, followed by the reaction at a temperature of 4 °C for 15 minutes.Ten milliliters of MACs buffer were added for washing, and the cells were centrifuged at 300 x g for 10 minutes at 4 °C. The resulting cell pellet was then resuspended in 0.5 milliliters of MACs buffer. Three milliliters of MACs buffer were first introduced into the LS column (Miltenyi Biotec, Bergisch Gladbach, Germany, Cat#: 130-042-901), and the cell suspension was then flowed through. At this point, two milliliters of MACs buffer were flowed through three times to allow sufficient separation of the remaining cells in the LS column. After the LS column was removed from a magnetic support, five milliliters of MACs buffer were added, and pressure was applied using a piston to obtain the CD3(-)CD56(+) natural killer cells. The obtained CD3()CD56(+) natural killer cells were placed in a new tube and centrifuged at 300 xg for 5 minutes at a temperature of 4 °C.After removing the supernatant, the cells were suspended in the culture medium and the number of suspended cells was measured using a cell counter. Example of preparation 2. Culture and obtaining CD3-CD56+ natural killer cells 100 µA of CD335 (NKp46)-biotin and 100 µA of CD2-biotin, included in an NK cell activation / expansion kit (Cat#: 130-112-968) (Miltenyi Biotec, Bergisch Gladbach, Germany), were placed in a 1.5 ml microtube and mixed. 500 µA of MACSiBead anti-biotin particles were added and mixed. Then, 300 µA of MACs buffer was added and mixed at 2–8 °C for 2 hours using a microtube rotator. Next, 5 μA of NK activation beads per 10⁶ cells were transferred to a new tube. 1 mL of PBS was added and centrifuged at 300 x g for 5 minutes. After removing the supernatant, RPMI1640 medium containing 5% human AB serum (Cat#: H4522) (Sigma, St. Louis, Missouri, USA) was added on a basis of 5 μA per 10⁶ NK cells and suspended beads, followed by inoculation into the CD3-CD56+ natural killer cells isolated in Example Preparation 1. Next, CD3-CD56+ natural killer cells were seeded in a 24-well plate and RPMI1640 medium containing 5% human AB serum (Cat#:H4522) (Sigma, St. Louis, Missouri, USA) and rhIL-2 (500 IU / ml) was added, followed by culture under conditions of 37 °C and 5% CO2. The number of cells to be subcultured was then determined every 2 days in the order of 12-well plate, 6-well plate and 25T flask when the cells occupied 80% or more of the culture vessel (confluence), and finally all cells were collected on day 21. Example of preparation 3. Culture and collection of mouse-derived natural killer cells Example of preparation 3.1. Preparation of mouse spleen and bone marrow cells To obtain mouse-derived natural killer cells, mouse spleen and bone marrow cells were first prepared. Specifically, the spleen and femur were removed from a 6-week-old female Balb / c (ORIENT BIO Inc.), and as much fat and muscle as possible was removed, taking care not to break the femur. The removed femur was placed in 70% ethanol, then into a 50 mL tube containing 5 mL of PBS, and the spleen was immediately transferred to a 50 mL tube containing 5 mL of PBS and then stored on ice. A 70-pm filter was overlapped onto a 50 mL tube containing 5 mL of FACS buffer and prepared for the spleen and bone marrow, respectively. The composition of FACS buffer A is as described in Table 1 below. [Table 1] Composition Volume Final Concentration Product Manufacturer FACS Buffer A FBS Hyclone 15 ml 3% EDTA Welgene 10 ml 10 mM HEPES Welgene 10 ml 20 mM Polymyxin B Merk 300 ml 10 g / ml Penicillin / Streptomycin Biolegend 5 ml 10,000 U / ml penicillin / 10,000 g / ml streptomycin 100 mM sodium pyruvate Gibco 5 ml 1 mM PBS Sigma for 500 ml After crushing the tissue with a syringe, 5 mL of FACS buffer A was added to collect the cells. The sample was then centrifuged at 1300 rpm for 5 minutes at 4°C, and the supernatant was discarded. The spleen was dissolved with 3 mL of ACK lysis buffer to remove red blood cells and then incubated on ice for 3 minutes. After 3 minutes, FACS buffer A was added to bring the total volume to 20 mL. The resulting solution was vortexed and then centrifuged at 1300 rpm for 5 minutes at 4°C, and the supernatant was discarded. Red blood cells were removed by repeating the above process until the pellet turned pink and were dissolved with 10 mL of FACS buffer A for cell counting. Both sides of the femur were cut into a 70 µm filter for bone marrow, and FACS buffer A was flowed into the bone holes using a 1 ml needle attached to a syringe filled with 10 ml of FACS buffer A while moving it back and forth. Cells were then collected while FACS buffer A was also flowed into the cut tissue. The cells were collected and then centrifuged at 1300 rpm for 5 minutes at 4°C. The supernatant was then removed and diluted with 10 ml of FACS buffer A, followed by cell counting. Example of preparation 3.2. Isolation and culture of mouse NK cells Using an NK cell isolation kit (No. 130-115-818), NK cells were isolated from the spleen and bone marrow of the 6-week-old female Balb / c mouse (ORIENT BIO Inc.) as described in Sample Preparation 3.1 above. After isolation, the cells were centrifuged at 1300 x g at 4 °C and the supernatant was discarded. Forty 10⁷ cells (600 µl for spleen, 200 µl for bone marrow) of MACS buffer were added to resuspend the cell pellet, followed by 10⁷ cells (150 µl for spleen, 50 µl for bone marrow) of NK cell cocktail. However, in this case, more than 5 × 10⁷ cells exhibited aggregation, so they were divided and mixed. Centrifugation was then performed at 300 × g at 4 °C, and the supernatant was discarded. Two milliliters of wash buffer were added per 10⁷ cells (30 milliliters for spleen, 10 milliliters for bone marrow), the cells were washed, centrifuged at 4°C at 300 x g, and the supernatant was discarded. Then, 80 µl of MACS buffer were added per 10⁷ cells (1.2 milliliters for spleen, 400 µl for bone marrow), followed by 20 µl of antibiotic microspheres per 10⁷ cells (300 µl for spleen, 100 µl for bone marrow), the mixture was combined, and the cells were incubated in a refrigerator for 10 minutes. Five hundred microliters of cells mixed with antibiotic microspheres were introduced into an MS column to obtain a supernatant that passed through the column. The same process was repeated to obtain the supernatant that passed through the column, and it was centrifuged at 4 °C at 300 x g. The supernatant was then discarded. The cells were counted upon resuspension in GC-RPMI (Ix) medium (spleen: 6.95 x 10⁵ / ml, 59% viability; bone marrow: 1.58 x 10⁶ / ml, 64% viability). The composition of GC-RPMI medium is as described in Table 2 below. [Table 2] Composition Final Concentration Product Manufacturer Cat.# GC-RPMI RPMI 1640 Welgene LM 011-01 Pen-Strep Welgene LS 202-02 lx Gentamicin Gibco 15750-060 50 pg / ml Sodium Pyruvate Welgene LS 013-01 1 mM 2-Mercaptoethanol Gibco 21985-023 55 μM NEAA Gibco 11140050 2 mM L-Glutamine Gibco 25030149 2 mM FBS Hyclone SH30084.03 10% CAzann / zznz / E / YiAi After seeding 3.5xl05 NK cells isolated from the spleen and bone marrow in a 60 mm culture vessel, they were treated with 50 ng / ml of rmIL-2 and cultured for 14 days. III. Preparation of cancer cells and construction of the mouse model Example of preparation 4. Preparation of a human carcinoma cell line and culture medium for this An appropriate culture solution was used for each cancer cell line with reference to Table 3 below. [Table 3] Cancer Cell Line Organism of Origin Disease Manufacturer Culture Medium Components K562 Homo sapiens, Human chronic myeloid leukemia ATCC RPMI 1640 + 10% FBS MDA-MB-231 Homo sapiens, Human breast cancer Korea Cell Line Bank RPMI 1640 high glucose + 10% FBS HCT-116 Homo sapiens, Human colon cancer ATCC McCoy's 5A + 10% FBS A549 Homo sapiens, Human lung cancer ATCC RPMI1640 + 10% FBS Specifically, 2 x 10⁶ cells from cancer cell lines were resuspended in 8 mL of each culture solution and cultured in a 25T flask. Upon cell recovery, 1 mL of trypsin-EDTA (0.25%) was treated and then reacted in 5% CO₂ for 2 minutes for adherent-type cells. Then, 5 mL of culture solution were added to recover any cells that had detached from the flask, and the cells were centrifuged at 300 x g for 5 minutes. Table 4 below shows culture solution compositions specific to each cancer cell line. [Table 4] CAzann / zznz / E / YiAi Composition Final Volume conc. Product Manufacturer Cat.# RPMI1640 (10% FBS) Core Components RPMI 1640 Medium (lx), Liquid Welgene LM011-01 500 ml FBS HYCLONE™ SV30207.0 2 50 ml 10% Penicillin-Streptomycin Solutions (X100) Welgene LS 202-02 0.5 ml lx High Glucose RPMI 1640 (10% FBS) Core Components RPMI 1640 High Glucose Medium ATCC 30-2001 500 ml FBS HYCLONE™ SV30207.0 2 50 ml 10% Penicillin-Streptomycin Solutions (x100) Welgene LS 202-02 0.5 ml lx McCoy (10% FBS) Core Components McCoy's 5A (ATCC) ATCC 30-2007 500 ml FBS HYCLONE™ SV30207.0 2 50 ml 10% Penicillin-Streptomycin Solutions (x100) Welgene LS 202-02 0.5 ml lx Example of preparation 5. Preparation of mouse-derived carcinoma cell line and culture medium CT26.WT, a Mus musculus colon carcinoma cell line, was purchased from ATCC (American Type Culture Collection, USA) (Table 5). The carcinoma cells to be used in the experiment were thawed, placed in a cell culture flask, and cultured at 37 °C in an incubator with 5% CO2 (MCO-170M, Panasonic, Japan). On the day of cell line transplantation, the cultured cells were placed in a centrifuge tube, collected, and then centrifuged at 125 x g for 5 minutes to remove the supernatant. PBS was then added to prepare the cell suspension (5 x 10⁷ cells / ml), dispensed into aliquots for 9 mice, and stored on ice until administration. [Table 5] Organism of origin Disease Manufacturer Final concentration CT26 Mus musculus, mouse colon carcinoma ATCC 5x105 Fetal bovine serum (FBS; 16000-044, Thermofisher Scientific, USA), penicillin-streptomycin (10,000 units / ml of penicillin and 10,000 qg / ml of streptomycin; 15140122, Thermofisher Scientific, USA) and RPMU640 (A1049101, Thermofisher Scientific, USA) were mixed to have the composition described in Table 6 below per 100 ml and were used as a culture medium for carcinoma cells. [Table 6] Composition Volume Final Concentration Product Manufacturer Cat.# Culture medium for cancer cells. FBS Thermofish er scientific 16000-044 10 ml 10% Penicillin & Streptomycin Thermofish er scientific 15140122 1 ml 10,000 U / ml penicillin & 10,000 µg / ml streptomycin RPMI 1640 Thermofish er scientific A1049101 Per 100 ml Example of preparation 6. Preparation of the mouse model with carcinoma Example Preparation 6.1. Quarantine and Acclimation Processes for Experimental Mice 36 twelve-week-old female BALB / c mice were purchased from ORIENT BIO Inc. The mice were taken to the animal laboratory and acclimated for five days before being used in the experiment. Upon arrival, each mouse was assessed for its appearance and weighed to determine its body weight. General symptoms were observed once daily during the five-day acclimation period, and body weight was measured at the end of the acclimation period. General symptoms and changes in body weight were then checked to assess the mice's health status. Mice exhibiting abnormalities were euthanized under CO2 anesthesia. Information on laboratory mice is summarized and shown in Table 7 below. [Table 7] Strain of origin Purchased Age Gender Mouse Balb / c OrientBio 12 weeks old female CAzann / zznz / E / YiAi Example of preparation 6.2. Carcinoma cell line transplantation For a tumor growth inhibition model, body weight was measured the day after the end of the quarantine and acclimation period. Then, a CT26 cell suspension (5 x 10⁵ cells / 0.1 ml) prepared for healthy animals was dispensed, filled into a disposable syringe, and administered subcutaneously (0.1 ml / head) in the right side of the back of the mouse for transplantation. General symptoms were observed once daily during the engraftment and growth period following cell line transplantation. Example of preparation 6.3. Grouping of mouse models of tumor growth inhibition After a certain period of CT26 cell transplantation, the tumor volume and body weight of mice without an abnormal health status were measured, and they were divided into 4 groups (9 mice per group) so that the average of each group reached 50 mm3. IV. Determination of the anticancer activity of the NK cell and the fusion protein dimer: In vitro Example 1. Determination of the inhibitory effect of NK cells and / or fusion protein dimer on cancer cell growth against various carcinomas Referring to a plate design for use in a 96-well plate, 50 µL of 0.01% poly-L-ornithine solution (Cat# P4957) (Sigma Aldrich, USA) were dispensed into each well and covered. The wells were then incubated at room temperature for 1 hour. After 1 hour, the dispensed 0.01% poly-L-ornithine solution was removed and allowed to dry completely at room temperature for 1 hour. Two µL of Deep Red CELLTRACKER™ dye (Cat# C34565) (Thermo Scientific, Waltham, MA, USA) were added to the prepared cancer cells (target cells) at a density of 4 x 10⁵ cells / ml and allowed to react for 60 minutes under conditions of 37 °C and 5% CO₂. After the reaction, the resulting sample was centrifuged at 300 x g for 5 minutes. The supernatant was discarded and then diluted in RPMU640 + 5% hABS culture solution to a density of 4 x 10⁵ cells / ml. 50 µL of the prepared cancer cells were dispensed into one well of a coated 96-well plate. The prepared plate was then placed in an INCUCYTE® Live-Cell Analysis system (Satorius, Germany) and allowed to stabilize for 30 minutes. A culture solution containing test material was prepared in RPMI1640 + 5% hABS according to Table 8 below. [Table 8] CRzann / zznz / E / YiAi Control test substance GI-101 CD80-Fc+Fc-IL2v2 Concentration 0 nM 100 nM CD80-Fc: 100 nM, Fc-IL2v2: 100 nM Natural killer cells (effector cells) were prepared by suspension in an RPMI1640 + 5% hABS culture solution at 4 x 10⁵ cells / ml. With reference to Table 9 below, the natural killer cells prepared in Preparation Examples 1 and 2 were added to each well in the dispensed cancer cell plate, and then 100 μL of INCUCYTE® CytoTox (250 nM)-treated culture solution was added. [Table 9] E / T ratio 0 / 1 1 / 3 1 / 1 3 / 1 10 / 1 Number of NK cells - 6.7X103 2x104 6x104 2x105 Number of cancer cells 2x104 2x104 2x104 2x104 2x104 Then, it was placed in the INCUCYTE® live cell analysis system and analyzed for 3 days with a time interval of 30 minutes. Example 1.1. Determination of the effectiveness of the fusion protein dimer only in the presence of a target cancer cell without an NK cell As described in Example 1 above, the respective test materials GI101 and CD80-Fc+Fc-IL2v2 were observed to not significantly affect the viability of cancer cells when culturing cell lines for various cancer types (K562, MDA-MB-231, HCT-116 and A549 cell lines) in the presence of target cancer cells alone without NK cells (see Table 9, E / T ratio = 0 / 1) (Figures 8 to 11). Example 1.2. Proliferative inhibition effect of NK cells and fusion protein dimer on K562 cells (lymphoblasts) The ability of natural killer cells to kill cancer cells was confirmed in a K562 cell line, a leukemia cancer cell line. Specifically, the viability of cancer cells was confirmed following treatment with either GL101 or CD80-Fc+Fc-IL2v2 test material as a combination when K562 cell lines were co-cultured as target cells (T) and natural killer cells as effector cells (E) with E / T ratios of 1 / 3, 1 / 1, 3 / 1, and 10 / 1, respectively. The results showed that by killing K562 cancer cells, treatment with GI-101 as a natural killer cell composite material, which is a form of the IL2-FcCD80 fusion protein, inhibited cancer cell viability more than treatment with CD80-Fc+Fc-IL2v2 (Figures 16 to 19). Example 1.3. Proliferative inhibition effect of NK cell and fusion protein dimer on cancer cells against MDA-MB231 The ability of natural killer cells to kill cancer cells was confirmed in an MDA-MB231 cell line, a breast cancer cell line. Specifically, the viability of cancer cells was confirmed following treatment with either GI-101 or CD80-Fc+Fc-IL2v2 test material when MDAMB231 cell lines were co-cultured as target cells (T) and natural killer cells as effector cells (E) at E / T ratios of 1 / 3, 1 / 1, 3 / 1, and 10 / 1, respectively. The results showed that by killing MDA-MB231 cancer cells, treatment with GI-101 as a natural killer cell composite material, which is a form of the IL2-Fc-CD80 fusion protein, inhibited the viability of cancer cells more than treatment with CD80-Fc+FcIL2v2 (Figures 16 to 19). Example 1.4. Proliferative inhibition effect of NK cell and fusion protein dimer on HCT-116 cancer cells The ability of natural killer cells to kill cancer cells was confirmed in an HCT-116 cell line, a colon cancer cell line. Specifically, the viability of cancer cells was confirmed following treatment with either GI-101 or CD80-Fc+Fc-IL2v2 test material when HCT-116 cell lines were co-cultured as target cells (T) and natural killer cells as effector cells (E) at E / T ratios of 1 / 3, 1 / 1, 3 / 1, and 10 / 1, respectively. The results showed that by killing HCT-116 cancer cells, treatment with GI-101 as a natural killer cell composite material, which is a form of the IL2-FcCD80 fusion protein, inhibited cancer cell viability more than treatment with CD80-Fc+Fc-IL2v2 (Figures 20 to 23). Example 1.5. Proliferative inhibition effect of NK cell and fusion protein dimer against A549 cell The ability of natural killer cells to kill cancer cells was confirmed in an A549 cell line, a colon cancer cell line. Specifically, the viability of cancer cells was confirmed following treatment with either GI-101 or CD80-Fc+FcIL2v2 test material as a combined material when A549 cell lines were co-cultured as target cells (T) and natural killer cells as effector cells (E) at E / T ratios of 1 / 3, 1 / 1, 3 / 1, and 10 / 1, respectively. The results showed that by killing A549 cancer cells, treatment with GI-101 as a natural killer cell composite material, which is a form of the IL2-FcCD80 fusion protein, inhibited the viability of cancer cells more than treatment with CD80-Fc+Fc-IL2v2 (Figures 24 to 27). V. Determination of the cancer-killing capacity of NK cells and fusion protein dimer in a mouse model of carcinoma: In vivo Example 2. Administration of mGI-101 and NK cell In a mouse model of carcinoma, the mGI-101 obtained in Preparation 4 was administered intraperitoneally, and the mouse-derived NK cells prepared in Preparation 3 were administered intravenously. Administration was performed a total of three times on the day of administration (day 6, day 10, and day 13 post-tumor transplantation) using a disposable syringe (31G, 1 ml). For a tumor growth inhibition model, as shown in Table 10 below, the cells administered and the administration doses for the four groups were different (Figure 28). CAzann / zznz / E / YiAi [Table 10] Group Administered cells Dose of hIgG4 or mGI-101 (mg / kg) Number of NK cells G1 (control) hIgG4 4 0 G2 h!gG4 + NK cell 4 IxlO6 G3 mGHOl alone 0.6 0 G4 mGIlOl + NK cell 0.6 1X106 Example 3. Measurement of tumor volume in the mouse model of carcinoma The maximum length (L) and perpendicular width (W) of the tumor were measured twice weekly using a Digital Caliper (mitutoyo, Japan) and applied to Equation 1 below to calculate the tumor volume (TV). [Equation 1] TV (mm) = WXWXLX 0.5 The percentage of tumor growth inhibition was calculated using the following Equation 2: [Equation 2] Inhibition of tumor growth (%) = (l-(Ti-T0) / (Vi-V0))xl00 Ti = tumor volume before administration in the test group TO = tumor volume after administration in the test group Vi = tumor volume before administration in the control group V0 = tumor volume after administration in the control group The tumor volume of each individual before administration was set as the value measured at the time of pooling. Example 4. Determination of the inhibitory effect on tumor growth in the CT26 transplant mouse model of carcinoma Example 4.1. Tumor volume measurements CT26 colorectal cancer cell suspension (5 x 10⁵ cells / 0.1 mL) prepared for healthy Balb / c mice was dispensed, and the prepared solution was loaded into a disposable syringe and administered subcutaneously (0.1 mL / head) in the right flank of the transplant recipient. After tumor transplantation, the drugs listed in Table 10 were administered. Tumor size was then measured on days 10, 13, and 17. Tumor growth was inhibited in the groups treated with natural killer (NK) cells or mGLIOl alone compared to the control (vehicle) group. Tumor growth was also inhibited in the groups treated with natural killer (NK) cells in combination with mGLIOl compared to the control (vehicle) group.Tumor growth was inhibited in the group treated with natural killer cells in combination with mGI-101 compared to the groups treated with natural killer cells or mGI-101 alone (Figure 29). Example 4.2. Tumor growth inhibition test The tumor growth inhibition rate was calculated at the end of the experiment (after tumor transplantation, day 17) compared to the drug treatment on day 1 (after tumor transplantation, day 10). The control (vehicle) group consisted of 3 mice with a tumor growth inhibition rate of 30% or more, 3 mice with a tumor growth inhibition rate of 50% or more, and 2 mice with a tumor growth inhibition rate of 80%. The natural killer cell treatment group consisted of 6 mice with a tumor growth inhibition rate of 34% or more. CAzann / zznz / E / YiAi tumor growth inhibition of 30% or more, 5 mice with a tumor growth inhibition rate of 50% or more, and 2 mice with a tumor growth inhibition rate of 80%. The mGI-101 treatment group had 5 mice with a tumor growth inhibition rate of 30% or more, 5 mice with a tumor growth inhibition rate of 50% or more, and 1 mouse with a tumor growth inhibition rate of 80%. The natural killer cell and mGI-101 combination treatment group had 7 mice with a tumor growth inhibition rate of 30% or more, 6 mice with a tumor growth inhibition rate of 50% or more, and 3 mice with a tumor growth inhibition rate of 80% (Figure 30).In Figure 30, a black bar indicates a tumor growth inhibition rate of 30% or more, a light gray bar indicates a tumor growth inhibition rate of 50% or more, and a dark gray bar indicates a tumor growth inhibition rate of 80% or more. Example 4.3. Measurement of tumor volume for individual laboratory animals Tumor growth was determined in individual laboratory animals in each treatment group. Specifically, tumor size was determined in individual laboratory animals in the control (vehicle) group, in the natural killer (NK) cell, mGI-101, and natural killer cell + mGI-101 treatment groups, and is shown in Figure 31. In Figure 31, a dotted line indicates a tumor size of 500 mm³ and a solid line indicates a tumor size of 250 mm³. More specifically, the degree of tumor growth in individual laboratory animals in the control group was determined and is shown in Figure 32, and the degree of tumor growth in individual laboratory animals in the natural killer cell treatment group was determined and is shown in Figure 33. Additionally, the degree of tumor growth in individual laboratory animals in the mGI-101 treatment group was determined and is shown in Figure 34, and the degree of tumor growth in individual laboratory animals in the natural killer cell and mGI-101 treatment group was determined and is shown in Figure 35.

Claims

1. A pharmaceutical composition for use in cancer treatment in combination with a natural killer cell comprising, as an active ingredient, a fusion protein comprising an IL-2 protein and a CD80 protein 2. The pharmaceutical composition according to claim 1, wherein the IL-2 protein and the CD80 protein are linked by means of a linker.

3. The pharmaceutical composition according to claim 1, wherein the IL-2 protein has the amino acid sequence of SEQ ID NO:

10.

4. The pharmaceutical composition according to claim 1, wherein the IL-2 protein is a variant of IL-2.

5. The pharmaceutical composition according to claim 4, wherein the IL2 variant is obtained by substitution of at least one of the 38°, 42°, 45°, 61° and 72° amino acids in the amino acid sequence of SEQ ID NO:

10.

6. The pharmaceutical composition according to claim 4, wherein the IL2 variant is obtained by at least one substitution selected from the group consisting of R38A, F42A, Y45A, E61R and L72G, in the amino acid sequence of SEQ ID NO:

10.

7. The pharmaceutical composition according to claim 4, wherein the variant of 1L2 comprises any one selected from the following substitution combinations (a) to (d) in the amino acid sequence of SEQ ID NO: 10: (a) R38A / F42A (b) R38A / F42A / Y45A (c) R38A / F42A / E61R (d) R38A / F42A / L72G.

8. The pharmaceutical composition according to claim 4, wherein the IL2 variant has the amino acid sequence SEQ ID NO: 6, 22, 23 or 24. CAzann / zznz / E / YiAi 9. The pharmaceutical composition according to claim 1, wherein the CD80 protein has the amino acid sequence of SEQ ID NO:

11.

10. The pharmaceutical composition according to claim 1, wherein the CD80 protein is a fragment of CD80.

11. The pharmaceutical composition according to claim 10, wherein the CD80 fragment consists of the 35° to 242° amino acids in SEQ ID NO:

11.

12. The pharmaceutical composition according to claim 2, wherein the linker is an albumin or an Fe domain of an immunoglobulin.

13. The pharmaceutical composition according to claim 12, wherein the Fe domain is a wild-type Fe domain or a variant of the Fe domain.

14. The pharmaceutical composition according to claim 12, wherein the Fe domain has the amino acid sequence of SEQ ID NO:

4.

15. The pharmaceutical composition according to claim 13, wherein the Fe domain variant has the amino acid sequence of SEQ ID NO:

12.

16. The pharmaceutical composition according to claim 1, wherein the fusion protein consists of the following structural formula (I) or (II): N'-X-[linker (l)]n-domain Fc-[linker (2)]mYC (I) N'-Y-[linker (l)]n-domain Fc-[linker (2)]mXC (II) wherein, in structural formulas (I) and (II), N' is the N-terminus of the fusion protein, C is the C-terminus of the fusion protein, X is a CD80 protein, Y is an IL-2 protein, linkers (1) and (2) are peptide linkers, and CAzann / zznz / E / YiAi nym are each independently 0 or 1.

17. The pharmaceutical composition according to claim 16, wherein the linker (1) is a peptide linker consisting of the amino acid sequence of SEQ ID NO:

3.

18. The pharmaceutical composition according to claim 16, wherein the linker (2) is a peptide linker consisting of the amino acid sequence of SEQ ID NO:

5.

19. The pharmaceutical composition according to claim 16, wherein the fusion protein consists of the structural formula (I).

20. The pharmaceutical composition according to claim 1, wherein the fusion protein has a sequence identity of 85% or more with the amino acid sequence of SEQ ID NO: 9, 26, 28 or 30.

21. The pharmaceutical composition according to claim 1, wherein the fusion protein is a dimer.

22. The pharmaceutical composition according to claim 1, wherein cancer is any cancer selected from the group consisting of gastric cancer, liver cancer, lung cancer, colorectal cancer, breast cancer, prostate cancer, ovarian cancer, pancreatic cancer, cervical cancer, thyroid cancer, laryngeal cancer, acute lymphoblastic leukemia, brain tumor, neuroblastoma, retinoblastoma, head and neck cancer, salivary gland cancer, and lymphoma.