Cell therapy

Abstract

The present disclosure provides a novel modality for a new target disease (e.g. pancreatic cancer). The present disclosure applies a mRNA CAR-T vaccine to CAR-T for a new target disease (e.g., pancreatic cancer). In the present disclosure, it has been revealed, by in vitro and in vivo experiments, that a mRNA CAR-T vaccine that targets FAP as an antigen can achieve a potent anti-tumor effect in in vivo editing. As for a mechanism for inhibiting the effect of a mRNA CAR-T vaccine, the pathways involving regulatory T cells and the like have also been revealed. As for a synergistic effect with an immune checkpoint agonist, a "condition" for achieving a potent anti-tumor effect in vivo has also been revealed through much trial and error.

Description

cell therapy

[0001] The present disclosure relates to breakthrough cell therapies.

[0002] The cancer stromal fibrosis caused by activated fibroblasts (CAFs) in pancreatic cancer reduces the effectiveness of chemotherapy, radiation therapy, and immunotherapy before and after surgery. Controlling this reaction is important for overcoming intractable cancers. In this study, we aimed to apply chimeric receptor T (CAR-T) "designer cell" therapy, which has been dramatically effective in hematopoietic tumors, to solid cancers for the first time by applying RNA vaccine technology, paving the way for optimizing efficacy and safety.

[0003] The present disclosure applies mRNA CAR-T vaccines to CAR-T for new target diseases (e.g., pancreatic cancer). In vitro and in vivo experiments have demonstrated that mRNA CAR-T vaccines using FAP as an antigen exert a strong antitumor effect through in vivo editing. Pathways such as regulatory T cells have been identified as a mechanism for inhibiting the effects of mRNA CAR-T vaccines. Through trial and error, the "conditions" for exerting a strong antitumor effect in vivo as a synergistic effect with immune checkpoint agonists have been clarified. The present disclosure provides, for example, the following:

[0004] (Item 1) A composition for treating or preventing cancer, comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for FAP (fibroblast-activation protein); and B) optionally, a lipid nanoparticle (LNP). (Item 2) The composition according to any one of the above items, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item 3) The composition according to any one of the above items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item 4) The composition according to any one of the above items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item 5) The composition of any one of the preceding items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item 6) The composition of any one of the preceding items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item 7) The composition of any one of the preceding items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item 8) The composition of any one of the preceding items, wherein the CAR is encoded by the nucleic acid sequence set forth in SEQ ID NO: 1 or 3, or a modified sequence thereof, or comprises the amino acid sequence set forth in SEQ ID NO: 2 or 4, or a modified sequence thereof. (Item 9) The composition of any one of the preceding items, wherein the nucleic acid sequence encoding the CAR comprises the nucleic acid sequence set forth in SEQ ID NO: 1, or a modified sequence thereof, or a sequence encoding the nucleic acid sequence set forth in SEQ ID NO: 2, or a modified sequence thereof. (Item 10) The composition according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP. (Item 11) The composition according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137).(Item 12) The composition according to any one of the above items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, FAP scFv, CD8a hinge, CD8a transmembrane region, and 4-1BB cytoplasmic domain. (Item 13) The composition according to any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)). (Item 14) The composition according to any one of the above items, wherein the cancer is a solid cancer. (Item 15) The composition according to any one of the above items, wherein the composition is delivered to FAP. (Item 16) The composition according to any one of the above items, wherein the composition is for inducing T cells in a subject. (Item 17) The composition according to any one of the above items, wherein the composition is used in combination with another anticancer agent. (Item 18) The composition according to any one of the above items, wherein the other anticancer agent is for a solid cancer. (Item 19) The composition of any one of the above items, wherein the other anticancer agent is one known to be effective against the cancer afflicting the subject. (Item 20) The composition of any one of the above items, wherein the composition is used in combination with an anticancer agent (such as 5-FU), an immune checkpoint agonist (such as a PD-1 antibody, a PD-L1 antibody, or a CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item 21) The composition of any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item 22) The composition of any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item 23) The composition according to any one of the above items, wherein the composition is used in combination with at least one selected from the group consisting of those that target tumor cells themselves, those that target stromal cells, and those that regulate immunity.(Item 24) The composition according to any one of the above items, wherein the substance targeting tumor cells themselves comprises at least one selected from the group consisting of chemotherapeutic agents (low molecular weight compound anticancer drugs), molecular targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid pharmaceuticals, microRNA, aptamers, cross-linked DNA, etc. (Item 25) The composition according to any one of the above items, wherein the substance targeting stromal cells comprises at least one selected from the group consisting of anti-FGF antibodies of FGFR against fibroblasts, anti-PDGF bodies, inhibitors thereof, small molecules, etc. (Item 26) The composition according to any one of the preceding items, wherein the substance that regulates immunity comprises at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals of regulatory T cells (e.g., IL2) (anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item 27) The composition according to any one of the above items, wherein if the cancer is a digestive cancer, including colon cancer and pancreatic cancer, or breast cancer, the other anticancer drug is 5FU; if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP; and if the cancer is a pathological condition in which DNA synthesis is dominant, the other anticancer drug is used in combination with a drug that acts on the regulation of nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from adduct CDDP, the antimetabolite methotrexate, 5FU, etc. (Item 28) The composition according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one of an agent that regulates amino acids (particularly methionine, tryptophan, etc.), a lipid regulator, or a carbohydrate regulator (for carbohydrates, a glucose transporter).(Item 29) A pharmaceutical kit or combination comprising: 1) an agent comprising A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for FAP, and B) optionally lipid nanoparticles (LNPs), and 2) another anticancer agent different from 1). (Item 30) A pharmaceutical kit or combination according to the above items, characterized in that it is used to treat or prevent cancer. (Item 31) A pharmaceutical kit or combination according to any one of the above items, further comprising the features of any one or more of items 1 to 28. (Item 32) A composition according to any one of the above items, or a pharmaceutical kit or combination according to any one of the above items, characterized in that the mRNA is administered by intravenous injection. (Item A1) A pharmaceutical kit or combination according to the above items, characterized in that A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for FAP (fibroblast-activation protein), and B) optionally combined with lipid nanoparticles (LNPs), for treating or preventing cancer. (Item A2) The mRNA according to any one of the preceding items, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item A3) The mRNA according to any one of the preceding items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item A4) The mRNA according to any one of the preceding items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item A5) The mRNA according to any one of the preceding items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item A6) The mRNA according to any one of the preceding items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item A7) The mRNA according to any one of the preceding items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol.(Item A8) The mRNA according to any one of the preceding items, wherein the CAR is encoded by the nucleic acid sequence of SEQ ID NO: 1 or 3 or a modified sequence thereof, or comprises the amino acid sequence of SEQ ID NO: 2 or 4 or a modified sequence thereof. (Item A9) The mRNA according to any one of the preceding items, wherein the nucleic acid sequence encoding the CAR comprises the nucleic acid sequence of SEQ ID NO: 1 or a modified sequence thereof, or a sequence encoding the nucleic acid sequence of SEQ ID NO: 2 or a modified sequence thereof. (Item A10) The mRNA according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP. (Item A11) The mRNA according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item A12) The mRNA according to any one of the above items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, FAP scFv, CD8a hinge, CD8a transmembrane region, and 4-1BB cytoplasmic domain. (Item A13) The mRNA according to any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)). (Item A14) The mRNA according to any one of the above items, wherein the cancer is a solid cancer. (Item A15) The mRNA according to any one of the above items, wherein the composition is delivered to FAP. (Item A16) The mRNA according to any one of the above items, wherein the composition is for inducing T cells in a subject. (Item A17) The mRNA according to any one of the above items, wherein the composition is used in combination with another anticancer drug. (Item A18) The mRNA according to any one of the above items, wherein the other anticancer drug is an anticancer drug for a solid cancer. (Item A19) The mRNA according to any one of the above items, wherein the other anticancer drug is an anticancer drug known to be effective against the cancer afflicting the subject.(Item A20) The mRNA according to any one of the above items, wherein the composition is used in combination with an anticancer drug (such as 5-FU), an immune checkpoint agonist (such as a PD-1 antibody, a PD-L1 antibody, or a CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item A21) The mRNA according to any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item A22) The mRNA according to any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item A23) The composition according to any one of the above items, wherein the composition is used in combination with at least one selected from the group consisting of compositions that target tumor cells themselves, compositions that target stromal cells, and compositions that regulate immunity. (Item A24) The mRNA according to any one of the above items, wherein the substance targeting tumor cells themselves includes at least one selected from the group consisting of a chemotherapeutic agent, a molecular targeted drug (anti-HER2 antibody, anti-EGFR antibody, anti-TGFb antibody, or an inhibitor thereof, small molecule, etc.), or an antibody or inhibitor targeting at least one of these, either singly or in combination, radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid pharmaceuticals, microRNA, aptamers, cross-linked DNA, etc. (Item A25) The mRNA according to any one of the above items, wherein the substance targeting stromal cells includes at least one selected from the group consisting of an anti-FGF antibody against FGFR for fibroblasts, an anti-PDGF antibody, an inhibitor thereof, small molecule, etc.(Item A26) The mRNA according to any one of the preceding items, wherein the substance that regulates immunity includes at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals of regulatory T cells (e.g., IL2) (e.g., anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item A27) The mRNA according to any one of the above items, wherein if the cancer is a digestive cancer including colon cancer and pancreatic cancer, or breast cancer, the other anticancer drug is 5FU, if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP, and if the cancer is a pathological condition in which DNA synthesis is dominantly active, the other anticancer drug is used in combination with a drug that acts on nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from the group consisting of adduct CDDP, the antimetabolite methotrexate, and 5FU. (Item A28) The mRNA according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one of an agent that controls amino acids (particularly methionine, tryptophan, etc.), an agent that controls lipids, and an agent that controls carbohydrates (for carbohydrates, a glucose transporter). (Item A29) The mRNA according to any one of the preceding items, further combined with an anticancer drug different from the mRNA or a drug containing the same. (Item A30) The mRNA according to any one of the preceding items, characterized in that the mRNA is administered by intravenous injection. (Item B1) Use of A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for fibroblast-activation protein (FAP), optionally combined with B) lipid nanoparticles (LNPs), for the manufacture of a medicament for treating or preventing cancer.(Item B2) The use according to the above items, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item B3) The use according to any one of the above items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item B4) The use according to any one of the above items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item B5) The use according to any one of the above items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item B6) The use according to any one of the above items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item B7) The use according to any one of the above items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item B8) The use according to any one of the above items, wherein the CAR is encoded by the nucleic acid sequence set forth in SEQ ID NO: 1 or 3, or a modified sequence thereof, or comprises the amino acid sequence set forth in SEQ ID NO: 2 or 4, or a modified sequence thereof. (Item B9) The use according to any one of the above items, wherein the nucleic acid sequence encoding the CAR comprises the nucleic acid sequence set forth in SEQ ID NO: 1, or a modified sequence thereof, or a sequence encoding the nucleic acid sequence set forth in SEQ ID NO: 2, or a modified sequence thereof. (Item B10) The use according to any one of the above items, wherein the CAR comprises an extracellular domain portion for FAP. (Item B11) The use according to any one of the above items, wherein the CAR comprises an extracellular domain portion for FAP and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item B12) The use according to any one of the preceding items, wherein the CAR comprises at least one selected from the group consisting of a CD8 leader sequence, a FAP scFv, a CD8a hinge, a CD8a transmembrane region, and a 4-1BB cytoplasmic domain.(Item B13) The use according to any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)). (Item B14) The use according to any one of the above items, wherein the cancer is a solid cancer. (Item B15) The use according to any one of the above items, wherein the composition is delivered to FAP. (Item B16) The use according to any one of the above items, wherein the composition is for inducing T cells in a subject. (Item B17) The use according to any one of the above items, wherein the composition is used in combination with another anticancer agent. (Item B18) The use according to any one of the above items, wherein the other anticancer agent is directed against a solid cancer. (Item B19) The use according to any one of the above items, wherein the other anticancer agent is one known to be effective against the cancer from which the subject is afflicted. (Item B20) The use according to any one of the above items, wherein the composition is used in combination with an anticancer agent (such as 5-FU), an immune checkpoint agonist (such as PD-1 antibody, PD-L1 antibody, or CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item B21) The use according to any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item B22) The use according to any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item B23) The composition according to any one of the above items, wherein the composition is used in combination with at least one selected from the group consisting of compositions that target tumor cells themselves, compositions that target stromal cells, and compositions that regulate immunity.(Item B24) The use according to any one of the above items, wherein the substance targeting tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents, molecular targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid pharmaceuticals, microRNA, aptamers, cross-linked DNA, etc. (Item B25) The use according to any one of the above items, wherein the substance targeting stromal cells includes at least one selected from the group consisting of anti-FGF antibodies of FGFR against fibroblasts, anti-PDGF antibodies, inhibitors thereof, small molecules, etc. (Item B26) The use according to any one of the above items, wherein the substance that regulates immunity includes at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals of regulatory T cells (e.g., IL2) (anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item B27) The use according to any one of the above items, wherein if the cancer is a digestive cancer, including colon cancer and pancreatic cancer, or breast cancer, the other anticancer drug is 5FU, if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP, and if the cancer is a pathological condition in which DNA synthesis is dominant, the other anticancer drug is used in combination with a drug that acts on the regulation of nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from adduct CDDP, the antimetabolite methotrexate, 5FU, etc. (Item B28) The use according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one of an agent that regulates amino acids (particularly methionine, tryptophan, etc.), an agent that regulates lipids, or an agent that regulates carbohydrates (for carbohydrates, a glucose transporter).(Item B29) Use of a pharmaceutical kit or combination of A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for FAP, optionally combined with B) lipid nanoparticles (LNPs), for the manufacture of a medicine, the kit or combination comprising an anticancer drug different from the mRNA. (Item B30) The use according to the above items, characterized in that it is for treating or preventing cancer. (Item B31) The use according to any one of the above items, further comprising the features of any one or more of items 1 to 28. (Item B32) The use according to any one of the above items, characterized in that the mRNA is administered by intravenous injection. (Item C1) A method for treating or preventing cancer in a subject, comprising the step of administering to a subject A) an effective amount of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for FAP (fibroblast-activation protein), and B) optionally an effective amount of lipid nanoparticles (LNPs). (Item C2) The method according to any one of the preceding items, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item C3) The method according to any one of the preceding items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item C4) The method according to any one of the preceding items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item C5) The method according to any one of the preceding items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item C6) The method according to any one of the preceding items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item C7) The method according to any one of the preceding items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol.(Item C8) The method of any one of the above items, wherein the CAR is encoded by the nucleic acid sequence of SEQ ID NO: 1 or 3, or a modified sequence thereof, or comprises the amino acid sequence of SEQ ID NO: 2 or 4, or a modified sequence thereof. (Item C9) The method of any one of the above items, wherein the nucleic acid sequence encoding the CAR comprises the nucleic acid sequence of SEQ ID NO: 1, or a modified sequence thereof, or a sequence encoding the nucleic acid sequence of SEQ ID NO: 2, or a modified sequence thereof. (Item C10) The method of any one of the above items, wherein the CAR comprises an extracellular domain portion for FAP. (Item C11) The method of any one of the above items, wherein the CAR comprises an extracellular domain portion for FAP and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item C12) The method of any one of the above items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, FAP scFv, CD8a hinge, CD8a transmembrane region, and 4-1BB cytoplasmic domain. (Item C13) The method of any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)). (Item C14) The method of any one of the above items, wherein the cancer is a solid cancer. (Item C15) The method of any one of the above items, wherein the composition is delivered to FAP. (Item C16) The method of any one of the above items, wherein the composition is for inducing T cells in a subject. (Item C17) The method of any one of the above items, wherein the composition is used in combination with another anticancer drug. (Item C18) The method of any one of the above items, wherein the other anticancer drug is for a solid cancer. (Item C19) The method according to any one of the preceding items, wherein the other anticancer drug is known to be effective against the cancer from which the subject suffers.(Item C20) The method according to any one of the preceding items, wherein the composition is used in combination with an anticancer drug (such as 5-FU), an immune checkpoint agonist (such as a PD-1 antibody, a PD-L1 antibody, or a CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item C21) The method according to any one of the preceding items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item C22) The method according to any one of the preceding items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item C23) The composition according to any one of the preceding items, wherein the composition is used in combination with at least one selected from the group consisting of compositions that target tumor cells themselves, compositions that target stromal cells, and compositions that regulate immunity. (Item C24) The method according to any one of the above items, wherein the substance targeting the tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents, molecular targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid pharmaceuticals, microRNA, aptamers, cross-linked DNA, etc. (Item C25) The method according to any one of the above items, wherein the substance targeting the stromal cells includes at least one selected from the group consisting of anti-FGF antibodies of FGFR against fibroblasts, anti-PDGF antibodies, inhibitors thereof, small molecules, etc. (Item C26) The method according to any one of the preceding items, wherein the substance that controls immunity includes at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals (such as IL2) of regulatory T cells (anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.).(Item C27) The method according to any one of the above items, wherein if the cancer is a digestive cancer, including colon cancer and pancreatic cancer, or breast cancer, the other anticancer drug is 5FU, if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP, and if the cancer is a pathological condition in which DNA synthesis is dominantly affected, the other anticancer drug is used in combination with a drug that acts on the regulation of nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from adduct CDDP, the antimetabolite methotrexate, 5FU, etc. (Item C28) The method according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one of an agent that regulates amino acids (particularly methionine, tryptophan, etc.), an agent that regulates lipids, or an agent that regulates carbohydrates (for carbohydrates, a glucose transporter). (Item C29) A method for treating or preventing cancer in a subject, comprising the steps of: 1) administering to the subject an effective amount of an agent comprising A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for FAP, and B) optionally lipid nanoparticles (LNPs), and 2) an effective amount of an anticancer agent different from 1). (Item C30) The method of any one of the above items, further comprising the features of any one or more of items 1 to 28. (Item C31) The method of any one of the above items, characterized in that the mRNA is administered intravenously.

[0005] <Aspects utilizing a cancer stem cell (CSC) marker, a cancer stem cell-like cell (CSCLC) marker, and / or an ES cell-associated marker> (Item X1) A composition for treating or preventing cancer, comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for a cancer stem cell (CSC) marker, a cancer stem cell-like cell (CSCLC) marker, and / or an ES cell-associated marker; and B) optionally, a lipid nanoparticle (LNP). (Item X1A) The composition according to any one of the above items, wherein the cancer stem cell (CSC) marker, a cancer stem cell-like cell (CSCLC) marker, and / or an ES cell-associated marker is a cancer stem cell (CSC) marker. (Item X1B) The composition according to any one of the above items, wherein the cancer stem cell (CSC) marker, a cancer stem cell-like cell (CSCLC) marker, and / or an ES cell-associated marker is a cancer stem cell (CSCLC) marker. (Item X1C) The composition according to any one of the above items, wherein the cancer stem cell (CSC) marker, cancer stem cell-like cell (CSCLC) marker, and / or ES cell-associated marker is an ES cell-associated marker. (Item X2) The composition according to any one of the above items, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item X3) The composition according to any one of the above items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item X4) The composition according to any one of the above items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item X5) The composition according to any one of the preceding items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item X6) The composition according to any one of the preceding items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).(Item X7) The composition according to any one of the above items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item X8) The CSC markers are CD133 (PROM1), LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5), EpCAM (Epithelial Cell Adhesion Molecule), CD13 / APN, CD24, ALDH (ALDH1A1), and CD34. ＋ / CD38 －, CD123 (IL-3 receptor α), CD44v, CD90 (Thy-1), and those described in List Z. Alternatively, these are not limited to these, but are merely examples, and include markers used for identifying and targeting the CSC markers. (Item X8A) The composition of any one of the above items, wherein the CSCLC marker is selected from the group consisting of CD133, EGFR / Her2 / neu, CD24, Claudin18.2, Claudin6, FGFR, NRP, c-Met, CD13 / APN, EpCAM, LGR5, CD44v, CD24, and those described in List Z. Alternatively, these are not limited to these, but are merely examples, and include markers used for identifying and targeting the CSCLC markers. (Item X8B) The composition of any one of the above items, wherein the ES cell-associated marker is selected from the group consisting of OCT, SOX, and those described in List Z. (Item X9) The composition of any one of the above items, wherein the CAR is encoded by the nucleic acid sequence set forth in SEQ ID NO: 22, 24, 26, 28, 30, 32, 34, or 36, or a modified sequence thereof, or comprises the amino acid sequence set forth in SEQ ID NO: 23, 25, 27, 29, 31, 33, 35, or 37, or a modified version thereof. (Item X10) The composition of any one of the above items, wherein the CAR comprises an extracellular domain portion of the cancer stem cell (CSC), cancer stem cell-like cell (CSCLC) marker and / or ES cell-associated marker. (Item X11) The composition according to any one of the above items, wherein the CAR comprises an extracellular domain portion for the cancer stem cell (CSC), cancer stem-like cell (CSCLC) marker and / or ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item X12) The composition according to any one of the above items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, FAP scFv, CD8a hinge, CD8a transmembrane region, and 4-1BB cytoplasmic domain.(Item X13) The composition of any one of the above items, wherein the cancer is a cancer whose treatment is promoted by treating cancer stem cells. (Item X14) The composition of any one of the above items, wherein the cancer is a solid cancer. (Item X15) The composition of any one of the above items, wherein the composition is delivered to cancer stem cells. (Item X16) The composition of any one of the above items, wherein the composition is for inducing T cells in a subject. (Item X17) The composition of any one of the above items, wherein the composition is used in combination with another anticancer drug. (Item X18) The composition of any one of the above items, wherein the other anticancer drug is directed against a solid cancer. (Item X19) The composition of any one of the above items, wherein the other anticancer drug is one known to be effective against the cancer afflicting the subject. (Item X20) The composition according to any one of the above items, wherein the composition is used in combination with an anticancer agent (such as 5-FU), an immune checkpoint agonist (such as a PD-1 antibody, a PD-L1 antibody, or a CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item X21) The composition according to any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item X22) The composition according to any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item X23) The composition according to any one of the above items, wherein the composition is used in combination with at least one selected from the group consisting of compositions that target tumor cells themselves, compositions that target stromal cells, and compositions that regulate immunity.(Item X24) The composition according to any one of the above items, wherein the substance targeting tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (low-molecular-weight compound anticancer drugs), molecularly targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid drugs, microRNA, aptamers, cross-linked DNA, etc. (Item X25) The composition according to any one of the above items, wherein the substance targeting stromal cells includes at least one selected from the group consisting of anti-FGF antibodies against FGFR for fibroblasts, anti-PDGF bodies, inhibitors thereof, small molecules, etc. (Item X26) The composition according to any one of the preceding items, wherein the substance that regulates immunity includes at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals of regulatory T cells (e.g., IL2) (anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item X27) The composition according to any one of the above items, wherein if the cancer is a digestive cancer, including colon cancer and pancreatic cancer, or breast cancer, the other anticancer drug is 5FU; if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP; and if the cancer is a pathological condition in which DNA synthesis is dominant, the other anticancer drug is used in combination with a drug that acts on nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from adduct CDDP, the antimetabolite methotrexate, 5FU, etc. (Item X28) The composition according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one of an agent that controls amino acids (particularly methionine, tryptophan, etc.), a lipid agent, or a carbohydrate agent (for carbohydrates, a glucose transporter).(Item X29) A pharmaceutical kit or combination comprising: 1) A) an agent comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for FAP, cancer stem cell (CSC), cancer stem-like cell (CSCLC) marker, and / or ES cell-associated marker, and B) optionally a lipid nanoparticle (LNP), and 2) another anticancer agent different from 1). (Item X30) A pharmaceutical kit or combination according to any one of the above items, characterized in that it treats or prevents cancer. (Item X31) A pharmaceutical kit or combination according to any one of the above items, further comprising the features of any one or more of items X1 to X28. (Item X32) A composition according to any one of the above items, or a pharmaceutical kit or combination according to any one of the above items, characterized in that the mRNA is administered by intravenous injection. (Item X33) A composition according to any one of the above items, or a pharmaceutical kit or combination according to any one of the above items, wherein the treatment includes prevention and / or treatment of cancer recurrence and / or metastasis. (Item XA1) For treating or preventing cancer: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for a cancer stem cell (CSC), cancer stem-like cell (CSCLC) marker, and / or ES cell-associated marker, optionally combined with a lipid nanoparticle (LNP). (Item X1A) The mRNA according to any one of the above items, wherein the cancer stem cell (CSC) marker, cancer stem cell-like cell (CSCLC) marker, and / or ES cell-associated marker is a cancer stem cell (CSC) marker. (Item X1B) The mRNA according to any one of the above items, wherein the cancer stem cell (CSC) marker, cancer stem cell-like cell (CSCLC) marker, and / or ES cell-associated marker is a cancer stem cell (CSCLC) marker. (Item X1C) The mRNA according to any one of the above items, wherein the cancer stem cell (CSC), cancer stem cell-like cell (CSCLC) marker, and / or ES cell-associated marker is a cancer stem cell (CSCLC) marker.(Item XA2) The mRNA according to any one of the preceding items, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item XA3) The mRNA according to any one of the preceding items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item XA4) The mRNA according to any one of the preceding items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item XA5) The mRNA according to any one of the preceding items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item XA6) The mRNA according to any one of the preceding items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item XA7) The mRNA according to any one of the preceding items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item XA8) The CSC markers are CD133 (PROM1), LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5), EpCAM (Epithelial Cell Adhesion Molecule), CD13 / APN, CD24, ALDH (ALDH1A1), and CD34. ＋ / CD38 －, CD123 (IL-3 receptor α), CD44v, CD90 (Thy-1) and those described in List Z. (Item XA8A) The mRNA of any one of the above items, wherein the CSCLC marker is selected from the group consisting of CD133, EGFR / Her2 / neu, CD24, Claudin18.2, Claudin6, FGFR, NRP, c-Met, CD13 / APN, EpCAM, LGR5, CD44v, CD24 and those described in List Z. (Item XA8B) The mRNA of any one of the above items, wherein the ES cell-associated marker is selected from the group consisting of OCT, SOX and those described in List Z. (Item XA9) The mRNA according to any one of the above items, wherein the CAR is encoded by the nucleic acid sequence of SEQ ID NO: 22, 24, 26, 28, 30, 32, 34, or 36, or a modified sequence thereof, or comprises the amino acid sequence of SEQ ID NO: 23, 25, 27, 29, 31, 33, 35, or 37, or a modified version thereof. (Item XA10) The mRNA according to any one of the above items, wherein the CAR comprises an extracellular domain portion for the cancer stem cell (CSC), cancer stem-like cell (CSCLC) marker and / or ES cell-associated marker. (Item XA11) The mRNA according to any one of the above items, wherein the CAR comprises an extracellular domain portion for the cancer stem cell (CSC), cancer stem-like cell (CSCLC) marker and / or ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item XA12) The mRNA according to any one of the above items, wherein the CAR comprises at least one selected from the group consisting of a CD8 leader sequence, a FAP scFv, a CD8a hinge, a CD8a transmembrane region, and a 4-1BB cytoplasmic domain. (Item XA13) The mRNA according to any one of the above items, wherein the cancer is a cancer whose treatment is promoted by treating cancer stem cells. (Item XA14) The mRNA according to any one of the above items, wherein the cancer is a solid cancer.(Item XA15) The mRNA according to any one of the above items, which is delivered to cancer stem cells. (Item XA16) The mRNA according to any one of the above items, which is for inducing T cells in a subject. (Item XA17) The mRNA according to any one of the above items, which is used in combination with another anticancer drug. (Item XA18) The mRNA according to any one of the above items, wherein the other anticancer drug is directed against solid cancer. (Item XA19) The mRNA according to any one of the above items, wherein the other anticancer drug is one known to be effective against the cancer afflicting the subject. (Item XA20) The mRNA according to any one of the above items, used in combination with an anticancer drug (such as 5-FU), an immune checkpoint agonist (such as PD-1 antibody, PD-L1 antibody, CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, CCR4). (Item XA21) The mRNA according to any one of the above items, used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item XA22) The mRNA according to any one of the above items, used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item XA23) The mRNA according to any one of the above items, used in combination with at least one selected from the group consisting of those that target tumor cells themselves, those that target stromal cells, and those that regulate immunity. (Item XA24) The mRNA according to any one of the preceding items, wherein the substance targeting the tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (anticancer drugs of low molecular weight compounds), molecular targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid pharmaceuticals, microRNA, aptamers, cross-linked DNA, etc.(Item XA25) The mRNA according to any one of the preceding items, wherein the substance targeting stromal cells comprises at least one selected from the group consisting of an anti-FGF antibody of FGFR against fibroblasts, an anti-PDGF antibody, an inhibitor thereof, a small molecule, etc. (Item XA26) The mRNA according to any one of the preceding items, wherein the substance regulating immunity comprises at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances acting on the epigenome, substances acting on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals (e.g., IL2) of regulatory T cells (e.g., anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item XA27) The mRNA according to any one of the above items, wherein the other anticancer drug is 5FU if the cancer is a digestive cancer, including colon cancer and pancreatic cancer, or breast cancer; the other anticancer drug is CDDP, a platinum compound, if the cancer is melanoma or breast cancer; and the other anticancer drug is used in combination with a drug that acts on nucleic acid metabolism, or a drug that inhibits DNA synthesis, such as CDDP adduct, the antimetabolite methotrexate, or 5FU, if the cancer is a pathological condition in which DNA synthesis is dominant. (Item XA28) The mRNA according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one agent that regulates amino acids (particularly methionine, tryptophan, etc.), lipids, or carbohydrates (e.g., glucose transporters). (Item XA29) The mRNA according to any one of the above items, wherein the mRNA is administered intravenously. (Item XA33) The mRNA according to any one of the above items, wherein the treatment includes prevention and / or treatment of cancer recurrence and / or metastasis.(Item XB1) Use of A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for a cancer stem cell (CSC), cancer stem-like cell (CSCLC) marker, and / or ES cell-associated marker, and optionally B) a lipid nanoparticle (LNP) in a method for manufacturing a medicament for treating or preventing cancer. (Item XB1A) The use according to any one of the above items, wherein the cancer stem cell (CSC) marker, cancer stem-like cell (CSCLC) marker, and / or ES cell-associated marker is a cancer stem cell (CSC) marker. (Item XB1B) The use according to any one of the above items, wherein the cancer stem cell (CSC) marker, cancer stem cell-like cell (CSCLC) marker, and / or ES cell-associated marker is a cancer stem cell (CSCLC) marker. (Item XB1C) The use according to any one of the above items, wherein the cancer stem cell (CSC) marker, cancer stem cell-like cell (CSCLC) marker, and / or ES cell-associated marker is an ES cell-associated marker. (Item XB2) The use according to any one of the preceding items, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item XB3) The use according to any one of the preceding items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item XB4) The use according to any one of the preceding items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item XB5) The use according to any one of the preceding items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item XB6) The use according to any one of the preceding items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item XB7) The use according to any one of the preceding items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol.(Item XB8) The CSC markers are CD133 (PROM1), LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5), EpCAM (Epithelial Cell Adhesion Molecule), CD13 / APN, CD24, ALDH (ALDH1A1), and CD34. ＋ / CD38 －, CD123 (IL-3 receptor α), CD44v, CD90 (Thy-1) and those described in List Z. (Item X8A) The use of any one of the above items, wherein the CSCLC marker is selected from the group consisting of CD133, EGFR / Her2 / neu, CD24, Claudin18.2, Claudin6, FGFR, NRP, c-Met, CD13 / APN, EpCAM, LGR5, CD44v, CD24 and those described in List Z. (Item X8B) The use of any one of the above items, wherein the ES cell-associated marker is selected from the group consisting of OCT, SOX and those described in List Z. (Item XB9) The use according to any one of the above items, wherein the CAR is encoded by the nucleic acid sequence set forth in SEQ ID NO: 22, 24, 26, 28, 30, 32, 34, or 36, or a modified sequence thereof, or comprises the amino acid sequence set forth in SEQ ID NO: 23, 25, 27, 29, 31, 33, 35, or 37, or a modified version thereof. (Item XB10) The use according to any one of the above items, wherein the CAR comprises an extracellular domain portion for the cancer stem cell (CSC), cancer stem-like cell (CSCLC) marker and / or ES cell-associated marker. (Item XB11) The use according to any one of the above items, wherein the CAR comprises an extracellular domain portion for the cancer stem cell (CSC), cancer stem-like cell (CSCLC) marker and / or ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item XB12) The use according to any one of the above items, wherein the CAR comprises at least one selected from the group consisting of a CD8 leader sequence, a FAP scFv, a CD8a hinge, a CD8a transmembrane region, and a 4-1BB cytoplasmic domain. (Item XB13) The use according to any one of the above items, wherein the cancer is a cancer whose treatment is promoted by treating cancer stem cells. (Item XB14) The use according to any one of the above items, wherein the cancer is a solid cancer.(Item XB15) The use according to any one of the above items, wherein the medicament is delivered to cancer stem cells. (Item XB16) The use according to any one of the above items, wherein the medicament is for inducing T cells in a subject. (Item XB17) The use according to any one of the above items, wherein the medicament is used in combination with another anticancer drug. (Item XB18) The use according to any one of the above items, wherein the other anticancer drug is for solid cancer. (Item XB19) The use according to any one of the above items, wherein the other anticancer drug is one known to be effective against the cancer afflicting the subject. (Item XB20) The use according to any one of the above items, wherein the medicament is used in combination with an anticancer drug (such as 5-FU), an immune checkpoint agonist (such as PD-1 antibody, PD-L1 antibody, or CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item XB21) The use according to any one of the above items, wherein the medicament is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item XB22) The use according to any one of the above items, wherein the medicament is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item XB23) The use according to any one of the above items, wherein the medicament is used in combination with at least one selected from the group consisting of medicaments that target tumor cells themselves, medicaments that target stromal cells, and medicaments that regulate immunity. (Item XB24) The use according to any one of the preceding items, wherein the substance targeting the tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (low molecular weight compound anticancer drugs), molecular targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid drugs, microRNA, aptamers, cross-linked DNA, etc.(Item XB25) The use according to any one of the preceding items, wherein the substance targeting stromal cells comprises at least one selected from the group consisting of an anti-FGF antibody of FGFR against fibroblasts, an anti-PDGF antibody, an inhibitor thereof, a small molecule, etc. (Item XB26) The use according to any one of the preceding items, wherein the substance regulating immunity comprises at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), and substances acting on the epigenome, substances acting on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as downstream hubs in Tregs, such as ZAP70), and molecular targeted drugs against upstream signals of regulatory T cells (e.g., IL2) (e.g., anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item XB27) The use according to any one of the above items, wherein the other anticancer agent is 5FU if the cancer is a gastrointestinal cancer, including colon cancer and pancreatic cancer, or breast cancer; the other anticancer agent is the platinum compound CDDP if the cancer is melanoma or breast cancer; and the other anticancer agent is used in combination with a drug that acts on nucleic acid metabolism, or a drug that inhibits DNA synthesis, such as CDDP adduct, the antimetabolite methotrexate, or 5FU, if the cancer is a pathological condition in which DNA synthesis is dominant. (Item XB28) The use according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one agent that controls amino acids (e.g., methionine, tryptophan, etc.), lipids, or carbohydrates (e.g., glucose transporters). (Item XB32) The use according to any one of the above items, wherein the mRNA is administered intravenously. (Item XB33) The use according to any one of the above items, wherein the treatment includes prevention and / or treatment of cancer recurrence and / or metastasis.(Item XC1) A method for treating or preventing cancer, comprising administering to a subject an effective amount of a composition comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for a cancer stem cell (CSC) marker, a cancer stem-like cell (CSCLC) marker, and / or an ES cell-associated marker; and B) optionally, a lipid nanoparticle (LNP). (Item XC1A) The method of any one of the above items, wherein the cancer stem cell (CSC) marker, a cancer stem-like cell (CSCLC) marker, and / or an ES cell-associated marker is a cancer stem cell (CSC) marker. (Item XC1B) The method of any one of the above items, wherein the cancer stem cell (CSC) marker, a cancer stem cell-like cell (CSCLC) marker, and / or an ES cell-associated marker is a cancer stem cell (CSCLC). (Item XC1C) The method of any one of the above items, wherein the cancer stem cell (CSC) marker, a cancer stem cell-like cell (CSCLC) marker, and / or an ES cell-associated marker is an ES cell-associated marker. (Item XC2) The method of any one of the above items, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item XC3) The method of any one of the above items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item XC4) The method of any one of the above items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item XC5) The method of any one of the above items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item XC6) The method of any one of the above items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item XC7) The method according to any one of the preceding items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol.(Item XC8) The CSC markers are CD133 (PROM1), LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5), EpCAM (Epithelial Cell Adhesion Molecule), CD13 / APN, CD24, ALDH (ALDH1A1), and CD34. ＋ / CD38 －, CD123 (IL-3 receptor α), CD44v, CD90 (Thy-1) and those described in List Z. (Item XC8A) The method of any one of the above items, wherein the CSCLC marker is selected from the group consisting of CD133, EGFR / Her2 / neu, CD24, Claudin18.2, Claudin6, FGFR, NRP, c-Met, CD13 / APN, EpCAM, LGR5, CD44v, CD24 and those described in List Z. (Item XC8B) The method of any one of the above items, wherein the ES cell-associated marker is selected from the group consisting of OCT, SOX and those described in List Z. (Item XC9) The method of any one of the above items, wherein the CAR is encoded by the nucleic acid sequence of SEQ ID NO: 22, 24, 26, 28, 30, 32, 34, or 36, or a modified sequence thereof, or comprises the amino acid sequence of SEQ ID NO: 23, 25, 27, 29, 31, 33, 35, or 37, or a modified version thereof. (Item XC10) The method of any one of the above items, wherein the CAR comprises an extracellular domain portion for the cancer stem cell (CSC), cancer stem-like cell (CSCLC) marker and / or ES cell-associated marker. (Item XC11) The method of any one of the above items, wherein the CAR comprises an extracellular domain portion for the cancer stem cell (CSC), cancer stem-like cell (CSCLC) marker and / or ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item XC12) The method according to any one of the above items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, a FAP scFv, a CD8a hinge, a CD8a transmembrane region, and a 4-1BB cytoplasmic domain. (Item XC13) The method according to any one of the above items, wherein the cancer is a cancer whose treatment is promoted by treating cancer stem cells. (Item XC14) The method according to any one of the above items, wherein the cancer is a solid cancer.(Item XC15) The method of any one of the above items, wherein the composition is delivered to cancer stem cells. (Item XC16) The method of any one of the above items, wherein the composition is for inducing T cells in a subject. (Item XC17) The method of any one of the above items, wherein the composition is used in combination with another anticancer drug. (Item XC18) The method of any one of the above items, wherein the other anticancer drug is directed against a solid cancer. (Item XC19) The method of any one of the above items, wherein the other anticancer drug is known to be effective against the cancer afflicting the subject. (Item XC20) The method of any one of the above items, wherein the composition is used in combination with an anticancer drug (such as 5-FU), an immune checkpoint agonist (such as PD-1 antibody, PD-L1 antibody, or CTLA4 antibody), and an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item XC21) The method of any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item XC22) The method of any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item XC23) The method of any one of the above items, wherein the composition is used in combination with at least one selected from the group consisting of agents that target tumor cells themselves, agents that target stromal cells, and agents that regulate immunity. (Item XC24) The method of any one of the above items, wherein the agent that targets tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (low-molecular-weight compound anticancer drugs), molecular targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid drugs, microRNA, aptamers, cross-linked DNA, etc.(Item XC25) The method according to any one of the preceding items, wherein the substance targeting stromal cells comprises at least one selected from the group consisting of an anti-FGF antibody of FGFR against fibroblasts, an anti-PDGF antibody, an inhibitor thereof, a small molecule, etc. (Item XC26) The method according to any one of the preceding items, wherein the substance regulating immunity comprises at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances acting on the epigenome, substances acting on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as downstream hubs in Tregs, such as ZAP70), and molecular targeted drugs against upstream signals (e.g., IL2) of regulatory T cells (e.g., anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item XC27) The method according to any one of the above items, wherein the other anticancer agent is 5FU if the cancer is a digestive cancer, including colon cancer and pancreatic cancer, or breast cancer; the other anticancer agent is the platinum compound CDDP if the cancer is melanoma or breast cancer; and the other anticancer agent is used in combination with a drug that acts on nucleic acid metabolism, or a drug that inhibits DNA synthesis, such as CDDP adduct, the antimetabolite methotrexate, or 5FU, if the cancer is a pathological condition in which DNA synthesis is dominant. (Item XC28) The method according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one agent that controls amino acids (particularly methionine, tryptophan, etc.), lipids, or carbohydrates (for carbohydrates, glucose transporters). (Item XC29) The method according to any one of the above items, wherein the mRNA is administered intravenously. (Item XC30) The method according to any one of the above items, wherein the treatment includes prevention and / or treatment of cancer recurrence and / or metastasis.

[0006] <Methylated mRNA CAR> (Item Y1) A composition for treating or preventing cancer, comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the mRNA is at least partially methylated; and B) optionally, a lipid nanoparticle (LNP). (Item Y2) The composition according to item Y above, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item Y3) The composition according to any one of the above, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item Y4) The composition according to any one of the above, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item Y5) The composition according to any one of the above items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item Y6) The composition according to any one of the above items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item Y7) The composition according to any one of the above items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item Y8) The composition according to any one of the above items, wherein the CAR is directed against FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item Y9) The composition according to any one of the above items, which is encoded by the nucleic acid sequence set forth in SEQ ID NO: 1, 3, 22, 24, 26, 28, 30, 32, 34 or 36, or a modified sequence thereof, or which comprises the amino acid sequence set forth in SEQ ID NO: 2, 4, 23, 25, 27, 29, 31, 33, 35 or 37, or a modified version thereof.(Item Y10) The composition of any one of the above items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item Y11) The composition of any one of the above items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item Y12) The composition of any one of the above items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, an FAP scFv, a CD8a hinge, a CD8a transmembrane region, and a 4-1BB cytoplasmic domain. (Item Y13) The composition according to any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)) and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item Y14) The composition according to any one of the above items, wherein the cancer is a solid cancer. (Item Y15) The composition according to any one of the above items, wherein the composition is delivered to FAP and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item Y16) The composition according to any one of the above items, wherein the composition is for inducing T cells in a subject. (Item Y17) The composition according to any one of the above items, wherein the composition is used in combination with another anticancer agent. (Item Y18) The composition according to any one of the above items, wherein the other anticancer agent is directed against a solid cancer. (Item Y19) The composition according to any one of the above items, wherein the other anticancer drug is known to be effective against the cancer from which the subject suffers.(Item Y20) The composition according to any one of the above items, wherein the composition is used in combination with an anticancer agent (such as 5-FU), an immune checkpoint agonist (such as a PD-1 antibody, a PD-L1 antibody, or a CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item Y21) The composition according to any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item Y22) The composition according to any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item Y23) The composition according to any one of the above items, wherein the composition is used in combination with at least one selected from the group consisting of compositions that target tumor cells themselves, compositions that target stromal cells, and compositions that regulate immunity. (Item Y24) The composition according to any one of the above items, wherein the substance targeting tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (low-molecular-weight compound anticancer drugs), molecularly targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid pharmaceuticals, microRNA, aptamers, cross-linked DNA, etc. (Item Y25) The composition according to any one of the above items, wherein the substance targeting stromal cells includes at least one selected from the group consisting of anti-FGF antibodies against FGFR for fibroblasts, anti-PDGF antibodies, inhibitors thereof, small molecules, etc.(Item Y26) The composition according to any one of the preceding items, wherein the substance that regulates immunity includes at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals of regulatory T cells (e.g., IL2) (anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item Y27) The composition according to any one of the above items, wherein if the cancer is a digestive cancer, including colon cancer and pancreatic cancer, or breast cancer, the other anticancer drug is 5FU; if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP; and if the cancer is a pathological condition in which DNA synthesis is dominant, the other anticancer drug is used in combination with a drug that acts on the regulation of nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from adduct CDDP, the antimetabolite methotrexate, 5FU, etc. (Item Y28) The composition according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one of an agent that regulates amino acids (particularly methionine, tryptophan, etc.), a lipid regulator, or a carbohydrate regulator (for carbohydrates, a glucose transporter). (Item Y29) A pharmaceutical kit or combination comprising: 1) A) an agent comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the mRNA is at least partially methylated, and B) optionally a lipid nanoparticle (LNP), and 2) another anticancer agent different from 1). (Item Y30) A pharmaceutical kit or combination according to any one of the above items, characterized in that it treats or prevents cancer. (Item Y31) A pharmaceutical kit or combination according to any one of the above items, further comprising the features described in any one or more of items Y1 to Y28.(Item Y32) The composition according to any one of the above items, or the pharmaceutical kit or combination according to any one of the above items, wherein the mRNA is administered by intravenous injection. (Item Y33) The composition according to any one of the above items, or the pharmaceutical kit or combination according to any one of the above items, wherein the treatment includes preventing and / or treating cancer recurrence and / or metastasis. (Item Y34) The composition according to any one of the above items, or the pharmaceutical kit or combination according to any one of the above items, wherein the methylation includes that of adenine. (Item Y101) The composition according to any one of the above items, or the pharmaceutical kit or combination according to any one of the above items, wherein the composition is used in combination with a demethylase inhibitor. (Item Y102) The composition according to any one of the preceding items, or the pharmaceutical kit or combination according to any one of the preceding items, wherein the demethylase inhibitor is a compound that inhibits the activity of FTO (fat mass and obesity-associated protein) and ALKBH5 (AlkB homolog 5), specifically, FB23-2, CS1, MO-I-500, R-2-hydroxyglutarate (R-2HG), meclofenamic acid (MA), entacapone, Dac51, or viridicatin. (Item YA1) A) mRNA for treating or preventing cancer, comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the mRNA is at least partially methylated, and B) the mRNA is used together with a lipid nanoparticle (LNP) as needed. (Item YA2) The mRNA according to the above item, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item YA3) The mRNA according to any one of the above items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol.(Item YA4) The mRNA according to any one of the preceding items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item YA5) The mRNA according to any one of the preceding items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item YA6) The mRNA according to any one of the preceding items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item YA7) The mRNA according to any one of the preceding items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item YA8) The mRNA according to any one of the preceding items, wherein the CAR is directed against FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item YA9) The mRNA according to any one of the preceding items, wherein the CAR is encoded by the nucleic acid sequence set forth in SEQ ID NO: 1, 3, 22, 24, 26, 28, 30, 32, 34 or 36, or a modified sequence thereof, or comprises the amino acid sequence set forth in SEQ ID NO: 2, 4, 23, 25, 27, 29, 31, 33, 35 or 37, or a modified sequence thereof. (Item YA10) The mRNA according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion directed against FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item YA11) The mRNA according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137).(Item YA12) The mRNA according to any one of the above items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, FAP scFv, CD8a hinge, CD8a transmembrane region, and 4-1BB cytoplasmic domain. (Item YA13) The mRNA according to any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)) and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item YA14) The mRNA according to any one of the above items, wherein the cancer is a solid cancer. (Item YA15) The mRNA according to any one of the above items, which is delivered to FAP and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item YA16) The mRNA according to any one of the above items, which is used to induce T cells in a subject. (Item YA17) The mRNA according to any one of the above items, which is used in combination with another anticancer drug. (Item YA18) The mRNA according to any one of the above items, wherein the other anticancer drug is directed against a solid cancer. (Item YA19) The mRNA according to any one of the above items, wherein the other anticancer drug is known to be effective against the cancer afflicting the subject. (Item YA20) The mRNA according to any one of the above items, which is used in combination with a cancer drug (such as 5-FU), an immune checkpoint agonist (such as PD-1 antibody, PD-L1 antibody, CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, CCR4). (Item YA21) The mRNA according to any one of the above items, which is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item YA22) The mRNA according to any one of the above items, which is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody.(Item YA23) The mRNA of any one of the above items, used in combination with at least one selected from the group consisting of those targeting tumor cells themselves, those targeting stromal cells, and those that regulate immunity. (Item YA24) The mRNA of any one of the above items, wherein the targeting of tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (low-molecular-weight compound anticancer drugs), molecularly targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid drugs, microRNA, aptamers, cross-linked DNA, etc. (Item YA25) The mRNA of any one of the above items, wherein the targeting of stromal cells includes at least one selected from the group consisting of anti-FGF antibodies against FGFR in fibroblasts, anti-PDGF antibodies, inhibitors thereof, small molecules, etc. (Item YA26) The mRNA according to any one of the preceding items, wherein the substance that regulates immunity includes at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals of regulatory T cells (e.g., IL2) (anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item YA27) The mRNA according to any one of the above items, wherein if the cancer is a digestive cancer including colon cancer and pancreatic cancer, or breast cancer, the other anticancer drug is 5FU; if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP; if the cancer is a pathological condition in which DNA synthesis is dominantly effective, the other anticancer drug is used in combination with a drug that acts on the control of nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from the group consisting of adduct CDDP, antimetabolite methotrexate, and 5FU.(Item YA28) The mRNA according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one of an agent regulating amino acids (particularly methionine, tryptophan, etc.), an agent regulating lipids, or an agent regulating carbohydrates (for carbohydrates, a glucose transporter). (Item YA32) The mRNA according to any one of the above items, wherein the mRNA is administered intravenously. (Item YA33) The mRNA according to any one of the above items, wherein the treatment includes prevention and / or treatment of cancer recurrence and / or metastasis. (Item YA34) The mRNA according to any one of the above items, wherein the methylation includes that of adenine. (Item YA101) The mRNA according to any one of the above items, wherein the mRNA is used in combination with a demethylase inhibitor. (Item YA102) The mRNA according to any one of the preceding items, wherein the demethylase inhibitor is a compound that inhibits the activity of FTO (Fat mass and obesity-associated protein) and ALKBH5 (AlkB homolog 5), specifically, FB23-2, CS1, MO-I-500, R-2-hydroxyglutarate (R-2HG), meclofenamic acid (MA), entacapone, Dac51, or viridicatin. (Item YB1) A) Use of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for the manufacture of a medicament for treating or preventing cancer, wherein the mRNA is at least partially methylated, and the mRNA is B) optionally used together with a lipid nanoparticle (LNP). (Item YB2) The use according to the above item, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item YB3) The use according to any one of the above items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol.(Item YB4) The use according to any one of the preceding items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item YB5) The use according to any one of the preceding items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item YB6) The use according to any one of the preceding items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item YB7) The use according to any one of the preceding items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item YB8) The use according to any one of the above items, wherein the CAR is directed against FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item YB9) The use according to any one of the above items, wherein the nucleic acid sequence encoding the CAR is encoded by the nucleic acid sequence set forth in SEQ ID NO: 1, 3, 22, 24, 26, 28, 30, 32, 34, or 36, or a modified sequence thereof, or comprises the amino acid sequence set forth in SEQ ID NO: 2, 4, 23, 25, 27, 29, 31, 33, 35, or 37, or a modified sequence thereof. (Item YB10) The use according to any one of the above items, wherein the CAR comprises an extracellular domain portion directed against FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item YB11) The use according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137).(Item YB12) The use according to any one of the above items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, FAP scFv, CD8a hinge, CD8a transmembrane region, and 4-1BB cytoplasmic domain. (Item YB13) The use according to any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)) and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item YB14) The use according to any one of the above items, wherein the cancer is a solid cancer. (Item YB15) The use according to any one of the above items, wherein the medicament is delivered to FAP and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item YB16) The use according to any one of the above items, wherein the medicament is for inducing T cells in a subject. (Item YB17) The use according to any one of the above items, wherein the medicament is used in combination with another anticancer drug. (Item YB18) The use according to any one of the above items, wherein the other anticancer drug is for solid cancer. (Item YB19) The use according to any one of the above items, wherein the other anticancer drug is known to be effective against the cancer afflicting the subject. (Item YB20) The use according to any one of the above items, wherein the medicament is used in combination with a cancer drug (such as 5-FU), an immune checkpoint agonist (such as PD-1 antibody, PD-L1 antibody, CTLA4 antibody), and an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, CCR4). (Item YB21) The use according to any one of the preceding items, wherein the medicament is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item YB22) The use according to any one of the preceding items, wherein the medicament is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody.(Item YB23) The use according to any one of the preceding items, wherein the pharmaceutical agent is used in combination with at least one selected from the group consisting of agents targeting tumor cells themselves, agents targeting stromal cells, and agents that regulate immunity. (Item YB24) The use according to any one of the preceding items, wherein the agent targeting tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (low-molecular-weight compound anticancer drugs), molecularly targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid drugs, microRNA, aptamers, cross-linked DNA, etc. (Item YB25) The use according to any one of the preceding items, wherein the agent targeting stromal cells includes at least one selected from the group consisting of anti-FGF antibodies against FGFR in fibroblasts, anti-PDGF antibodies, inhibitors thereof, small molecules, etc. (Item YB26) The use according to any one of the preceding items, wherein the substance that regulates immunity includes at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals of regulatory T cells (e.g., IL2) (anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item YB27) The use according to any one of the above items, wherein if the cancer is a digestive cancer including colon cancer or pancreatic cancer, or breast cancer, the other anticancer drug is 5FU; if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP; if the cancer is a pathological condition in which DNA synthesis is dominantly effective, the other anticancer drug is used in combination with a drug that acts on the control of nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from the group consisting of adduct CDDP, the antimetabolite methotrexate, and 5FU.(Item YB28) The use according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one of an agent regulating amino acids (particularly methionine, tryptophan, etc.), an agent regulating lipids, or an agent regulating carbohydrates (for carbohydrates, a glucose transporter). (Item YB32) The use according to any one of the above items, wherein the medicament is administered intravenously. (Item YB33) The use according to any one of the above items, wherein the treatment includes prevention and / or treatment of cancer recurrence and / or metastasis. (Item YB34) The use according to any one of the above items, wherein the methylation includes that of adenine. (Item YB101) The use according to any one of the above items, wherein the medicament is used in combination with a demethylase inhibitor. (Item YB102) The use according to any one of the preceding items, wherein the demethylase inhibitor is a compound that inhibits the activity of FTO (fat mass and obesity-associated protein) and ALKBH5 (AlkB homolog 5), specifically FB23-2, CS1, MO-I-500, R-2-hydroxyglutarate (R-2HG), meclofenamic acid (MA), entacapone, Dac51, or viridicatin. (Item YC1) A method for treating or preventing cancer, comprising administering to a subject an effective amount of a composition comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the mRNA is at least partially methylated; and B) optionally, a lipid nanoparticle (LNP). (Item YC2) The method according to any one of the above items, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item YC3) The method according to any one of the above items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol.(Item YC4) The method according to any one of the preceding items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item YC5) The method according to any one of the preceding items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item YC6) The method according to any one of the preceding items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item YC7) The method according to any one of the preceding items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item YC8) The method of any one of the above items, wherein the CAR is directed against FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item YC9) The method of any one of the above items, wherein the CAR is encoded by the nucleic acid sequence set forth in SEQ ID NO: 1, 3, 22, 24, 26, 28, 30, 32, 34, or 36, or a modified sequence thereof, or comprises the amino acid sequence set forth in SEQ ID NO: 2, 4, 23, 25, 27, 29, 31, 33, 35, or 37, or a modified sequence thereof. (Item YC10) The method of any one of the above items, wherein the CAR comprises an extracellular domain portion directed against FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item YC11) The method according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137).(Item YC12) The method of any one of the above items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, FAP scFv, CD8a hinge, CD8a transmembrane region, and 4-1BB cytoplasmic domain. (Item YC13) The method of any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)) and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item YC14) The method of any one of the above items, wherein the cancer is a solid cancer. (Item YC15) The method of any one of the above items, wherein the composition is delivered to FAP and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item YC16) The method of any one of the above items, wherein the composition is for inducing T cells in a subject. (Item YC17) The method of any one of the above items, wherein the composition is used in combination with another anticancer drug. (Item YC18) The method of any one of the above items, wherein the other anticancer drug is directed against a solid cancer. (Item YC19) The method of any one of the above items, wherein the other anticancer drug is known to be effective against the cancer afflicting the subject. (Item YC20) The method of any one of the above items, wherein the composition is used in combination with an anticancer drug (such as 5-FU), an immune checkpoint agonist (such as PD-1 antibody, PD-L1 antibody, or CTLA4 antibody), and an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item YC21) The method of any one of the preceding items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item YC22) The method of any one of the preceding items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody.(Item YC23) The method of any one of the above items, wherein the composition is used in combination with at least one selected from the group consisting of those that target tumor cells themselves, those that target stromal cells, and those that regulate immunity. (Item YC24) The method of any one of the above items, wherein the substance that targets tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (low-molecular-weight compound anticancer drugs), molecularly targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid drugs, microRNA, aptamers, cross-linked DNA, etc. (Item YC25) The method of any one of the above items, wherein the substance that targets stromal cells includes at least one selected from the group consisting of anti-FGF antibodies against FGFR in fibroblasts, anti-PDGF bodies, inhibitors thereof, small molecules, etc. (Item YC26) The method according to any one of the preceding items, wherein the substance that controls immunity includes at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals (such as IL2) of regulatory T cells (anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item YC27) The method according to any one of the preceding items, wherein if the cancer is a digestive cancer including colon cancer and pancreatic cancer, or breast cancer, the other anticancer drug is 5FU; if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP; and if the cancer is in a pathological state in which DNA synthesis is dominantly affected, the other anticancer drug is used in combination with a drug that acts on the control of nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from the group consisting of adduct CDDP, the antimetabolite methotrexate, and 5FU.(Item YC28) The method of any one of the above items, wherein the additional agent controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one of an agent that controls amino acids (particularly methionine, tryptophan, etc.), an agent that controls lipids, or an agent that controls carbohydrates (for carbohydrates, a glucose transporter). (Item YC29) A method for treating or preventing a subject, comprising administering to the subject: 1) an effective amount of an agent comprising A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the mRNA is at least partially methylated, and B) optionally a lipid nanoparticle (LNP); and 2) an effective amount of an anticancer agent different from 1). (Item YC30) The method of any one of the above items, characterized in that it treats or prevents cancer. (Item YC31) The method of any one of the above items, further comprising the features of any one or more of Items YC1 to YC28. (Item YC32) The method of any one of the above items, wherein the mRNA is administered by intravenous injection. (Item YC33) The method of any one of the above items, wherein the treatment includes preventing and / or treating cancer recurrence and / or metastasis. (Item YC34) The composition of any one of the above items, or the pharmaceutical kit or combination of any one of the above items, wherein the methylation comprises that of adenine. (Item YC101) The method of any one of the above items, wherein the composition is used in combination with a demethylase inhibitor. (Item YC102) The method according to any one of the preceding items, wherein the demethylase inhibitor is a compound that inhibits the activity of FTO (fat mass and obesity-associated protein) and ALKBH5 (AlkB homolog 5), specifically FB23-2, CS1, MO-I-500, R-2-hydroxyglutarate (R-2HG), meclofenamic acid (MA), entacapone, Dac51, or viridicatin.

[0007] <Polybetaine> (Item Z1) A composition for treating or preventing cancer, comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR); and B) lipid nanoparticles (LNPs) comprising polybetaine. (Item Z1A) A composition for use in improving the delivery efficiency of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), comprising lipid nanoparticles (LNPs) comprising polybetaine. (Item Z2) The composition of any one of items Z above, wherein the LNPs comprise at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item Z3) The composition of any one of the above, wherein the LNPs comprise a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item Z4) The composition of any one of the above, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item Z5) The composition according to any one of the above items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item Z6) The composition according to any one of the above items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item Z7) The composition according to any one of the above items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item Z8) The composition according to any one of the above items, wherein the CAR is directed against FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item Z9) The composition according to any one of the preceding items, wherein the nucleic acid sequence encoding the CAR is encoded by the nucleic acid sequence set forth in SEQ ID NO: 1, 3, 22, 24, 26, 28, 30, 32, 34, or 36, or a modified sequence thereof, or comprises the amino acid sequence set forth in SEQ ID NO: 2, 4, 23, 25, 27, 29, 31, 33, 35, or 37, or a modified sequence thereof.(Item Z10) The composition of any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item Z11) The composition of any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item Z12) The composition of any one of the preceding items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, an FAP scFv, a CD8a hinge, a CD8a transmembrane region, and a 4-1BB cytoplasmic domain. (Item Z13) The composition according to any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)) and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item Z14) The composition according to any one of the above items, wherein the cancer is a solid cancer. (Item Z15) The composition according to any one of the above items, wherein the composition is delivered to FAP and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item Z16) The composition according to any one of the above items, wherein the composition is for inducing T cells in a subject. (Item Z17) The composition according to any one of the above items, wherein the composition is used in combination with another anticancer agent. (Item Z18) The composition according to any one of the above items, wherein the other anticancer agent is directed against a solid cancer. (Item Z19) The composition according to any one of the preceding items, wherein the other anticancer drug is known to be effective against the cancer from which the subject suffers.(Item Z20) The composition according to any one of the above items, wherein the composition is used in combination with an anticancer agent (such as 5-FU), an immune checkpoint agonist (such as a PD-1 antibody, a PD-L1 antibody, or a CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item Z21) The composition according to any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item Z22) The composition according to any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item Z23) The composition according to any one of the above items, wherein the composition is used in combination with at least one selected from the group consisting of compositions that target tumor cells themselves, compositions that target stromal cells, and compositions that regulate immunity. (Item Z24) The composition according to any one of the above items, wherein the substance targeting tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (low-molecular-weight compound anticancer drugs), molecularly targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid pharmaceuticals, microRNA, aptamers, cross-linked DNA, etc. (Item Z25) The composition according to any one of the above items, wherein the substance targeting stromal cells includes at least one selected from the group consisting of anti-FGF antibodies against FGFR for fibroblasts, anti-PDGF antibodies, inhibitors thereof, small molecules, etc.(Item Z26) The composition according to any one of the preceding items, wherein the substance that regulates immunity includes at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals of regulatory T cells (e.g., IL2) (e.g., anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item Z27) The composition according to any one of the above items, wherein if the cancer is a digestive cancer, including colon cancer and pancreatic cancer, or breast cancer, the other anticancer drug is 5FU, if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP, and if the cancer is a pathological condition in which DNA synthesis is dominantly affected, the other anticancer drug is used in combination with a drug that acts on nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from adduct CDDP, the antimetabolite methotrexate, 5FU, etc. (Item Z28) The composition according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one of an agent that controls amino acids (particularly methionine, tryptophan, etc.), a lipid control agent, or a carbohydrate control agent (for carbohydrates, a glucose transporter). (Item Z29) A pharmaceutical kit or combination comprising: 1) an agent comprising A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), and B) lipid nanoparticles (LNPs) comprising polybetaine, and 2) another anticancer agent different from 1). (Item Z30) A pharmaceutical kit or combination according to any one of the above items, characterized in that it treats or prevents cancer. (Item Z31) A pharmaceutical kit or combination according to any one of the above items, further comprising the features of any one or more of items Z1 to Z28. (Item Z32) A composition according to any one of the above items, or a pharmaceutical kit or combination according to any one of the above items, characterized in that the mRNA is administered by intravenous injection.(Item Z33) The composition according to any one of the above items, or the pharmaceutical kit or combination according to any one of the above items, wherein the treatment includes preventing and / or treating cancer recurrence and / or metastasis. (Item ZA1) A) Lipid nanoparticles (LNPs) comprising polybetaine for use in treating or preventing cancer with mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item ZA1A) Lipid nanoparticles (LNPs) comprising polybetaine for improving the delivery efficiency of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item ZA2) The composition according to Item ZA, wherein the LNPs comprise at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item ZA3) The LNPs according to any one of the above items, wherein the LNPs comprise a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item ZA4) The LNP according to any one of the preceding items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item ZA5) The LNP according to any one of the preceding items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item ZA6) The LNP according to any one of the preceding items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item ZA7) The LNP according to any one of the preceding items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item ZA8) The LNP according to any one of the preceding items, wherein the CAR is directed against FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker.(Item ZA9) The LNP according to any one of the preceding items, wherein the nucleic acid sequence encoding the CAR is encoded by the nucleic acid sequence set forth in SEQ ID NO: 1, 3, 22, 24, 26, 28, 30, 32, 34, or 36, or a modified sequence thereof, or comprises the amino acid sequence set forth in SEQ ID NO: 2, 4, 23, 25, 27, 29, 31, 33, 35, or 37, or a modified version thereof. (Item ZA10) The LNP according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item ZA11) The LNP according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item ZA12) The LNP according to any one of the preceding items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, FAP scFv, CD8a hinge, CD8a transmembrane region, and 4-1BB cytoplasmic domain. (Item ZA13) The LNP according to any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)) and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item ZA14) The LNP according to any one of the above items, wherein the cancer is a solid cancer. (Item ZA15) The LNP according to any one of the above items, wherein the mRNA is delivered to FAP and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item ZA16) The LNP according to any one of the above items, wherein the mRNA is for inducing T cells in a subject. (Item ZA17) The LNP according to any one of the above items, wherein the mRNA is used in combination with another anticancer drug.(Item ZA18) The LNP according to any one of the above items, wherein the other anticancer agent is directed against a solid cancer. (Item ZA19) The LNP according to any one of the above items, wherein the other anticancer agent is one known to be effective against the cancer afflicting the subject. (Item ZA20) The LNP according to any one of the above items, wherein the mRNA is used in combination with an anticancer agent (such as 5-FU), an immune checkpoint agonist (such as a PD-1 antibody, a PD-L1 antibody, or a CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item ZA21) The LNP according to any one of the above items, wherein the mRNA is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item ZA22) The LNP according to any one of the preceding items, wherein the mRNA is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item ZA23) The LNP according to any one of the preceding items, wherein the mRNA is used in combination with at least one selected from the group consisting of those targeting tumor cells themselves, those targeting stromal cells, and those that regulate immunity. (Item ZA24) The LNP according to any one of the preceding items, wherein the targeting agent for tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (low-molecular-weight compound anticancer drugs), molecularly targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid drugs, microRNA, aptamers, cross-linked DNA, etc. (Item ZA25) The LNP according to any one of the above items, wherein the substance targeting stromal cells includes at least one selected from the group consisting of an anti-FGF antibody of FGFR against fibroblasts, an anti-PDGF antibody, an inhibitor thereof, a small molecule, and the like.(Item ZA26) The LNP according to any one of the preceding items, wherein the substance that regulates immunity comprises at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., inhibitors of key factors that act as a hub for downstream Tregs, such as endoxan and ZAP70), and molecular targeted drugs against upstream signals of regulatory T cells (such as IL2) (anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item ZA27) The LNP according to any one of the above items, wherein if the cancer is a digestive cancer, including colon cancer and pancreatic cancer, or breast cancer, the other anticancer drug is 5FU; if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP; and if the cancer is a pathological condition in which DNA synthesis is dominant, the other anticancer drug is used in combination with a drug that acts on nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from the group consisting of adduct CDDP, the antimetabolite methotrexate, and 5FU. (Item ZA28) The LNP according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, an agent that controls amino acids (particularly methionine, tryptophan, etc.), a lipid control agent, or a carbohydrate control agent (for carbohydrates, a glucose transporter). (Item ZA32) The LNP according to any one of the preceding items, wherein the mRNA is administered by intravenous injection. (Item ZA33) The LNP according to any one of the preceding items, wherein the treatment includes preventing and / or treating cancer recurrence and / or metastasis. (Item ZB1) A) Use of lipid nanoparticles (LNPs) comprising polybetaine for the manufacture of a medicament for treating or preventing cancer, comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). B) Use of lipid nanoparticles (LNPs) comprising polybetaine for the manufacture of a medicament for improving the delivery efficiency of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR).(Item ZB2) The composition according to any one of the preceding items, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item ZB3) The use according to any one of the preceding items, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item ZB4) The use according to any one of the preceding items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item ZB5) The use according to any one of the preceding items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item ZB6) The use according to any one of the above items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item ZB7) The use according to any one of the above items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item ZB8) The use according to any one of the above items, wherein the CAR is directed against FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item ZB9) The use according to any one of the preceding items, wherein the nucleic acid sequence encoding the CAR is encoded by the nucleic acid sequence set forth in SEQ ID NO: 1, 3, 22, 24, 26, 28, 30, 32, 34, or 36, or a modified sequence thereof, or comprises the amino acid sequence set forth in SEQ ID NO: 2, 4, 23, 25, 27, 29, 31, 33, 35, or 37, or a modified sequence thereof. (Item ZB10) The use according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker.(Item ZB11) The use according to any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item ZB12) The use according to any one of the preceding items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, FAP scFv, CD8a hinge, CD8a transmembrane region, and 4-1BB cytoplasmic domain. (Item ZB13) The use according to any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)) and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item ZB14) The use according to any one of the above items, wherein the cancer is a solid cancer. (Item ZB15) The use according to any one of the above items, wherein the mRNA is delivered to FAP and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item ZB16) The use according to any one of the above items, wherein the mRNA is for inducing T cells in a subject. (Item ZB17) The use according to any one of the above items, wherein the mRNA is used in combination with another anticancer drug. (Item ZB18) The use according to any one of the above items, wherein the other anticancer drug is for a solid cancer. (Item ZB19) The use according to any one of the above items, wherein the other anticancer drug is one that has been found to be effective against the cancer that the subject is suffering from.(Item ZB20) The use according to any one of the above items, wherein the mRNA is used in combination with an anticancer drug (such as 5-FU), an immune checkpoint agonist (such as PD-1 antibody, PD-L1 antibody, or CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZBP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item ZB21) The use according to any one of the above items, wherein the mRNA is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item ZB22) The use according to any one of the above items, wherein the mRNA is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item ZB23) The use according to any one of the above items, wherein the mRNA is used in combination with at least one selected from the group consisting of those that target tumor cells themselves, those that target stromal cells, and those that regulate immunity. (Item ZB24) The use according to any one of the above items, wherein the substance targeting tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (low-molecular-weight compound anticancer drugs), molecularly targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid drugs, microRNA, aptamers, cross-linked DNA, etc. (Item ZB25) The use according to any one of the above items, wherein the substance targeting stromal cells includes at least one selected from the group consisting of anti-FGF antibodies against FGFR against fibroblasts, anti-PDGF antibodies, inhibitors thereof, small molecules, etc.(Item ZB26) The use according to any one of the preceding items, wherein the substance that regulates immunity includes at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, ZBP70, etc., inhibitors of key factors that act as a hub for downstream Tregs), and molecular targeted drugs against upstream signals (e.g., IL2) of regulatory T cells (e.g., anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item ZB27) The use according to any one of the above items, wherein the other anticancer agent is 5FU if the cancer is a gastrointestinal cancer, including colon cancer and pancreatic cancer, or breast cancer; the other anticancer agent is the platinum compound CDDP if the cancer is melanoma or breast cancer; and the other anticancer agent is used in combination with a drug that acts on nucleic acid metabolism, or a drug that inhibits DNA synthesis, such as CDDP adduct, the antimetabolite methotrexate, or 5FU, if the cancer is a pathological condition in which DNA synthesis is dominant. (Item ZB28) The use according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one agent that controls amino acids (particularly methionine, tryptophan, etc.), lipids, or carbohydrates (for carbohydrates, glucose transporters). (Item ZB32) The use according to any one of the above items, wherein the mRNA is administered intravenously. (Item ZB33) The use according to any one of the above items, wherein the treatment includes prevention and / or treatment of cancer recurrence and / or metastasis. (Item ZC1) A method for treating or preventing cancer, comprising administering to a subject an effective amount of a composition comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR); and B) lipid nanoparticles (LNPs) comprising polybetaine.(Item ZC1A) A method for improving the delivery efficiency of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), comprising administering to a subject an effective amount of a composition comprising lipid nanoparticles (LNPs) comprising polybetaine. (Item ZC2) The method according to any one of the above items, wherein the LNPs comprise at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item ZC3) The method according to any one of the above items, wherein the LNPs comprise a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol. (Item ZC4) The method according to any one of the above items, wherein the PEGylated lipid comprises ALC-0159 (2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). (Item ZC5) The method according to any one of the above items, wherein the ionizable lipid comprises ALC-0315 ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate). (Item ZC6) The method according to any one of the above items, wherein the phospholipid comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). (Item ZC7) The method according to any one of the above items, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol. (Item ZC8) The method according to any one of the above items, wherein the CAR is directed against FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker. (Item ZC9) The method of any one of the above items, wherein the nucleic acid sequence encoding the CAR is encoded by the nucleic acid sequence set forth in SEQ ID NO: 1, 3, 22, 24, 26, 28, 30, 32, 34, or 36, or a modified sequence thereof, or comprises the amino acid sequence set forth in SEQ ID NO: 2, 4, 23, 25, 27, 29, 31, 33, 35, or 37, or a modified version thereof. (Item ZC10) The method of any one of the above items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker.(Item ZC11) The method of any one of the preceding items, wherein the CAR comprises an extracellular domain portion for FAP and / or a cancer stem cell (CSC) marker and / or a cancer stem cell-like cell (CSCLC) marker and / or an ES cell-associated marker, and an intracellular domain portion comprising at least one selected from the group consisting of CD3ζ, CD8a, and 4-1BB (CD137). (Item ZC12) The method of any one of the preceding items, wherein the CAR comprises at least one selected from the group consisting of a CD8-leader sequence, FAP scFv, CD8a hinge, CD8a transmembrane region, and 4-1BB cytoplasmic domain. (Item ZC13) The method of any one of the above items, wherein the cancer is a cancer associated with FAP (or CAF (cancer-associated fibroblast)) and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item ZC14) The method of any one of the above items, wherein the cancer is a solid cancer. (Item ZC15) The method of any one of the above items, wherein the composition is delivered to FAP and / or cancer stem cells (CSC) and / or cancer stem-like cells (CSCLC) and / or ES cells or ES cell-like cells. (Item ZC16) The method of any one of the above items, wherein the composition is for inducing T cells in a subject. (Item ZC17) The method of any one of the above items, wherein the composition is used in combination with another anticancer agent. (Item ZC18) The method of any one of the above items, wherein the other anticancer agent is for a solid cancer. (Item ZC19) The method according to any one of the preceding items, wherein the other anticancer drug is one that has been proven to be effective against the cancer from which the subject suffers.(Item ZC20) The method of any one of the above items, wherein the composition is used in combination with an anticancer drug (such as 5-FU), an immune checkpoint agonist (such as PD-1 antibody, PD-L1 antibody, or CTLA4 antibody), an inhibitor of a T cell immunoregulatory signal molecule (e.g., ZAP70), or an antibody or inhibitor of a chemokine (such as CXCR4, CXCR8, CCL1, CCLR8, or CCR4). (Item ZC21) ​​The method of any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, or a CTLA4 antibody. (Item ZC22) The method of any one of the above items, wherein the composition is used in combination with 5-FU, a PD-1 antibody, and a CTLA4 antibody. (Item ZC23) The method of any one of the above items, wherein the composition is used in combination with at least one selected from the group consisting of compositions that target tumor cells themselves, compositions that target stromal cells, and compositions that regulate immunity. (Item ZC24) The method according to any one of the above items, wherein the substance targeting the tumor cells themselves includes at least one selected from the group consisting of chemotherapeutic agents (low molecular weight compound anticancer drugs), molecular targeted drugs (anti-HER2 antibodies, anti-EGFR antibodies, anti-TGFb antibodies, etc., or inhibitors thereof, small molecules, etc.), radiation exposure (X-rays, particle beams, heavy particle beams, proton beams, electron beams, etc.), boron, nucleic acid pharmaceuticals, microRNA, aptamers, cross-linked DNA, etc. (Item ZC25) The method according to any one of the above items, wherein the substance targeting the stromal cells includes at least one selected from the group consisting of anti-FGF antibodies of FGFR against fibroblasts, anti-PDGF antibodies, inhibitors thereof, small molecules, etc.(Item ZC26) The method according to any one of the preceding items, wherein the substance that controls immunity includes at least one selected from the group consisting of immunosuppressants (e.g., cyclosporine, endoxan, FK228, etc.), substances that act on the epigenome, substances that act on regulatory T cells (e.g., endoxan, inhibitors of key factors that act as a hub for downstream Tregs, such as ZAP70), and molecular targeted drugs against upstream signals (such as IL2) of regulatory T cells (anti-IL2 antibodies, anti-TGFb antibodies that conversely positively regulate IL2 itself, or inhibitors thereof (e.g., small molecules, agonists), etc.). (Item ZC27) The method according to any one of the above items, wherein if the cancer is a digestive cancer, including colon cancer and pancreatic cancer, or breast cancer, the other anticancer drug is 5FU, if the cancer is melanoma or breast cancer, the other anticancer drug is the platinum compound CDDP, and if the cancer is a pathological condition in which DNA synthesis is dominantly affected, the other anticancer drug is used in combination with a drug that acts on nucleic acid metabolism, or a drug that inhibits DNA synthesis, selected from adduct CDDP, the antimetabolite methotrexate, 5FU, etc. (Item ZC28) The method according to any one of the above items, wherein the additional drug controls the nutritional balance between immune cells and phagocytic cancer cells in the body, for example, at least one of an agent that controls amino acids (particularly methionine, tryptophan, etc.), a lipid control agent, or a carbohydrate control agent (for carbohydrates, a glucose transporter). (Item ZC29) A pharmaceutical kit or combination comprising: 1) an agent comprising A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), and B) lipid nanoparticles (LNPs) comprising polybetaine, and 2) another anticancer agent different from 1). (Item ZC30) A pharmaceutical kit or combination according to any one of items ZC above, characterized in that it is used to treat or prevent cancer. (Item ZC31) A pharmaceutical kit or combination according to any one of the above items, further comprising the features of any one or more of items ZC1 to ZC28. (Item ZC32) A composition according to any one of the above items, or a pharmaceutical kit or combination according to any one of the above items, characterized in that the mRNA is administered by intravenous injection.(Item ZC33) The composition according to any one of the preceding items, or the pharmaceutical kit or combination according to any one of the preceding items, wherein the treatment includes prevention and / or treatment of cancer recurrence and / or metastasis.

[0008] <Suppression of Mif-CD74 expression> (Item W1) A composition for inhibiting tumor immune evasion, comprising a Mif inhibitor and / or a CD74 inhibitor. (Item W2) The composition according to any one of the above items, wherein the inhibitor suppresses expression of Mif and / or CD74. (Item W3) A composition for improving delivery of chimeric antigen receptor (CAR) T cells, comprising an inhibitor targeted to Mif and / or CD74, and CAR-T cells comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item W4) A composition for treating or preventing cancer, comprising an inhibitor targeted to Mif, an inhibitor targeted to CD74, mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), and optionally a lipid nanoparticle (LNP). (Item W4) The composition according to any one of the above items, wherein the inhibitor is a protein, polypeptide, oligopeptide, peptide, polynucleotide, oligonucleotide, nucleotide, nucleic acid (including, for example, DNA such as cDNA and genomic DNA, and RNA such as mRNA), polysaccharide, oligosaccharide, lipid, small organic molecule (e.g., hormone, ligand, signaling substance, small organic molecule, molecule synthesized by combinatorial chemistry, small molecule that can be used as a pharmaceutical (e.g., small molecule ligand, etc.)), or a composite molecule thereof. (Item W5) The composition according to any one of the above items, wherein the inhibitor comprises an antibody or an antibody fragment. (Item WA1) A Mif inhibitor and / or CD74 inhibitor for inhibiting tumor immune evasion. (Item WA2) The inhibitor according to any one of the above items, wherein the inhibitor suppresses the expression of Mif and / or CD74. (Item WA3) An inhibitor for improving delivery of chimeric antigen receptor (CAR) T cells, comprising: an inhibitor targeted to Mif and / or CD74; and CAR-T cells comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item WA4) An inhibitor for treating or preventing cancer, comprising: an inhibitor targeted to Mif, an inhibitor targeted to CD74, mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), and optionally a lipid nanoparticle (LNP).(Item WA4) The inhibitor according to any one of the above items, wherein the inhibitor is a protein, polypeptide, oligopeptide, peptide, polynucleotide, oligonucleotide, nucleotide, nucleic acid (including, for example, DNA such as cDNA and genomic DNA, and RNA such as mRNA), polysaccharide, oligosaccharide, lipid, small organic molecule (e.g., hormone, ligand, signaling substance, small organic molecule, molecule synthesized by combinatorial chemistry, small molecule that can be used as a pharmaceutical (e.g., small molecule ligand, etc.)), or a composite molecule thereof. (Item WA5) The inhibitor according to any one of the above items, wherein the inhibitor comprises an antibody or an antibody fragment. (Item WB1) Use of a Mif inhibitor and / or a CD74 inhibitor for producing a medicament for inhibiting tumor immune evasion. (Item WB2) The use according to any one of the above items, wherein the inhibitor suppresses the expression of Mif and / or CD74. (Item WB3) Use for improving delivery of chimeric antigen receptor (CAR) T cells, comprising an inhibitor targeted to Mif and / or CD74, and CAR-T cells comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item WB4) Use for treating or preventing cancer, comprising an inhibitor targeted to Mif, an inhibitor targeted to CD74, mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), and optionally a lipid nanoparticle (LNP). (Item WB4) The use according to any one of the above items, wherein the inhibitor is a protein, polypeptide, oligopeptide, peptide, polynucleotide, oligonucleotide, nucleotide, nucleic acid (including, for example, DNA such as cDNA and genomic DNA, and RNA such as mRNA), polysaccharide, oligosaccharide, lipid, small organic molecule (for example, hormone, ligand, signaling substance, small organic molecule, molecule synthesized by combinatorial chemistry, small molecule that can be used as a pharmaceutical (for example, small molecule ligand, etc.)), or a composite molecule thereof. (Item WB5) The use according to any one of the above items, wherein the inhibitor comprises an antibody or an antibody fragment.(Item WC1) A method for inhibiting tumor immune evasion, comprising administering to a subject an effective amount of a Mif inhibitor and / or a CD74 inhibitor. (Item WC2) The method according to any one of the above items, wherein the inhibitor suppresses expression of Mif and / or CD74. (Item WC3) A method for improving delivery of chimeric antigen receptor (CAR) T cells, comprising an inhibitor targeted to Mif and / or CD74, and mRNA comprising a nucleic acid sequence encoding a CAR. (Item WC4) A method for treating or preventing cancer, comprising an inhibitor targeted to Mif, an inhibitor targeted to CD74, mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), and optionally a lipid nanoparticle (LNP). (Item WC4) The method according to any one of the above items, wherein the inhibitor is a protein, polypeptide, oligopeptide, peptide, polynucleotide, oligonucleotide, nucleotide, nucleic acid (including, for example, DNA such as cDNA and genomic DNA, and RNA such as mRNA), polysaccharide, oligosaccharide, lipid, small organic molecule (for example, hormone, ligand, signaling substance, small organic molecule, molecule synthesized by combinatorial chemistry, small molecule that can be used as a pharmaceutical (for example, small molecule ligand, etc.)), or a composite molecule thereof. (Item WC5) The method according to any one of the above items, wherein the inhibitor comprises an antibody or an antibody fragment.

[0009] <Tumor Microenvironment> (Item V1) A composition for improving the tumor microenvironment, comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item V2) A composition for suppressing tumor growth, comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item V3) A composition for optimizing the immune cell composition of the tumor microenvironment, comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item V4) A composition for promoting immune cell infiltration, comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item VA1) An mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for improving the tumor microenvironment. (Item VA2) An mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for suppressing tumor growth. (Item VA3) An mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for optimizing the immune cell composition of the tumor microenvironment. (Item VA4) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for promoting immune cell infiltration. (Item VB1) Use of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for manufacturing a medicament for improving a tumor microenvironment. (Item VB2) Use of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for manufacturing a medicament for suppressing tumor growth. (Item VB3) Use of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for manufacturing a medicament for optimizing the immune cell composition of a tumor microenvironment. (Item VB4) Use of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for manufacturing a medicament for promoting immune cell infiltration. (Item VC1) A method for improving a tumor microenvironment, comprising administering to a subject an effective amount of a composition comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item VC2) A method for suppressing tumor growth, comprising administering to a subject an effective amount of a composition comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR).(Item VC3) A method for optimizing the immune cell composition of a tumor microenvironment, comprising administering to a subject an effective amount of a composition comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item VC4) A method for promoting immune cell infiltration, comprising administering to a subject an effective amount of a composition comprising mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR). (Item VD) The composition, mRNA, use, or method described in the above items, wherein the mRNA has the characteristics described in any one or more of the above items.

[0010] <Effectiveness Verification> (Item U1) A method for verifying the effect of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), comprising contacting spleen cells with the mRNA and measuring the effect on the spleen cells. (Item U2) A method for evaluating mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), comprising contacting the mRNA with cancer tissue and performing FACS analysis of the cancer tissue. (Item U3) A method for single-cell analysis of the MIF-CD74 axis of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), comprising contacting the mRNA with target cells and analyzing the effect on MIF and CD74 in the cells. (Item U4) A method for evaluating epitope spreading of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), comprising contacting MC38 tumor cells with the mRNA and performing epitope analysis in the tumor cells.

[0011] It is contemplated that the present disclosure may provide one or more of the above-described features in combinations other than those explicitly stated. Still further embodiments and advantages of the present disclosure will be recognized by those skilled in the art upon reading and understanding the following detailed description, if necessary.

[0012] This disclosure demonstrates breakthrough effects in cancer treatment.

[0013] Figure 1 shows a schematic diagram of the engineered FAPCAR-containing LNP. Figure 2 shows the results of an example. The immunogenic tumor microenvironment (TME) attenuated the FAP-targeting activity of CAR-T cells. (A) In vitro binding assay of FAP with lymphocytes transfected with FAPCAR-mRNA. (B) Distribution of CAR-T cells in immunodeficient (NOD / SCID) and immunocompetent (C57BL / 6) cell line-derived allograft models. Luminescence intensity was measured in biologically independent replicates (n = 4). Statistical analysis between each tissue group was performed using one-way analysis of variance (ANOVA) with Tukey's post-hoc test; p < 0.05 was considered significant. Data are presented as mean ± SEM. Figure 3 shows the results of an example. This study was conducted to test efficacy in allograft models derived from colon cancer (MC38), breast cancer (4T1 and E0771), and renal cancer (RENCA) cell lines. (A) Tumor volume was calculated using the longest diameter (L) and shortest diameter (W) as 1 / 2 x L x W. ２ Tumor volume was estimated using the formula: (A) Tumor volume was measured in biologically independent replicates (n = 2 or 3), and statistical analysis between treatment groups was performed using two-way analysis of variance (way-way ANOVA) with Tukey's post-hoc test; p < 0.05 was considered significant. Data are shown as mean ± SEM. (B) Tumor growth in a mouse model of colon cancer treated with different therapeutic combinations. The MC38 cell line was used as the cancer cell. (C) Tumor growth in mouse models of breast cancer and renal cancer treated with different therapeutic combinations. The 4T1 or E0771 cell line was used for breast cancer, and the RENCA cell line was used for renal cancer. Figure 4 shows the involvement of tumor memory in the control of tumor development. (A) Re-challenge in a cured allograft model derived from a colon cancer cell line. (B) Re-challenge in a cured allograft model derived from a breast cancer cell line. Figure 5 shows the induction rate of LNP into memory T cells. CD5 ＋ , CD69 ＋ or CD103 ＋ Transfection rate of LNP into lymphocytes. The transfection rate (Rtrans) was 0.01 for CD5 / 69 / 103 ＋ Among the total population of cells, eGFP-expressing CD5 / 69 / 103 ＋The effector-to-target ratio (EFR) was defined as the percentage of cells in the colon. The results of flow cytometry analysis based on fluorescence intensity are shown. Figure 6 shows a human colorectal cancer (CRC) PDX model. (A) Tumor growth in a colon PDX model treated with different combinations of treatments. LNPs containing FAPCAR-mRNA combined with lymphocytes were intravenously injected twice after transplantation. Tumor growth was measured as described above. Figure 7 shows the relative target killing activity of CAR-T cells. Lactate dehydrogenase (LDH) assays were performed on cocultures of CAR-T cells expressing FAPCAR or GFPCAR with FAP-expressing target cells. The effector-to-target ratios were 3600:1 (S), 36,000:1 (M), and 360,000:1 (L). Relative target killing was expressed as the ratio of FAPCAR-T cell population to GFPCAR-T cell population. Notably, at an effector-to-target ratio of 3600:1, the FAPCAR-T cell group exhibited 46-fold higher target killing compared to the control group. Figure 8 shows the FAPCAR expression test system. (A) Luminescence visualization of FAPCAR-expressing cells after lymphocyte injection of electroporated FAPCAR mRNA or LNPs carrying FAPCAR mRNA. NanoLuc luciferase mRNA was engineered to co-express with FAPCAR mRNA. Lymphocytes carrying the bound mRNA were intravenously administered to model mice. NanoLuc luciferase catalyzes the oxidation of its substrate (furimazine) to produce light, allowing the distribution of FAPCAR-expressing cells to be visualized through luminescence. Figure 9 shows the IC50 curves for 5-FU inhibition on the viability of MC38 cell lines and CDDP inhibition on the viability of B16F10 cell lines. Figure 10 shows an experiment in which the mRNA in LNP was replaced with eGFP mRNA to prove that LNP is not involved in the therapeutic effect. Figure 11 shows an experiment in which Jarrid compounds (CPI455AZO, CPI455NITRO) and a small molecule compound (JB161) were also incorporated. This suggests efficacy. Figure 12 is a schematic diagram of an experiment in which mRNA (transcribed after plasmid cleavage) was eleporated into lymphocytes. Lymphocytes expressing FAPCAR have a significant tendency to accumulate in tumor tissue. They also tend to accumulate in the spleen. Figure 13 shows the results shown in Example 2.A syngenic model of colon cancer (derived from the MC38 cell line) cured with "LNPs + 5-FU + ICIs (anti-mouse PD1 + anti-mouse CTLA)" has been recurrence-free for over 70 days. Figure 14 shows the expansion effect results in Example 7. The left panel shows the results in cancer tissue, indicating clonal convergence. The right panel shows the suggestion of antigen expansion in adipose tissue. When TCR sequence variants were measured in immune cells contained in cancer tissue, clonal variation decreased, indicating that clonal deficiency had been induced. On the other hand, when TCR sequence variants were measured in adipose tissue from the same individual, clonal variation increased, indicating that clonal expansion had been induced. In this way, the CAR-T vector injected into the body first induced designer cells (CAR-T cells) in the spleen and other tissues, and the clones expanded, confirming that memory cells were stored in the body not only in the spleen but also in immune cells in adipocytes. Figure 15 shows the memory function of mRNA CAR-T. Removal was confirmed by CD8a neutralization and CD8b neutralization, which has a different epitope. Tumor progression was observed when CD8 T cells were removed from the circulating blood. The memory function formed by mRNA CAR-T existed as effector T cells in the peripheral blood, and some differentiated into tissue-resident memory T cells (TrM) in the tissue, demonstrating potent effector function. Re-challenge was performed in a curative colon cancer model treated with anti-CD8a and FTY720. Tumors were established again in a syngenic model of colon cancer (derived from the MC38 cell line) that had been cured with "LNPs + 5-FU + ICIs (anti-mouse PD1 + anti-mouse CTLA)" and anti-CD8a (intravenous injection, CD8 from circulating blood) was administered. ＋The mice were injected daily with IgG4-dependent T cell elimination, FTY720 (intraperitoneal injection, to inhibit the migration of mature lymphocytes from the thymus and secondary lymphoid tissues), and PBS. Tumor size was measured using the same method as described above. The reduction in T cells was monitored by FACS. As a result, tumors in mice treated with anti-CD8a showed rapid growth, while tumors in mice treated with FTY720 and PBS showed regression. Figure 16 shows the antitumor effect of mRNA CAR-T in a CDX model. The human pancreatic cancer cell line, MIA PaCa cell line, and FAP-expressing cells (derived from NIH / 3T3 Tet-On® 3G Cell Line) were subcutaneously injected into NOD / SCID mice to establish a cell line-derived xenograft model (CDX model). Ten mice were divided into four groups (n = 2 or 3). Each group received the following treatment regimen via intravenous tail injection every other day for a total of four times. Figure 17 shows a schematic diagram of antigen spread. A strong and durable antitumor effect was demonstrated. Animal testing using mRNA_CAR-T cells carrying an antibody gene against FAP yielded better results than expected. Specifically, 10 C57BL / 6-derived colon cancer MC38 cells were transfected with 100% IgG4-dependent ... ６ + 10 FAP-expressing syngeneic mouse fibroblasts ７ When subcutaneously injected into C57BL / 6 mice, the growth rate reached 150 mm within 7 days. ３The tumors grew to over 100% of the mice, resulting in 100% mortality within approximately three weeks. The mice were then treated with 10 μg of mRNA_CAR-T / LNP (first generation), which targets the FAP of CAFs (rather than cancer cells), administered four times every other day with 5FU (1 mg / kg) plus ICI (10 mg / kg of anti-CTLA4 & anti-PD1), resulting in tumor eradication. The administration of mRNA_CAR-T / LNP (first generation) was essential. The disease-free period of these mice lasted for over 70 days. Subsequent subcutaneous injections of MC38 cancer cells (which lack FAP) failed to result in tumor engraftment. However, rechallenge with cells from another C57BL / 6 mouse-derived breast cancer (4T1, E0771) resulted in tumor growth and tumor death. The tumor implantation sites were similar even at distant sites from the initial tumor site, and were not limited to the local epithelium. Furthermore, we are currently conducting experiments to determine whether tumor engraftment occurs when T cells are removed with a CD8 antibody and tissue-resident memory T cells are inhibited from escaping into the peripheral blood by daily administration of 20 μg of FTY720. This suggests that effector memory T cells are induced by mRNA_CAR-T, resulting in MHC-restricted "epitope expansion" from CAFs to MC38 cells. Conversely, similar results were obtained when breast cancer (4T1, E0771) cells were first transplanted with FAP-expressing syngeneic mouse fibroblasts, followed by MC38 cells, as confirmed in a control experiment. Figure 18 shows the antitumor effect of mRNA_CAR-T in a PDX model. Experiments with PDX showed that treatment with LNPs encapsulating FAPCAR mRNA significantly suppressed tumor growth (Figure 6). DNA was then extracted from tumor tissues from these patients, and Human Markers for Genomic Microsatellite Instability (MSI) was measured, demonstrating microsatellite instability. Figure 19 illustrates the enhanced antitumor effect of methylated m6A-mRNA over conventional mRNA. Compared with group (1) (5-FU + anti-mouse PD1 + anti-mouse CTLA4) and group (4) (PBS), tumors were suppressed in groups (2) and (3) containing LNPs encapsulating FAPCAR mRNA. Among groups (2) and (3), the group (3) in which the mRNA was modified with adenine methylation (m6A) exhibited a stronger antitumor effect.20 shows the effect of methylated mRNA (m6A) CAR-T. As described in Examples 1 and 2, the cell line-derived allograft model was administered to C57BL / 6 mice at a dose of 5×10. ６ Cancer cells (MC38 cell line) and 2.5 × 10 ６The mice were established by subcutaneous injection of a mixture (ratio 2:1) of FAP-expressing cells (prepared from NIH / 3T3 Tet-On® 3G Cell Line). Ten mice were divided into three groups (n = 3 or 4). The following treatment regimens were administered every other day via intravenous tail injection for a total of three times: (1) 5-FU + anti-mouse PD1 + anti-mouse CTLA4, (2) LNPs (containing methylated mRNA) + 5-FU + anti-mouse PD1 + anti-mouse CTLA4. These were used at the following doses: 2 μL of 5-FU (10 mg / mL dissolved in PBS); 10 μL of anti-mouse PD1; 10 μL of anti-mouse CTLA4; the weight of the mRNA in LNPs was 10 μg. (3) PBS. The tumor size was measured using the same method as above. As a result, compared to group (1) (5-FU + anti-mouse PD1 + anti-mouse CTLA4) and group (3) (PBS), group (2) with methylated mRNA-LNP demonstrated early and robust antitumor effects. Figure 21 shows the results of single-cell RNA sequencing (scRNA-seq) of tumor tissue obtained from an MC38 colon cancer mouse model. Tumor tissue was collected from two groups of mice: one group with tumor recurrence after treatment with 5-FU + immune checkpoint inhibitor (ICI) + LNP, and the other group without treatment. Experimental method: Single-cell suspensions were prepared from tumor tissue and single-cell RNA sequencing was performed using the 10x Genomics Chromium platform. Sequencing data underwent initial processing using the Cell Ranger pipeline (including demultiplexing, genome alignment, and generation of a feature barcode matrix). Subsequent bioinformatics analysis (including quality control, normalization, data integration, and visualization) was performed using Seurat and related R packages.Experimental Results: Single-cell analysis demonstrated that immune cells within the tumor microenvironment (TME) were predominantly monocyte / macrophage lineage, with only a few T and B cells detected, and only a small number of NKT cells observed. Expression analysis of Mif and CD74 revealed distinct expression patterns within the TME. This experiment aimed to evaluate the specific cytotoxicity of spleen-derived lymphocytes against MC38 cells in MC38 tumor-bearing mice treated with m6A-LNP (a combination of 5-FU and immune checkpoint inhibitors). Results showed that spleen lymphocytes from MC38 tumor-bearing mice treated with m6A-LNP exhibited significantly enhanced cytotoxicity specifically against MC38 cells, indicating epitope spreading due to the treatment. This observation highlights the therapeutic benefits of epitope spreading induced by m6A-LNP treatment. Figure 22 shows the results of single-cell RNA sequencing (scRNA-seq) of tumor tissue obtained from the MC38 colon cancer mouse model. Tumor tissue was collected from two groups of mice: one group with tumor recurrence after treatment with 5-FU + immune checkpoint inhibitor (ICI) + LNP, and the other group without treatment. Experimental Method: Single-cell suspensions were prepared from tumor tissue and single-cell RNA sequencing was performed using the 10x Genomics Chromium platform. Sequencing data underwent initial processing using the Cell Ranger pipeline (including demultiplexing, genome alignment, and generation of a feature barcode matrix). Subsequent bioinformatics analysis (including quality control, normalization, data integration, and visualization) was performed using Seurat and related R packages. Experimental Results: Single-cell analysis showed that immune cells within the tumor microenvironment (TME) were predominantly of the monocyte / macrophage lineage, with only a few T and B cells detected, and only a small number of NKT cells were observed. Expression analysis of Mif and CD74 revealed distinct expression patterns within the TME.Figure 22 shows single-cell RNA sequencing (scRNA-seq) analysis performed on tumor tissues obtained from two groups of MC38 colorectal cancer mouse models. One group consisted of mice with tumors that recurred after treatment with a regimen of 5-FU, ICI, and LNPs, while the other group consisted of untreated tumor-bearing mice. Specifically, we focused on the expression pattern of the Mif-CD74 signaling axis to assess its possible involvement in tumor recurrence and immune evasion. The immune cell composition within the tumor microenvironment (TME) was predominantly monocyte / macrophage lineage cells, with only a few T cells and B cells, and only a small number of NKT cells. This immune profile suggests that the tumor microenvironment may promote tumor progression and immune evasion, potentially enhancing tumor aggressiveness and therapy resistance. Furthermore, the unique expression patterns of Mif and CD74 in the TME suggest that this signaling pathway may play an important role in regulating immunosuppression associated with tumor recurrence and therapy resistance. Figure 23 shows the analysis of intercellular communication patterns based on the above-mentioned single-cell RNA sequencing (scRNA-seq) data using CellChat. Specifically, we focused on the MIF-CD74 signaling pathway. Results: CellChat analysis revealed significantly elevated expression levels of macrophage migration inhibitory factor (MIF) and CD74 in tumor tissues. Tumor-associated cell clusters (clusters 0, 2-7, and 10) showed significant outward transmission of MIF signals. Meanwhile, monocyte / macrophage clusters (clusters 1 and 11) were identified as the primary recipients of these signals. Figure 23 shows the intercellular communication patterns of the MIF-CD74 signaling pathway analyzed using CellChat based on the above-mentioned scRNA-seq data. The analysis results showed significantly elevated expression levels of macrophage migration inhibitory factor (MIF) and CD74 in the analyzed tumor tissues.Clusters of tumor-associated cells (clusters 0, 2-7, and 10) emitted prominent MIF signals, while clusters of monocytes / macrophages (clusters 1 and 11) were the primary recipients of these signals. This communication pattern is consistent with previous reports of MIF-CD74 interactions between tumor cells and macrophages and further suggests that this signaling pathway plays an important role in promoting immune evasion and tumor progression. Figure 24 shows the effect of therapeutic introduction of anti-CD74 and anti-MIF antibodies on tumor growth inhibition in an MC38 tumor-bearing mouse model, with the aim of evaluating the therapeutic efficacy of blocking the CD74-MIF signaling axis. Experimental Methods: MC38 tumor-bearing mice were divided into five treatment groups. (1) m6A-LNP + 5-FU + anti-mouse PD1 + anti-mouse CTLA4, (2) m6A-LNP + 5-FU + anti-mouse PD1 + anti-mouse CTLA4 + anti-MIF (5 μg / 25 g), (3) m6A-LNP + 5-FU + anti-mouse PD1 + anti-mouse CTLA4 + anti-CD74 (5 μg / 25 g), (4) m6A-LNP + 5-FU + anti-mouse PD1 + anti-mouse CTLA4 + anti-mouse MIF (5 μg / 25 g) + anti-CD74 (5 μg / 25 g), and (5) PBS as a control. Results: Combination therapy with anti-CD74 and / or anti-MIF antibodies (m6A-LNP + 5-FU + anti-PD1 + anti-CTLA4) significantly suppressed tumor growth compared to the control group (***p<0.0001). Figure 24 shows the effect of incorporating anti-CD74 and anti-MIF antibodies into the treatment regimen on tumor growth inhibition in an MC38 tumor-bearing mouse model to evaluate the therapeutic efficacy of blocking the CD74-MIF signaling axis. The results showed that adding anti-CD74 or anti-MIF antibodies to the combination therapy of m6A-LNP, 5-FU, and immune checkpoint inhibitors (anti-PD1 and anti-CTLA4) significantly suppressed tumor growth and effectively enhanced the antitumor effect. These findings indicate that blocking the MIF-CD74 signaling pathway plays a beneficial role in cancer treatment. Figure 25 shows the biodistribution of polybetaine-optimized lipid nanoparticles (LNPs) in a mouse model of colon cancer.Experimental method: LNPs encapsulating eGFP mRNA were intravenously administered to colorectal cancer-bearing mice. 24 hours later, cells collected from the mouse spleen, liver, and tumor tissue were incubated with phycoerythrin (PE)-labeled anti-CD5 antibody (BioLegend, catalog number 100607) and analyzed by fluorescence-activated cell sorting (FACS). Results: FACS analysis showed that PolyBetaine-LNPs inhibited CD5-positive (CD5. ＋ ) cells compared to conventional PEG-based LNPs. Meanwhile, accumulation in hepatocytes was significantly reduced. This figure shows the biodistribution of polybetaine-optimized lipid nanoparticles (LNPs) in a mouse model of colorectal cancer, with the aim of assessing accumulation in tumor tissue. FACS analysis revealed that PolyBetaine-LNPs significantly reduced liver accumulation compared to conventional PEG-based LNPs, while significantly increased CD5-positive (CD5) cells in tumor tissue. ＋) cells. These results suggest that PolyBetaine-optimized LNPs have superior tissue specificity, potentially enhancing therapeutic efficacy and minimizing off-target effects in non-target tissues such as the liver. Figure 26 shows the effect of combining polybetaine-optimized liposomal nanoparticles (PolyBetaine-LNPs) with 5-FU and immune checkpoint inhibitors (anti-PD-1 and anti-CTLA4) on tumor growth in a mouse model of colorectal cancer. Experimental Method: MC38 colorectal cancer mouse models were intravenously administered the following every other day (a total of four times): (1) LNP + 5-FU + anti-PD-1 + anti-CTLA4, (2) PolyBetaine-LNP (N / P = 6) + 5-FU + anti-PD-1 + anti-CTLA4, (3) PolyBetaine-LNP (N / P = 9) + 5-FU + anti-PD-1 + anti-CTLA4, and (4) PBS as a control. Results: Combination treatment of PolyBetaine-LNPs (both N / P = 6 and N / P = 9) with 5-FU and immune checkpoint inhibitors not only significantly suppressed tumor growth compared to the PBS control (***p<0.0001), but also showed a slightly stronger tumor-inhibitory effect than the conventional LNP treatment group. Figure 26 shows the inhibitory effect of polybetaine-optimized liposomes (PolyBetaine-LNPs) in combination with 5-FU and immune checkpoint inhibitors (anti-PD1 and anti-CTLA4) on tumor growth in a mouse model of colorectal cancer. The results showed that therapeutic formulations containing PolyBetaine-LNPs effectively inhibited tumor growth and demonstrated favorable therapeutic efficacy and stability. These results suggest that the optimization strategy for PolyBetaine may enhance the antitumor therapeutic efficacy of lipid nanoparticles. Figure 27 shows the results of evaluating the combined effect of CAR-T therapy (m6A-modified LNPs) and an inhibitor targeting RNA demethylase (FTO-i) in a mouse model of colon cancer (MC38). The addition of FTO-i significantly enhanced the antitumor efficacy of CAR-T cells and effectively inhibited tumor growth.These findings demonstrate that, although there are numerous types of RNA methylation (more than 120 types have been identified to date), selective inhibition of RNA demethylation pathways, such as FTO, can effectively improve the therapeutic efficacy of CAR-T cells. This highlights the promising potential of applying RNA modification strategies to optimize CAR-T cell therapy. Figures 28-31 show the therapeutic effects of CAR-T cells targeting cancer stem cell (CSC) markers (EpCAM, LGR5, CD133, and Her2 / neu) in combination with 5-FU and immune checkpoint inhibitors (anti-PD-1 and anti-CTLA4) in the MC38 mouse model of colorectal cancer. The results showed that CAR-T cells targeting EpCAM, LGR5, and CD133 effectively suppressed tumor growth compared to the control group treated with 5-FU and immune checkpoint inhibitors alone. The EpCAM-CAR-T cell and LGR5-CAR-T cell groups showed the most significant antitumor effects. Meanwhile, Her2 / neu-CAR-T cells showed relatively limited efficacy. These findings are consistent with existing knowledge that EpCAM, LGR5, and CD133 are widely recognized as CSC markers for colorectal cancer, while Her2 / neu is not generally recognized as a CSC marker for colorectal cancer. Therefore, targeting CSC surface markers via CAR-T cells shows promising potential as an effective antitumor therapeutic strategy. Figure 29 shows the therapeutic effects of CAR-T cells targeting cancer stem cell (CSC) markers (EpCAM, LGR5, CD133, and Her2 / neu) in combination with 5-FU and immune checkpoint inhibitors (anti-PD-1 and anti-CTLA4) in the MC38 mouse model of colorectal cancer. The results showed that CAR-T cells targeting EpCAM, LGR5, and CD133 effectively suppressed tumor growth compared to a control group administered only 5-FU and immune checkpoint inhibitors. The EpCAM-CAR-T cell and LGR5-CAR-T cell groups showed the most significant antitumor effects, while Her2 / neu-CAR-T cells showed relatively limited efficacy.These findings are consistent with existing knowledge that EpCAM, LGR5, and CD133 are widely recognized as CSC markers in colorectal cancer, whereas Her2 / neu is not generally recognized as a CSC marker in colorectal cancer. Therefore, targeting CSC surface markers via CAR-T cells shows promising potential as an effective antitumor therapeutic strategy.

[0014] Throughout this specification, singular expressions should be understood to include the plural concept unless otherwise specified. Thus, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept unless otherwise specified. Furthermore, it should be understood that terms used in this specification are used in the sense commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In case of conflict, the present specification (including definitions) will prevail.

[0015] (Definitions) We first explain the terms and general techniques used in this disclosure.

[0016] The following provides definitions of terms particularly used in this specification and / or explains basic technical content as appropriate.

[0017] As used herein, "about" means ±10% of the numerical value that follows. For example, "about 20" includes "18 to 22." Numerical ranges include all values ​​between and at the endpoints. When "about" refers to a range, it applies to both endpoints of the range. Thus, for example, "about 20 to 30" includes "18 to 33."

[0018] In this specification, when a gene name and its product are written in all capital letters, contrary to the usual usage, it may refer to both the gene and the protein. For example, the FOXP3 gene and the FOXP3 protein may be used interchangeably, and the term FoxP3 refers to both the concept and entity (whole) of the gene or protein.

[0019] As used herein, the term "T cell" is used in the broad sense used in the art and refers to lymphocytes produced in the bone marrow that migrate to the thymus and mature. T cells may be CD45-positive and CD3-positive cells among normal fractions of peripheral blood and bone marrow-derived mononuclear cells. T cells used may be, but are not limited to, T cells isolated from a donor, particularly a human donor. Examples of T cells and cells derived therefrom include isolated T cells that have not been passaged in culture, T cells that have been passaged and maintained under cell culture conditions without immortalization, and immortalized T cells that can be maintained indefinitely under cell culture conditions. It is known that there are multiple types of T cells based on their functions, including effector memory T cells (Teff), naive T cells (Tnv), stem cell memory T cells (Tscm), central memory T cells (Tcm), and terminally differentiated RA-positive T cells (Temra). As used herein, "peripheral T cells" refers to T cells present outside the thymus, and can be obtained from peripheral blood, lymph nodes, and other tissues. The term "peripheral T cells" as used herein simply refers to a cell population containing peripheral T cells, and does not require that the T cells be isolated. Cell fractions containing various lymphocytes other than T cells, such as peripheral blood mononuclear cells (PBMCs), may also be used.

[0020] As used herein, a "cell population" refers to a population containing two or more cells, and may be, for example, a collection of cells gathered in a planar manner, or a cell mass formed by cells adhering to each other in a three-dimensional manner. Furthermore, a "cell population" may be formed by a single type of cell, or may contain multiple types of cells. When referring to a cell population of T cells of the present disclosure, it is sufficient that the cell population contains at least one cell that can have effector function in the location where it is to function (typically in the body), such as Tnv, Tscm, Tcm, or Tempra.

[0021] As used herein, "flow cytometry" refers to a technique for measuring the number of cells, solids, and other biological particles suspended in a liquid, as well as their individual physical, chemical, and biological properties. A device using this technique is called a "flow cytometer." In this disclosure, the "positive" and "negative" status of a cell marker (e.g., FoxP3, etc.) is determined by flow cytometry, as commonly used in the art. More specifically, in flow cytometry, cells are lined up and flowed, and the number of cells is counted using spectroscopic techniques. For example, cells labeled with fluorescent or luminescent enzymes are irradiated with laser light, and the resulting fluorescent or luminescent signals are detected by a detector such as a photodiode, thereby counting the number of target cells. Furthermore, the detection results from the detector can be input into a computer and displayed as a two-dimensional plot. This allows for easy identification of the presence and number of target cells.

[0022] As used herein, the term "chimeric antigen receptor (CAR)" refers to an engineered receptor that can confer antigen specificity to cells (e.g., immune cells such as T cells). CARs are also known as artificial T cell receptors, chimeric T cell receptors, or chimeric immune receptors. A CAR is an engineered receptor that transfers antigen specificity to immune system cells (e.g., T cells such as naive T cells, central memory T cells, effector memory T cells, or a combination thereof, NK cells, macrophages, etc.). CARs may comprise, for example, an antigen-specific targeting region, an extracellular domain, a transmembrane domain, a costimulatory domain, and / or an intracellular signaling domain. They may also include bispecific CARs that use multiple (usually two types) antigen-specific targeting regions. Preferably, the CAR of the present disclosure comprises at least one extracellular domain capable of binding to an antigen, at least one transmembrane domain, and at least one intracellular domain. When used in combination with T cells, the term "CAR-T cells" may be used. CARs that can be used include first-generation, second-generation, and third-generation CARs. Here, a "first-generation CAR" refers to a combination of a tandemly linked VH chain and VL chain of a monoclonal antibody variable region specific to a tumor-associated antigen (scFv) and a T cell receptor ζ chain. A "second-generation CAR" refers to a first-generation CAR that incorporates one costimulatory factor, such as CD28 (associated with PI3K) or 4-1BB (associated with TRAFs), which is considered to be important for T cell activation. A "third-generation CAR" refers to a first-generation CAR that incorporates multiple costimulatory factors, such as CD28 (associated with PI3K) or 4-1BB (associated with TRAFs), which are considered to be important for T cell activation.

[0023] Chimeric antigen receptors (CARs) are artificially constructed hybrid proteins or polypeptides containing the antigen-binding domain of an antibody (e.g., a single-chain variable fragment (scFv)) linked to a T cell signaling domain via a transmembrane domain. CARs feature MHC-independent antigen binding properties of monoclonal antibodies to redirect T cell specificity and reactivity toward selected targets. MHC-independent antigen recognition can confer the ability of CAR-expressing T cells or T cells in a cell population to recognize antigens independently of antigen processing, allowing tumor immune escape.

[0024] The intracellular T cell signaling domain of a CAR can include, for example, a T cell receptor signaling domain, a T cell costimulatory signaling domain, or both. The T cell receptor signaling domain refers to a portion of a CAR that includes the intracellular domain of a T cell receptor, such as the intracellular portion of the CD3 zeta protein. The costimulatory signaling domain refers to a portion of a CAR that includes the intracellular domain of a costimulatory molecule, which is a cell surface molecule other than an antigen receptor or its ligand, that is required for an efficient lymphocyte response to an antigen.

[0025] As used herein, the term "extracellular domain of" refers to the extracellular domain of an antibody against a substance of interest (such as an antigen). Non-limiting examples include scFv, VH, and VL regions.

[0026] As used herein, the terms "drug," "agent," or "factor" (all of which correspond to the English term "agent") are used interchangeably in a broad sense and may refer to any substance or other element (e.g., energy such as light, radioactivity, heat, or electricity) that can achieve the intended purpose. Examples of such substances include, but are not limited to, proteins, polypeptides, oligopeptides, peptides, polynucleotides, oligonucleotides, nucleotides, nucleic acids (e.g., DNA such as cDNA and genomic DNA, and RNA such as mRNA), polysaccharides, oligosaccharides, lipids, small organic molecules (e.g., hormones, ligands, signaling substances, small organic molecules, molecules synthesized by combinatorial chemistry, small molecules that can be used as pharmaceuticals (e.g., small molecule ligands), etc.), and composite molecules thereof. Typical examples of factors specific to a polynucleotide include, but are not limited to, polynucleotides that have a certain degree of sequence homology (e.g., 70% or more sequence identity) with respect to the sequence of the polynucleotide, and polypeptides such as transcription factors that bind to promoter regions. Typical examples of factors specific to a polypeptide include, but are not limited to, antibodies or derivatives or analogs thereof (e.g., single-chain antibodies) specifically directed against the polypeptide, specific ligands or receptors when the polypeptide is a receptor or ligand, and substrates when the polypeptide is an enzyme.

[0027] As used herein, the terms "small molecule" or "small molecule agent" refer to a molecule having a relatively low molecular weight, whether naturally occurring or artificially created (e.g., by chemical synthesis). Typically, a small molecule is an organic compound (i.e., it contains carbon). A small molecule may contain multiple carbon-carbon bonds, stereocenters, and other functional groups (e.g., amines, hydroxyls, carbonyls, heterocycles, and the like). In certain embodiments, the molecular weight of a small molecule is about 1,000 g / mol or less, about 900 g / mol or less, about 800 g / mol or less, about 700 g / mol or less, about 600 g / mol or less, about 500 g / mol or less, about 400 g / mol or less, about 300 g / mol or less, about 200 g / mol, or about 100 g / mol or less. In certain embodiments, the molecular weight of the small molecule is at least about 100 g / mol, at least about 200 g / mol, at least about 300 g / mol, at least about 400 g / mol, at least about 500 g / mol, at least about 600 g / mol, at least about 700 g / mol, at least about 800 g / mol, or at least about 900 g / mol, or at least about 1,000 g / mol. Combinations of the above ranges are also possible (e.g., at least about 200 g / mol and up to about 500 g / mol). In certain embodiments, the small molecule is a therapeutically active agent such as a drug (e.g., a molecule approved by the U.S. Food and Drug Administration as listed in the U.S. Code of Federal Regulations (C.F.R.)). The small molecule may be complexed with one or more metal atoms and / or metal ions. In this example, the small molecule is also referred to as an "organometallic small molecule." Preferred small molecules are biologically active in that they produce a biological effect in animals, preferably mammals, and more preferably humans. Small molecules include, but are not limited to, radionuclides and imaging agents. In certain embodiments, the small molecule is a drug. Preferably, but not necessarily, the drug has already been deemed safe and effective for use in humans or animals by the appropriate government or regulatory agency.For example, drugs approved for human use are listed by the FDA under 21 C.F.R. §§ 330.5, 331-361, and 440-460, which are incorporated herein by reference, and drugs for veterinary use are listed by the FDA under 21 C.F.R. §§ 500-589, which are incorporated herein by reference. All listed drugs are considered acceptable for use according to the present disclosure.

[0028] As used herein, the term "inhibitor" refers to an agent whose presence or level correlates with a decrease in the level or activity of a modulated target. In some embodiments, an inhibitor may act directly (e.g., by binding to the target, directly exerting an effect on the target). In some embodiments, an inhibitor may act indirectly (e.g., by interacting with and / or otherwise altering a modulator of the target such that the level and / or activity of the target is reduced). In some embodiments, an inhibitor correlates with a target level or activity whose presence or level is reduced compared to a particular reference level or activity (e.g., observed under appropriate reference conditions, such as in the presence of a known inhibitor or in the absence of an inhibitor disclosed herein). The terms "inhibition" or "inhibiting" are not limited to complete inhibition. Thus, in some embodiments, partial inhibition or a relative reduction is included within the scope of the term "inhibition." For example, in the context of risk and / or incidence of tumor recurrence and / or metastasis, the term, in some embodiments, refers to a reduction in the risk or incidence of tumor recurrence and / or metastasis to a level that is reproducibly and / or statistically significantly lower than an initial level or other suitable reference level, which may be, for example, a baseline level of risk or incidence of tumor recurrence and / or metastasis in the absence of or prior to administration of a composition described herein. In some embodiments, the term refers to a reduction in the risk or incidence of tumor recurrence and / or metastasis to a level that is less than 75%, less than 50%, less than 40%, less than 30%, less than 25%, less than 20%, less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, less than 0.1%, less than 0.01%, less than 0.001%, or less than 0.0001% of an initial level, which may be, for example, a baseline level of risk or incidence of tumor recurrence and / or metastasis in the absence of or prior to administration of a composition described herein.

[0029] As used herein, "modification" in relation to a gene (nucleic acid, protein, etc.) refers to inserting a base sequence of a nucleic acid in a cell, changing a base sequence of a nucleic acid, deleting a portion of a base sequence of a nucleic acid in a cell, or a combination thereof.

[0030] As used herein, the term "disease" is broadly interpreted to refer to a state of mental or physical discomfort or inconvenience in humans or animals, and refers to any condition that cannot be described as a healthy state, such as illness, disability, or various symptoms, which are not specifically defined. Diseases that may be the subject of the present disclosure include, but are not limited to, diseases in which an immune response may be associated, such as cancer, autoimmune diseases, allergies, and infectious diseases.

[0031] As used herein, the term "cancer" refers to a malignant neoplasm (Stedman's Medical Dictionary, 25th ed.; Hensyl ed.; Williams & Wilkins: Philadelphia, 1990). Of particular interest in the context of some embodiments of the present disclosure are cancers that are treated by cell-killing and / or ablative therapy (e.g., surgical resection and / or certain chemotherapeutic drug therapy, such as cytotoxic therapy). In some embodiments, cancers treated in accordance with the present disclosure are surgically resected (i.e., at least one tumor has been surgically removed). In some embodiments, cancers treated in accordance with the present disclosure are those for which resection is the standard of care. In some embodiments, cancers treated in accordance with the present disclosure are those that have metastasized. In certain embodiments, exemplary cancers include acoustic neuroma; adenocarcinoma; adrenal carcinoma; anal cancer; angiosarcoma (e.g., lymphangiosarcoma, lymphangioendothelial sarcoma, angiosarcoma); appendix cancer; benign monoclonal gammopathy; biliary tract cancer (e.g., cholangiocarcinoma); bile duct carcinoma; bladder cancer; bone cancer; breast cancer (e.g., adenocarcinoma of the breast, papillary carcinoma of the breast, breast carcinoma, medullary carcinoma of the breast); brain cancer (e.g., meningioma, glioblastoma, glioma (e.g., astrocytoma, oligodendroglioma), medulloblastoma); bronchial carcinoma; carcinoid tumor; cardiac tumor; cervical cancer (e.g., cervical adenocarcinoma); choriocarcinoma; chordoma; craniopharyngioma; colorectal cancer (e.g., colon cancer, rectal cancer, colorectal cancer, adenocarcinoma); connective tissue cancer; epithelial carcinoma; intraductal carcinoma in situ; ependymoma; endothelial sarcoma (e.g., Kaposi's sarcoma, multiple idiopathic hemorrhagic sarcoma); endometrial cancer (e.g., uterine carcinoma, uterine sarcoma); esophageal cancer (e.g., esophageal adenocarcinoma, Barrett's adenocarcinoma); Ewing's sarcoma; eye cancer (e.g., intraocular melanoma, retinoblastoma); familial hypereosinophilia; gallbladder cancer; gastric cancer (e.g., gastric adenocarcinoma); gastrointestinal stromal tumor (GIST); germ cell carcinoma; head and neck cancer (e.g., head and neck squamous cell carcinoma), oral cancer (e.g., oral squamous cell carcinoma), throat cancer (e.g., laryngeal carcinoma, pharyngeal carcinoma, nasopharyngeal carcinoma, oropharyngeal carcinoma);Hematopoietic cancers (e.g., leukemias, e.g., acute lymphocytic leukemia (ALL) (e.g., B-cell ALL, T-cell ALL), acute myeloid leukemia (AML) (e.g., B-cell AML, T-cell AML), chronic myeloid leukemia (CML) (e.g., B-cell CML, T-cell CML), and chronic lymphocytic leukemia (CLL) (e.g., B-cell CLL, T-cell CLL)); lymphomas, e.g., Hodgkin's lymphoma (HL) (e.g., B-cell HL, T-cell HL) and non-Hodgkin's lymphoma (NHL) (e.g., B-cell NHL, e.g., diffuse large cell lymphoma, lymphoma (DLCL) (e.g., diffuse large B-cell lymphoma), follicular lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), mantle cell lymphoma (MCL), marginal zone B-cell lymphoma (e.g., mucosa-associated lymphoid tissue (MALT) lymphoma, nodal marginal zone B-cell lymphoma, splenic marginal zone B-cell lymphoma), primary mediastinal B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma (i.e., Waldenstrom's macroglobulinemia), hairy cell leukemia (HCL), immunoblastic large cell lymphoma (IMLL), lymphoma, precursor B-lymphoblastic lymphoma, and primary central nervous system (CNS) lymphoma; and T-cell NHL, e.g., precursor T-lymphoblastic lymphoma / leukemia, peripheral T-cell lymphoma (PTCL) (e.g., cutaneous T-cell lymphoma (CTCL) (e.g., mycosis fungoides, Sézary syndrome), angioimmunoblastic T-cell lymphoma, extranodal natural killer T-cell lymphoma, enteropathy-type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, and anaplastic large cell lymphoma); combinations of one or more leukemias / lymphomas as above; multiple myeloma; heavy chain disease (e.g., Hemangioblastoma; histiocytosis; hypopharyngeal carcinoma; inflammatory myofibroblastic tumor; immune cell amyloidosis; kidney cancer (e.g., nephroblastoma (also known as Wilms' tumor), renal cell carcinoma); liver cancer (e.g., hepatocellular carcinoma (HCC), malignant hepatoma); lung cancer (e.g., bronchogenic carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), adenocarcinoma of the lung); leiomyosarcoma (LMS); mastocytosis (e.g., systemic mastocytosis); melanoma; midline carcinoma; multiple endocrine neoplasia syndrome; muscle carcinoma; myelodysplastic syndrome (MDS); mesothelioma;Myeloproliferative disorders (MPDs) (e.g., polycythemia vera (PV), essential thrombocythemia (ET), myeloid metaplasia of unknown etiology (AMM) (also known as myelofibrosis (MF)), chronic idiopathic myelofibrosis, chronic myelogenous leukemia (CML), chronic neutrophilic leukemia (CNL), hypereosinophilic syndrome (HES)); nasopharyngeal carcinoma; neuroblastoma; neurofibroma (e.g., type 1 or type 2 neurofibromatosis (NF), schwannomatosis) ; neuroendocrine cancer (e.g., gastrointestinal pancreatic neuroendocrine tumor (GEP-NET), carcinoid tumor); osteosarcoma (e.g., bone cancer); ovarian cancer (e.g., cystadenocarcinoma, ovarian embryonal carcinoma, ovarian adenocarcinoma); papillary adenocarcinoma; pancreatic cancer (e.g., pancreatic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), pancreatic islet cell tumor); parathyroid carcinoma; papillary adenocarcinoma; penile cancer (e.g., Paget's disease of the penis and scrotum); pharyngeal cancer; pinealoma; Pituitary cancer; pleuropulmonary blastoma; primitive neuroectodermal tumor (PNT); plasma cell neoplasm; paraneoplastic syndrome; intraepithelial neoplasia; prostate cancer (e.g., prostatic adenocarcinoma); rectal cancer; rhabdomyosarcoma; retinoblastoma; salivary gland cancer; skin cancer (e.g., squamous cell carcinoma (SCC), keratoacanthoma (KA), melanoma, basal cell carcinoma (BCC)); small intestine cancer (e.g., appendix cancer); soft tissue sarcoma (e.g., malignant fibrous histiocytoma (MF) H), liposarcoma, malignant peripheral nerve sheath tumor (MPNST), chondrosarcoma, fibrosarcoma, myxosarcoma); sebaceous gland carcinoma; gastric cancer; small intestine cancer; sweat gland carcinoma; synovial tumor; testicular cancer (e.g., seminoma, testicular embryonal carcinoma); thymic carcinoma; thyroid cancer (e.g., papillary thyroid carcinoma, papillary thyroid carcinoma (PTC), medullary thyroid carcinoma); urethral cancer; uterine cancer; vaginal cancer; and vulvar cancer (e.g., Paget's disease of the vulva);

[0032] As used herein, a subject having an "immune response" to a certain component or substance means that some kind of immune reaction occurs against the component or substance. The component or substance can be identified by observing changes in various immune cells or increases or decreases in immune-related substances (e.g., FAP, cytokines, etc.) in the subject or biological components (e.g., cells, etc.) derived from the subject, and the determination can be made using objective indicators or by subjective judgment based on the experience of a physician or other person.

[0033] "Subjects" contemplated herein include, but are not limited to, humans (i.e., males or females of any age group, e.g., pediatric subjects (e.g., infants, children, adolescents) or adult subjects (e.g., young adults, middle-aged adults, or elderly adults)) and / or non-human animals, e.g., mammals (e.g., primates (e.g., cynomolgus monkeys, rhesus monkeys); domestic animals, e.g., cows, pigs, horses, sheep, goats, cats, and / or dogs; and / or birds (e.g., chickens, ducks, geese, and / or turkeys)). In certain embodiments, the animal is a mammal (e.g., at any stage of development). In some embodiments, the animal (e.g., non-human animal) can be a transgenic or genetically engineered animal. In some embodiments, the subject is a tumor resection subject, e.g., a subject that has recently undergone tumor resection. In some embodiments, the tumor resection subject is a subject who underwent tumor resection less than 72 hours (including, for example, less than 48 hours, less than 24 hours, less than 12 hours, less than 6 hours, or less) before being administered a composition described herein. In some embodiments, the tumor resection subject is a subject who underwent tumor resection less than 48 hours before being administered a composition described herein. In some embodiments, the tumor resection subject is a subject who underwent tumor resection less than 24 hours before being administered a composition described herein. In some embodiments, the tumor resection subject is a subject who underwent tumor resection less than 12 hours before being administered a composition described herein.

[0034] In one embodiment, the disease to be treated by the method of the present disclosure may be a human patient suffering from cancer, such as carcinoma, lymphoma, sarcoma, blastoma, and leukemia. Exemplary target cancers include, but are not limited to, cancers of B-cell origin, breast cancer, gastric cancer, neuroblastoma, osteosarcoma, lung cancer, skin cancer, prostate cancer, colon cancer, renal cell carcinoma, ovarian cancer, rhabdomyosarcoma, leukemia, mesothelioma, pancreatic cancer, head and neck cancer, retinoblastoma, glioma, glioblastoma, liver cancer, and thyroid cancer.

[0035] As used herein, the term "substantially" refers to a qualitative state of exhibiting a characteristic or property of interest to a complete or nearly complete extent or degree. Those skilled in the art will understand that an agent of interest will achieve or avoid, if at all, an absolute result; for example, an agent of interest will have virtually no effect on the immune response, e.g., inflammation. Thus, the term "substantially" is used herein to express the potential lack of absoluteness inherent in many biological and chemical effects.

[0036] As used herein, the terms "treatment," "treat," and "treating" refer to reversing, alleviating, delaying the onset of, or inhibiting the progression of a "condition" (e.g., a disease, disorder, or condition, including one or more signs or symptoms thereof), as described herein, e.g., a cancer or tumor. In some embodiments, treatment may be administered after one or more signs or symptoms have developed or are observed. Treatment may be continued after symptoms have resolved, e.g., to delay or prevent recurrence and / or spread.

[0037] As used herein, a "therapeutically effective amount" is an amount sufficient to provide a therapeutic effect in treating a condition, which may be or may include, for example, a reduction in frequency and / or severity and / or a delay in the onset of one or more features or symptoms associated with the condition. A therapeutically effective amount refers to an amount of a therapeutic agent(s) alone or in combination with other therapies that provides a therapeutic effect in treating a condition. The term "therapeutically effective amount" may encompass an amount that improves overall treatment, reduces or avoids the symptoms or causes of a condition, or enhances the therapeutic effectiveness of another therapeutic agent. Those skilled in the art will understand that a therapeutically effective amount need not be contained in a single dosage form. Rather, administration of an effective amount may require multiple administrations, optionally over time (e.g., according to a dosing regimen). A "therapeutically effective amount" may also be abbreviated to "effective amount." A "prophylactically effective amount" is an amount sufficient to prevent a condition (e.g., significantly delay the onset or recurrence of one or more symptoms or characteristics of a condition, e.g., so that it / they are not detected at a time that would be expected in the absence of administration of that amount). A prophylactically effective amount of a composition refers to an amount of a therapeutic agent(s), alone or in combination with other agents, that provides a prophylactic benefit in preventing a condition. As used herein, "prevention" refers to significantly delaying the onset or recurrence of one or more symptoms or characteristics of a condition, e.g., so that it / they are not detectable at a time point that would be expected in the absence of administration of that amount. The term "prophylactically effective amount" can encompass an amount that improves overall prevention or enhances the prophylactic efficacy of another prophylactic agent. Those skilled in the art will understand that a prophylactically effective amount need not be contained in a single dosage form. Rather, administration of an effective amount may require multiple administrations, optionally over time (e.g., according to a dosing regimen).

[0038] As used herein, "FAP (fibroblast-activation protein)" is an abbreviation for fibroblast activation protein, and refers to a type of serine protease localized in the cell membrane. FAP exists as a dimeric membrane-bound glycoprotein and is characterized by peptidase activity. This protein is highly expressed primarily in cancer-associated fibroblasts (CAFs) and fibroblasts undergoing wound healing, while it is hardly expressed in normal, quiescent fibroblasts. For this reason, FAP is recognized as an important molecule involved in the pathological progression of cancer tissues and fibrotic diseases. In humans, FAP corresponds to gene number GeneID: 2191 and is encoded by the FAP gene located on chromosome 7, 7q22.1. This protein has a molecular weight of approximately 88 kDa and is structurally similar to DPPIV (Dipeptidyl peptidase IV, CD26). However, FAP is known to possess both dipeptidase and gelatinase activities. FAP is primarily involved in extracellular matrix (ECM) remodeling, particularly its ability to degrade collagen and gelatin. As a result, it promotes cancer cell proliferation and invasion in the tumor microenvironment (TME) and contributes to tissue repair during wound healing. Furthermore, high FAP expression has been observed in fibrotic diseases such as liver cirrhosis and pulmonary fibrosis, suggesting its involvement in the progression of these conditions. Taking advantage of the specific expression characteristics of FAP, its application as a target molecule in cancer therapy has been promoted in recent years. For example, FAP-targeted antibody-drug conjugates (ADCs) and FAP-specific CAR-T cell therapies have been developed, demonstrating the potential for novel immunotherapy against FAP-expressing tumors. In addition, attempts are underway to visualize FAP expression by PET imaging using a radiolabeled FAP ligand (FAPI) to improve the accuracy of cancer diagnosis. Furthermore, inhibition of FAP is thought to be effective as a therapeutic target for fibrotic diseases, and development of FAP inhibitors for liver fibrosis and idiopathic pulmonary fibrosis (IPF) is also underway. In the present disclosure, FAP is positioned as an extremely useful target molecule in the fields of cancer treatment, fibrotic disease treatment, and diagnostic technology.In particular, the development of FAP-specific targeted treatments and technologies aimed at establishing new diagnostic methods using FAP are expected to play an important role in the medical field in the future.

[0039] As used herein, "cancer stem cells (CSCs)" or "CSCs" refer to a cell population present in tumor tissue, possessing self-renewal and pluripotency, and involved in tumor formation, maintenance, and recurrence. Unlike normal cancer cells, CSCs have the ability to self-renew over long periods of time and differentiate into different cell types, which is thought to contribute to tumor progression and treatment resistance. CSCs, particularly those with a small number of cells, are known to have the ability to form new tumors and can maintain their stem cell properties for long periods within tumor tissue. Furthermore, CSCs exhibit high resistance to chemotherapy and radiotherapy, potentially contributing to cancer recurrence and metastasis after treatment. These properties have been reported to be closely related to their ability to adapt to hypoxic environments and epithelial-mesenchymal transition (EMT). It is believed that progression of EMT, in particular, enhances cancer cell invasiveness and metastatic potential, enhancing the properties of CSCs. CSCs are identified by the expression of specific cell surface markers. For example, the expression of CD44, CD133, ALDH, EpCAM, LGR5, and CD24 / CD44 is known, and the combination of these markers can identify CSCs within tumor tissue. Stem cell-associated transcription factors such as SOX2, OCT4, NANOG, and KLF4 are also involved in the maintenance of CSCs, and cells with high expression levels of these genes are likely to possess CSC characteristics. Furthermore, CSCs often express high levels of drug resistance-associated proteins such as ABCG2 and MDR1 (P-gp), which have the ability to efflux chemotherapeutic agents and thus exhibit resistance to treatment. CSCs have been identified in various cancer types, including breast cancer (CD44 / CD24 / low), brain tumors (CD133), colon cancer (LGR5), and liver cancer (EpCAM / ALDH). As a method for determining whether or not a cell is a CSC, first, the expression of CSC markers such as CD44, CD133, and ALDH can be evaluated using cell surface marker analysis (flow cytometry, FACS).It is also useful to perform a sphere formation assay to confirm whether cells with stem cell properties form spherical clusters under non-adherent conditions. Furthermore, xenograft assays, in which a small number of cells are transplanted into immunodeficient mice to verify their tumorigenic potential, are considered an important criterion for determining CSCs. Drug resistance assays measure the survival rate of CSCs after treatment with anticancer drugs such as cisplatin and doxorubicin to determine whether they exhibit therapeutic resistance. Additionally, gene expression analysis (RT-qPCR, RNA-seq) can be used to analyze the expression levels of stem cell-related genes such as SOX2, OCT4, and NANOG, as well as EMT-related genes such as SNAIL, TWIST1, and ZEB1, allowing for more detailed evaluation of CSC characteristics. As used herein, "cancer stem cells (CSCs)" refer to cells that have these characteristics and are distinguished from cancer stem cell-like cells (CSC-like cells). However, because CSC-like cells may change into CSCs under certain environmental conditions, the term should be defined appropriately depending on the situation.

[0040] As used herein, the term "cancer stem cell-like cells (CSC-like cells, CSCLC)" refers to cells that are involved in the development and progression of tumors and exhibit functions related to treatment resistance, and refer to a cell population in which normal cancer cells have temporarily or partially acquired properties similar to those of cancer stem cells (CSCs) due to specific environmental factors or stimuli. CSC-like cells may exhibit properties similar to those of cancer stem cells, such as self-renewal ability, pluripotency, and treatment resistance, but their expression is environment-dependent and they do not necessarily function as stem cells constitutively. CSC-like cells are known to be induced by external factors such as hypoxic stress, epithelial-mesenchymal transition (EMT), inflammatory responses, chemotherapy, and radiation therapy, and to express markers similar to those of CSCs. Although CSC-like cells express some CSC markers, their expression is not as stable as that of CSCs and may revert to the original cancer cell type upon environmental changes. For example, CSC markers such as CD44, CD133, ALDH, and EpCAM may be transiently expressed, but their expression levels and persistence are often lower than those of CSCs. Furthermore, molecules such as CXCR4, CD49f, c-MET, ZEB2, TGF-β1, N-cadherin (CDH2), and Vimentin (VIM) are likely to be specifically expressed in CSC-like cells but may not be constitutively expressed in CSCs. CSC-like cells are closely related to EMT, and by acquiring mesenchymal characteristics, they acquire invasive and metastatic potential. However, these characteristics are plastic and may change depending on the environment. As used herein, CSC-like cells are defined as cells that, unlike cancer stem cells, exhibit stem cell-like properties only under specific environmental conditions. For example, cancer cells exposed to a hypoxic environment may transform into a CSC-like state via activation of HIF-1α and then revert to normal cancer cells. It is also known that activation of TGF-β signaling causes epithelial cancer cells to transform into CSC-like cells via EMT, thereby acquiring higher invasiveness and drug resistance.Furthermore, it has been observed that a portion of cancer cells exposed to chemotherapy or radiation therapy temporarily transition to a CSC-like state, which may lead to recurrence or metastasis after treatment. While several tests common to CSCs are used to identify CSC-like cells, additional evaluation is required to clarify their differences from CSCs. Cell surface marker analysis (flow cytometry, FACS) assesses the expression of CD44, CD133, ALDH, etc., but it should be noted that the expression of these markers is unstable. A sphere formation assay can be used to confirm whether CSC-like cells have the ability to temporarily form spherical clusters, but they may not exhibit stable sphere formation over the long term. Furthermore, in drug resistance assays, some CSC-like cells exhibit drug resistance, but because they may revert to drug-sensitive cells after treatment, it is necessary to carefully evaluate the difference between these and CSCs that maintain resistance. As used herein, "cancer stem cell-like cells (CSC-like cells)" refer to cells that temporarily acquire stem cell-like properties under specific environmental conditions and are distinguished from cancer stem cells (CSCs). However, because CSC-like cells may transform into CSCs, the term should be appropriately defined depending on the experimental conditions and evaluation method used.

[0041] As used herein, "embryonic stem cells (ES) or cells similar thereto" refers to cells classified as pluripotent stem cells, which have the ability to differentiate into any cell lineage in the body. Pluripotent stem cells include embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells). These cells are important research subjects in development and regenerative medicine, and are expected to serve as a cell source for disease models and cell therapy. ES cells are cells isolated from the inner cell mass (ICM) of a blastocyst stage, and have the ability to differentiate into somatic cells while also continuing to proliferate in an undifferentiated state. ES cells have been established in various species, including humans and mice. Human ES cells, in particular, have been shown to be capable of differentiating into a variety of cells, including neurons, cardiac muscle cells, hepatocytes, and pancreatic islet cells. On the other hand, iPS cells are cells that have been artificially reverted from differentiated somatic cells to pluripotent stem cells using reprogramming factors such as Yamanaka factors (OCT4, SOX2, KLF4, and c-MYC). Like ES cells, iPS cells are pluripotent and can differentiate into neurons, cardiac muscle cells, pancreatic beta cells, and other cells. iPS cells are considered important in regenerative medicine and drug discovery research because they avoid ethical issues and can be produced from a patient's own cells. In addition to these pluripotent stem cells, cloned embryonic stem cells (therapeutic cloning-derived ES cells, NT-ES cells) and stem cells produced from blastocyst-like structures (blastoid-derived stem cells) have also been reported. NT-ES cells are produced using somatic cell nuclear transfer (SCNT) and contain the patient's own genetic information, which has the advantage of a low risk of immune rejection. Furthermore, epiblast stem cells (EpiSCs) and embryonic-like stem cells induced to a pluripotent state (Epiblast-like cells, EpiLCs) are also known as cells with properties similar to pluripotent stem cells. EpiSCs are established from the epiblast and have the same pluripotency as ES cells, but their differentiation potential is more limited than that of ES cells depending on the culture conditions.As used herein, "embryonic stem cells (ES) or cells similar thereto" refers to pluripotent stem cells, including ES cells and iPS cells, and also includes cell populations similar to these, such as NT-ES cells, EpiSCs, and EpiLCs. These cells are expected to be widely applied in regenerative medicine, tissue engineering, disease models, and drug discovery screening, and future research and technological developments are expected to further expand their potential as a new cell source.

[0042] As used herein, the term "cancer stem cell marker (CSC marker)" refers to a molecule used to identify and isolate cancer stem cells (CSCs), and plays an important role in characterizing cell populations involved in cancer development, proliferation, metastasis, and treatment resistance, as well as in targeted therapy. Cancer stem cells have the ability to self-renew and differentiate, and are responsible for tumor formation and recurrence, so the development of diagnostics and treatments targeting these markers is underway. Many cancer stem cell markers have been reported for solid tumors and blood cancers. CSC markers for solid cancers include CD133 (PROM1), LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5), EpCAM (Epithelial Cell Adhesion Molecule), CD13 / APN (Aminopeptidase N), CD24, ALDH (ALDH1A1), CD44v (CD44 variant), and CD90 (Thy-1). On the other hand, for blood cancers, CD34 ＋ / CD38 －, CD123 (IL-3 receptor α), and other markers have been reported as CSC markers. Expression of these markers changes depending on the differentiation state of cancer cells and the tumor microenvironment, and using a single marker or a combination of multiple markers enables more precise identification of cancer stem cells. Furthermore, therapeutic strategies targeting CSC markers, such as monoclonal antibody therapy, CAR-T cell therapy, small molecule inhibitors, and RNA interference technology, are being researched, and the development of treatments aimed at eliminating cancer stem cells is progressing. In this disclosure, by using CSC markers as indicators, we improve the accuracy of cancer stem cell detection and treatment, and provide a novel therapeutic strategy aimed at suppressing cancer progression and preventing recurrence. In addition to the above, cancer stem cell markers (CSC markers) may also include those listed below.

[0043] As used herein, a "cancer stem cell-like cell marker (CSC-like cell marker, CSCLC marker; also referred to as a "CSCLC marker")" is a biomolecule that is involved in the development and progression of tumors and exhibits a function related to treatment resistance, and examples of which include CD133, EGFR / Her2 / neu, CD24, Claudin18.2, Claudin6, FGFR, NRP, c-Met, CD13 / APN, EpCAM, LGR5, CD44v, and CD24, and is expressed when normal cancer cells acquire stem cell-like properties due to specific environmental factors. This includes cell surface markers, transcription factors, metabolism-related factors, signal transduction factors, and the like. CSC-like cells exhibit self-renewal and therapeutic resistance similar to cancer stem cells (CSCs), but their state is plastic and they may lose stem cell-like properties in response to environmental changes. Therefore, although CSCLC markers overlap with CSC markers, there are also CSCLC markers that are not CSC markers. CSC-like cell markers are known to be induced when cancer cells are exposed to external stimuli such as hypoxic environments, epithelial-mesenchymal transition (EMT), inflammatory responses, chemotherapy, and radiation therapy. For example, molecules such as TGF-β1, ZEB2, c-MET, N-cadherin (CDH2), and Vimentin (VIM) are likely to be specifically expressed in CSC-like cells, but may not be constitutively expressed in CSCs. Furthermore, cell surface markers such as CXCR4 and CD49f are known to promote invasion and metastasis, and it has been reported that their expression temporarily increases as EMT progresses. CSC-like cell markers are used as indicators of tumor invasiveness and plasticity, but their expression is unstable, and unlike CSCs, their expression may decrease or disappear when environmental factors are removed. For example, CD44 and CD133 are widely recognized as CSC markers, but although their expression may temporarily increase in CSC-like cells, their expression is not as stable as that of CSCs.On the other hand, ZEB2 and TGF-β1 are specifically expressed in CSC-like cells and enhance the plasticity of cancer cells by inducing EMT, but are not always highly expressed in CSCs. CSC-like cell markers can be evaluated using techniques such as cell surface marker analysis (flow cytometry, FACS), immunostaining, Western blot analysis, and gene expression analysis (RT-qPCR, RNA-seq). In particular, analyzing changes in the expression of CSC-like cell markers in cell populations after chemotherapy or radiation therapy can determine whether cancer cells have acquired stem cell-like properties. For example, cells with increased expression of Vimentin or N-cadherin are thought to have transitioned to a CSC-like state through EMT, but because they do not necessarily possess the self-renewal ability characteristic of CSCs, they are classified as CSCLC Markers but are not considered CSC Markers. CSCLC Markers include those that are different from CSC Markers. CSC Markers are involved in the maintenance of CSCs by being constitutively expressed, but CSC-like Cell Markers can be induced to express in response to environmental changes and can exhibit plastic changes. Some CSC-like Cell Markers are not constitutively expressed in cancer stem cells (CSCs), but their expression is increased in CSC-like cells under certain circumstances. For example, the expression of N-cadherin and Vimentin increases in CSC-like cells as epithelial-mesenchymal transition (EMT) progresses, but they are not necessarily highly expressed in CSCs. Similarly, TGF-β1 and ZEB2 are induced by EMT and stress responses, but are not considered to be constitutive CSC markers in CSCs. Furthermore, c-MET and CXCR4 are known as markers that indicate cancer cell characteristics related to improved metastatic potential, but they do not determine the characteristics of CSCs. Rather, their expression is often temporarily increased in highly invasive CSC-like cells. CD49f is also associated with the transient acquisition of stem cell characteristics in CSC-like cells and is expressed as part of the stress response, but its expression in CSCs is unstable.As such, some CSC-like cell markers are expressed during the process in which cancer cells plastically acquire stem cell-like properties, but because they are not necessarily associated with the stable self-renewal ability or pluripotency of CSCs, they may not be recognized as CSC markers. In this specification, CSC-like cell markers with such properties are clearly distinguished from CSC markers and are appropriately defined taking into consideration their respective roles. In addition to the above, cancer stem cell-like cell markers (CSCLC markers) may also include those listed below.

[0044] Examples of CSC markers include CD44, CD133, ALDH1, EpCAM, LGR5, CD24 / CD44, SOX2, OCT4, NANOG, KLF4, ABCG2, MDR1 (P-gp), etc. These markers are constitutively expressed in cancer stem cells (CSCs) and are involved in maintaining self-renewal ability, pluripotency, tumorigenicity, and therapeutic resistance. Examples of CSCLC markers include CD44, CD133, ALDH1, EpCAM, LGR5, CD24 / CD44, SOX2, OCT4, NANOG, KLF4, ABCG2, MDR1 (P-gp), CXCR4, CD49f, c-MET, TGF-β1, ZEB2, N-cadherin (CDH2), Vimentin (VIM), Slug (SNAI2), and Twist1. Expression of these markers increases when cancer cells acquire stem cell-like properties in response to environmental factors (hypoxia, EMT, chemotherapy, radiotherapy, inflammatory response, etc.), and they serve as indicators for identifying cancer stem cell-like cells (CSC-like cells). While CSC markers are generally also CSCLC markers, there are some CSCLC markers that are not CSC markers, such as CXCR4, CD49f, c-MET, TGF-β1, ZEB2, N-cadherin (CDH2), Vimentin (VIM), Slug (SNAI2), and Twist1. These markers are not necessarily constitutively expressed in cancer stem cells (CSCs), and their expression is often increased during the process in which CSC-like cells temporarily acquire stem cell-like properties in response to specific environmental stimuli. In particular, EMT-related markers such as N-cadherin, Vimentin, Slug, and Twist1, and signal transduction factors such as TGF-β1, ZEB2, and c-MET contribute to the acquisition of cancer cell plasticity and invasive / metastatic potential, but are not essential for the maintenance of CSCs, and therefore may not be classified as CSC markers.

[0045] As used herein, "ES cell-associated markers" refer to molecular markers that are specifically expressed in embryonic stem cells (ES cells) and similar pluripotent stem cells. These markers are involved in maintaining the undifferentiated state and expressing pluripotency, and are used for identifying pluripotent stem cells, including ES cells and induced pluripotent stem cells (iPS cells), as well as for evaluating the differentiation process and quality control. ES cell-associated markers are mainly classified into four categories: transcription factors, cell surface markers, epigenetic markers, and functional markers. Transcription factor markers are factors directly involved in maintaining and controlling pluripotency and are extremely important in determining the undifferentiated state of ES cells. Representative examples include OCT4 (POU5F1, Gene ID: 5460), SOX2 (Gene ID: 6657), NANOG (Gene ID: 79923), KLF4 (Gene ID: 9314), c-MYC (Gene ID: 4609), and LIN28 (Gene ID: 79727). OCT4, SOX2, and NANOG are considered to be the three major pluripotency factors, each playing a central role in regulating the self-renewal and differentiation of ES cells. KLF4 and c-MYC are also known as factors for establishing iPS cells and contribute to the acquisition and maintenance of pluripotency. Cell surface markers are useful for identifying and isolating ES cells and are used to distinguish pluripotent cells from differentiated cells. Representative examples include SSEA-3 (Stage-Specific Embryonic Antigen-3), SSEA-4 (Stage-Specific Embryonic Antigen-4), TRA-1-60, TRA-1-81, CD9 (Gene ID: 928), CD24 (Gene ID: 100133941), and EPCAM (Gene ID: 4072). In particular, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81 are considered important markers that indicate the undifferentiated state of human ES cells and iPS cells. CD9 and CD24 are molecules involved in cell adhesion and intercellular signaling, and are known to affect the proliferation and differentiation of pluripotent stem cells. Epigenetic markers are characteristic of chromatin states and gene expression regulation specific to pluripotent stem cells.Representative examples include histone modification markers (H3K4me3, H3K27me3), DNA methylation patterns (hypomethylated promoter regions), and chromatin remodeling factors (SMARCA4, Gene ID: 6597, CHD1, Gene ID: 1105). Pluripotent stem cells exhibit a characteristic balance of histone modifications (a "bivalent domain" in which both H3K4me3 and H3K27me3 coexist) in the promoter regions of development-related genes, demonstrating that they are ready for differentiation but are regulated to maintain an undifferentiated state. Functional markers refer to molecules and biological behaviors that exhibit the functional characteristics of ES cells and are involved in signaling pathways and metabolic pathways essential for maintaining pluripotency. Representative examples include telomerase (TERT, Gene ID: 7015), LIF (Leukemia Inhibitory Factor, Gene ID: 3976), ALKAL1 (Gene ID: 25992), and TGF-β signaling-related factors (SMAD2, Gene ID: 4087, SMAD3, Gene ID: 4088). Telomerase is necessary to maintain the self-renewal ability of ES cells, and its activity is maintained at a high level in pluripotent stem cells. LIF is an essential factor for maintaining the pluripotency of mouse ES cells and promotes self-renewal via STAT3. On the other hand, it has been shown that in human ES cells, TGF-β signaling is involved in maintaining pluripotency, and transcriptional regulation via SMAD2 / 3 plays an important role in maintaining the undifferentiated state. As described above, "ES cell-associated markers" refer to a group of molecules that serve as important indicators for identifying and evaluating the function of ES cells and similar pluripotent stem cells. These markers are classified based on transcription factors, cell surface antigens, epigenetic regulators, and functional properties, and control the undifferentiated state and pluripotency of ES cells through their respective roles. Analysis of ES cell-associated markers is essential in regenerative medicine, cell therapy, and disease modeling, and it is expected that the discovery of new markers through future research will enable more precise cell control. In addition to the above, the following may also be considered ES cell-associated markers.

[0046] As can be seen from the above explanation, CSC markers, CSCLC markers, and / or ES cell-associated markers may partially overlap. The term "CSCLC marker" is a broad, inclusive term referring to cancer stem cells (CSCs) or markers with partially similar properties. CSCLC markers include a wide variety of markers, including cell surface markers, transcription factors, signal transduction factors, and epigenetic regulators. In particular, SOX2, OCT4, NANOG, KLF4, c-MYC, LIN28, etc., are commonly expressed in ES / iPS cells and are therefore referred to as "undifferentiated, ES cell-associated markers," and are included in the ES cell-associated markers. They are characterized by their involvement in maintaining undifferentiated state and pluripotency. Therefore, in addition to the above-mentioned examples, CSC markers, CSCLC markers, and / or ES cell-associated markers may also include, but are not limited to, the following: [List Z] (Table of CSC markers, CSCLC markers, and ES cell-related markers) (CSC markers) (1) CSC markers for solid tumors 1. CD133 (PROM1) - brain tumor, colon cancer, liver cancer, lung cancer, prostate cancer, pancreatic cancer 2. LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5) - colon cancer, liver cancer, gastric cancer, ovarian cancer 3. EpCAM (Epithelial Cell Adhesion Molecule) - breast cancer, colon cancer, pancreatic cancer, liver cancer 4. CD13 (APN, aminopeptidase N) - liver cancer, pancreatic cancer 5. CD24 - breast cancer, pancreatic cancer, liver cancer, colon cancer 6. ALDH1 (ALDH1A1, aldehyde dehydrogenase 1A1) - breast cancer, colon cancer, lung cancer, prostate cancer 7. CD44v (CD44 variant isoform) - colon cancer, pancreatic cancer, head and neck cancer 8. CD90 (Thy-1) - liver cancer, pancreatic cancer, prostate cancer (2) CSC markers for blood cancer 9. CD34 ＋ / CD38 －-Leukemia (AML, CML) 10. CD123 (IL-3 receptor α) -Leukemia (AML, CML), malignant lymphoma 11. CD47 -Leukemia, breast cancer, pancreatic cancer 12. CD117 (c-Kit) -AML, GIST (gastrointestinal stromal tumor) 13. CD96 -Leukemia (AML) 14. CD25 (IL-2 receptor α) -Adult T-cell leukemia (ATL) (3) CSC marker involved in the control of undifferentiation (also shared with ES / iPS cells, so is also an ES cell-related marker.) 15. OCT4 (POU5F1) - (undifferentiated, ES cell-related marker) Germ cell tumor, prostate cancer, breast cancer 16. 1. SOX2 - (Undifferentiated, ES cell-related marker) Lung cancer, glioma, esophageal cancer 2. NANOG - (Undifferentiated, ES cell-related marker) Breast cancer, prostate cancer, colon cancer 3. KLF4 - (Undifferentiated, ES cell-related marker) Gastric cancer, colon cancer, pancreatic cancer 4. LIN28A / B - (Undifferentiated, ES cell-related marker) Breast cancer, liver cancer, colon cancer 5. ZEB1 - (Undifferentiated, ES cell-related marker) Lung cancer, pancreatic cancer, colon cancer 6. (4) Other CSC markers 7. Bmi-1 - Breast cancer, pancreatic cancer, prostate cancer 8. Notch1 - Breast cancer, pancreatic cancer, colon cancer 9. Jagged1 - Breast cancer, pancreatic cancer, liver cancer 10. 2. DLL4 (Delta-like ligand 4) - breast cancer, colon cancer, liver cancer 25. AXL - lung cancer, pancreatic cancer, breast cancer 26. TGF-β1 - lung cancer, breast cancer, prostate cancer 27. EGFR (Epidermal Growth Factor Receptor) - breast cancer, lung cancer, colon cancer 28. HER2 (ERBB2) - breast cancer, gastric cancer, pancreatic cancer 29. MET (HGF receptor) - liver cancer, kidney cancer, pancreatic cancer 30. Twist1 - breast cancer, pancreatic cancer, prostate cancer 31. Slug (SNAI2) - breast cancer, pancreatic cancer, colon cancer 32. FOXM1 - liver cancer, pancreatic cancer, breast cancer 33. BMI-1 - Leukemia, pancreatic cancer, prostate cancer 34. Nestin - Glioma, pancreatic cancer, prostate cancer 35. CD166 (ALCAM, Activated Leukocyte Cell Adhesion Molecule) - Colon cancer, breast cancer, pancreatic cancer 36. CXCR4 - Breast cancer, prostate cancer, pancreatic cancer37. PLOD2 - Liver cancer, lung cancer, pancreatic cancer 38. Msi1 (Musashi-1) - Glioma, pancreatic cancer, colon cancer 39. CD271 (NGFR, Nerve Growth Factor Receptor) - Breast cancer, prostate cancer, glioma 40. ALCAM - Liver cancer, colon cancer, pancreatic cancer 41. ITGA6 (Integrin α6) - Breast cancer, pancreatic cancer, glioma 42. ABCG2 - Breast cancer, lung cancer, colon cancer 43. ID1 (Inhibitor of DNA binding 1) - Lung cancer, pancreatic cancer, colon cancer 44. 43. ID3 (Inhibitor of DNA binding 3) - Breast cancer, liver cancer, pancreatic cancer 44. GPR49 (LGR5, Leucine-rich repeat-containing G-protein coupled receptor 5) - Colon cancer, liver cancer 45. TCF4 - (Undifferentiated, ES cell-associated marker) Colon cancer, liver cancer 46. TCF4 - (Undifferentiated, ES cell-associated marker) Colon cancer, liver cancer 47. TCF7L2 - (Undifferentiated, ES cell-associated marker) Colon cancer, liver cancer 48. HMGA2 - (Undifferentiated, ES cell-associated marker) Pancreatic cancer, colon cancer 49. SALL4 - (Undifferentiated, ES cell-associated marker) Liver cancer, leukemia, germ cell tumor 50. PRDM14 - (Undifferentiated, ES cell-related marker) Breast cancer, germ cell tumors (Note) In particular, OCT4, SOX2, NANOG, LIN28, KLF4, SALL4, PRDM14, etc. are commonly expressed in ES / iPS cells and are important factors that control undifferentiated state. (CSCLC Markers) (1) Cell Surface Markers 1. CD44 - Breast cancer, colon cancer, pancreatic cancer, prostate cancer, gastric cancer, head and neck cancer, etc. 2. CD133 (Prominin-1) - Brain tumor (glioblastoma), lung cancer, colon cancer, pancreatic cancer, hepatocellular carcinoma 3. CD24 - Breast cancer, colon cancer, pancreatic cancer, hepatocellular carcinoma 4. CD90 (Thy-1) - Hepatocellular carcinoma, leukemia, esophageal cancer 5. 5. CD105 (Edoglin) - breast cancer, colon cancer, pancreatic cancer, hepatocellular carcinoma 6. CD117 (c-KIT) - leukemia (CML, AML), gastric cancer, lung cancer, testicular tumor 7. CD166 (ALCAM) - colon cancer, breast cancer, prostate cancer 8. EpCAM (Epithelial Cell Adhesion Molecule) - breast cancer, pancreatic cancer, colon cancer, hepatocellular carcinoma9. CD200 - Leukemia, glioma 10. LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5) - Colon cancer, stomach cancer, ovarian cancer (2) Metabolic enzymes & drug resistance 11. ALDH1 (Aldehyde dehydrogenase 1) - Breast cancer, colon cancer, lung cancer, pancreatic cancer, ovarian cancer 12. ABCG2 (ATP-binding cassette sub-family G member 2) - Breast cancer, lung cancer, pancreatic cancer, hepatocellular carcinoma 13. (3) Transcription Factors 15. SOX2 (SRY-box transcription factor 2) - Lung cancer, breast cancer, esophageal cancer, glioblastoma (undifferentiated, ES cell-related marker) 16. OCT4 (Octamer-binding transcription factor 4) - Testicular cancer, pancreatic cancer, breast cancer (undifferentiated, ES cell-related marker) 17. 18. NANOG - breast cancer, hepatocellular carcinoma, pancreatic cancer, testicular cancer (undifferentiated, ES cell-related marker) 19. MYC (c-Myc, Proto-oncogene) - breast cancer, prostate cancer, colon cancer (undifferentiated, ES cell-related marker) 20. BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) - leukemia, pancreatic cancer, prostate cancer 21. ZEB1 (Zinc finger E-box-binding homeobox 1) - breast cancer, pancreatic cancer, lung cancer 22. SNAIL (SNAI1) - breast cancer, pancreatic cancer, colon cancer 23. TWIST1 - breast cancer, prostate cancer, head and neck cancer (4) Signaling Pathway Regulators 24. Notch1 - breast cancer, leukemia, pancreatic cancer25. Jagged1 (Notch ligand) - Breast cancer, colon cancer, hepatocellular carcinoma 26. DLL3 (Delta-like 3, Notch ligand) - Small cell lung cancer, neuroendocrine tumor 27. Hedgehog (SHH, Sonic Hedgehog) - Pancreatic cancer, lung cancer, prostate cancer 28. GLI1 (Zinc finger protein GLI1, Hedgehog pathway effector) - Pancreatic cancer, leukemia, glioma 29. WNT1 (Wingless-type MMTV integration site family, member 1) - colon cancer, breast cancer, ovarian cancer 30. β-catenin (CTNNB1, Wnt signaling pathway effector) - colon cancer, breast cancer, pancreatic cancer 31. AXIN2 (Negative regulator of Wnt signaling) - colon cancer, gastric cancer (5) Epigenetic Regulators 32. 3. EZH2 (Enhancer of zeste homolog 2, Polycomb Repressive Complex 2) - breast cancer, prostate cancer, pancreatic cancer 33. DNMT1 (DNA methyltransferase 1) - leukemia, breast cancer, colon cancer 34. TET1 (Ten-eleven translocation methylcytosine dioxygenase 1) - leukemia, glioblastoma (6) RNA-binding proteins and others 35. LIN28A / B - breast cancer, hepatocellular carcinoma, pancreatic cancer (undifferentiated, ES cell-related marker) 36. 37. Msi1 (Musashi RNA-binding protein 1) - glioblastoma, colon cancer, pancreatic cancer 37. ELAVL1 (HuR, ELAV-like RNA-binding protein 1) - breast cancer, lung cancer 38. TARBP2 (TAR RNA-binding protein 2, microRNA processing factor) - colon cancer, breast cancer (7) Cell Cycle Regulators 39. Cyclin D1 (CCND1) - breast cancer, colon cancer, prostate cancer40. p21 (CDKN1A, Cyclin-dependent kinase inhibitor 1A) - Leukemia, breast cancer, pancreatic cancer 41. p27 (CDKN1B, Cyclin-dependent kinase inhibitor 1B) - Prostate cancer, stomach cancer

[0047] In cancer treatment and prevention, ES cell-associated markers play an important role in the identification and characterization of cancer stem cells (CSCs) and the development of targeted therapies. Numerous studies have shown that pluripotent stem cell markers, such as OCT4, SOX2, NANOG, and KLF4, are highly expressed in some cancer stem cells. These markers are being used to identify cancer stem cells and develop new diagnostic methods. In particular, the presence of cancer stem cells has been shown to cause treatment resistance and metastasis, and therapeutic strategies targeting ES cell-associated markers are being explored. For example, cancer cells with high expression of OCT4 and SOX2 may exhibit resistance to conventional anticancer drugs and radiation therapy. Suppressing these markers may reduce the self-renewal ability of cancer stem cells and potentially improve therapeutic efficacy. In addition, antibody drugs and CAR-T cell therapies targeting cell surface markers such as SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81 are being developed, and are expected to be effective treatments for selectively eliminating specific cancer cell populations. Furthermore, abnormalities in epigenetic markers such as histone modifications and DNA methylation are closely related to the development and progression of cancer, and therapies targeting ES cell-related epigenetic regulators are also being investigated. For example, abnormal patterns of H3K4me3 and H3K27me3 in cancer cells have been suggested to be involved in the maintenance of cancer stem cells and resistance to treatment, and development of small molecule inhibitors targeting these modifications is underway. Furthermore, TGF-β signaling and LIF-STAT3 signaling, which are involved in the regulation of ES cell differentiation, are also activated in some cancer cells, and inhibiting these signaling pathways can suppress cancer cell proliferation and metastasis. From the perspective of cancer prevention, it has been reported that the abnormal expression of ES cell-related markers is associated with the risk of developing cancer, and it is hoped that using these markers as biomarkers will improve the accuracy of early diagnosis and risk assessment. As described above, ES cell-related markers play an important role in the treatment and prevention of cancer, including the characterization of cancer stem cells, the identification of therapeutic targets, and the development of new diagnostic techniques, and it is hoped that future research progress will lead to the establishment of new treatments.

[0048] Although not all ES cell-associated markers herein are CSC markers or CSCLC markers, at least those that suggest a relationship with cancer are within the scope of the present disclosure. Many ES cell-associated markers function as indicators of the undifferentiated state of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), and some of these markers have been suggested to be involved in the maintenance and tumor progression of cancer stem cells (CSCs) and cancer stem-like cells (CSCLCs). For example, cell surface markers containing carbohydrate antigens such as LIN28, OCT4 (POU5F1), SOX2, NANO, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81 are used as specific markers for ES cells, but their expression has been observed in some cancer cells and cancer stem cells, potentially affecting cancer progression and metastasis. Furthermore, the epigenetic markers H3K4me3 and H3K27me3 have been suggested to be involved in the regulation of stem cell differentiation and gene expression in cancer cells. Therefore, among ES cell-related markers, those that are suggested to be involved in the maintenance of cancer stem cells, tumor formation, metastasis, treatment resistance, etc. are considered to be within the scope of the present disclosure.

[0049] As used herein, "CD133" refers to a transmembrane glycoprotein, also known as prominin-1, which is a specific cell surface marker localized to the cell membrane. CD133 is known to be highly expressed in cancer stem cells (CSCs) and undifferentiated progenitor cells, and is recognized as an important molecule particularly associated with tumorigenicity and therapeutic resistance. In humans, CD133 corresponds to gene ID: 8842 and is encoded by the PROM1 gene located on chromosome 4, 4p15.32. This protein has a molecular weight of approximately 120 kDa and a characteristic structure with five transmembrane domains. It has been reported that the N- and C-termini are exposed extracellularly and specifically localize to protrusions (microvilli) of the cell membrane. CD133 is widely used as a cancer stem cell marker in various cancer types, and its expression has been confirmed in brain tumors (glioblastoma), colorectal cancer, lung cancer, pancreatic cancer, liver cancer, and breast cancer. CD133-positive cancer cells have the ability to self-replicate and are involved in tumor maintenance, metastasis, and the acquisition of drug resistance, making them a promising indicator of cancer malignancy. CD133-positive cells are also known to exhibit resistance to chemotherapy and radiation therapy and cause cancer recurrence. The physiological roles of CD133 include stem cell maintenance, signal transduction, and regulation of cell differentiation, but the detailed molecular mechanisms have not yet been fully elucidated. Meanwhile, CD133 expression has been suggested not only for the identification of cancer stem cells but also as a potential therapeutic target. In recent years, immunotherapy using CD133-specific antibodies and CD133-targeted CAR-T cell therapy have been developed, and these promising approaches to cancer treatment are expected. Furthermore, diagnostic techniques targeting CD133 have also been developed, and analysis of CD133 expression levels in circulating tumor cells (CTCs) and tumor tissues is being utilized to evaluate the progression of cancer and the effectiveness of treatment. In particular, attempts are being made to visualize the distribution and dynamics of cancer stem cells using imaging techniques targeting CD133. In the present disclosure, CD133 is positioned as a molecule that plays an important role in cancer treatment, control of cancer stem cells, and diagnostic techniques.In particular, the development of therapeutic methods targeting CD133 and the advancement of diagnostic techniques are extremely important in the pursuit of a complete cure for cancer, and are expected to be part of new treatment strategies in the medical field in the future.

[0050] As used herein, "LGR5" is an abbreviation for leucine-rich repeat-containing G-protein coupled receptor 5, and refers to a type of G protein-coupled receptor (GPCR) containing leucine-rich repeats. LGR5 functions as a stem cell marker and a cancer stem cell (CSC) marker, and is known to be involved in the maintenance of stem cells, particularly in epithelial tissues of the digestive system. In humans, LGR5 corresponds to gene number GeneID: 8549 and is encoded by the LGR5 gene located on chromosome 12, 12q21.1. This protein has a molecular weight of approximately 100 kDa and is a G protein-coupled receptor with seven transmembrane domains. However, unlike typical GPCRs, it does not transmit signal via G proteins, but functions as an amplifier of the Wnt / β-catenin signal. LGR5 does not directly bind to Wnt ligands, but rather binds to the R-spondin family (RSPO1-4) and promotes the activation of Wnt signaling. LGR5 is expressed in epithelial stem cells, particularly in the intestine, stomach, hair follicles, and ovaries, and is involved in the self-renewal and differentiation of stem cells in these tissues. In the intestinal epithelium, LGR5 is highly expressed in stem cells located near Paneth cells and is known to play an important role in the homeostatic turnover of the small intestine and large intestine. Meanwhile, LGR5 has also been widely studied as a cancer stem cell marker, and it has been reported that LGR5-positive cells in colon cancer, gastric cancer, pancreatic cancer, hepatocellular carcinoma, ovarian cancer, and other cancers possess tumorigenic and metastatic potential. LGR5-positive cancer cells have been shown to exhibit resistance to chemotherapy and radiotherapy and increase the risk of recurrence after treatment. Therefore, LGR5 has become an important target in the development of therapies targeting cancer stem cells. In recent years, research into cancer treatments targeting LGR5 has progressed, and for example, LGR5-specific CAR-T cell therapy and LGR5 antibody-drug conjugates (ADCs) are being developed. In addition, research is also underway into small molecule compounds that specifically eliminate LGR5-expressing cells, which are expected to be a new treatment strategy for suppressing cancer progression and recurrence.Furthermore, LGR5 is also a promising diagnostic marker for cancer, and measuring the expression level of LGR5 in circulating tumor cells (CTCs) or tumor tissues makes it possible to evaluate tumor malignancy and therapeutic efficacy. In particular, imaging techniques targeting LGR5 are advancing the visualization of cancer stem cells, which is expected to improve the accuracy of cancer diagnosis. In this disclosure, LGR5 is positioned as an important molecule in the fields of stem cell maintenance, cancer stem cell control, and diagnostic technology. In particular, the development of new cancer treatments targeting LGR5 and innovations in diagnostic technology may contribute to preventing cancer recurrence and improving therapeutic efficacy, and are expected to play an important role in the future medical field.

[0051] As used herein, "EpCAM (Epithelial Cell Adhesion Molecule)" refers to a transmembrane glycoprotein responsible for adhesion between epithelial cells, with diverse functions including cell adhesion, signal transduction, cell proliferation, differentiation, and stem cell maintenance. EpCAM is known to be highly expressed, particularly in epithelial cancers, and has been widely studied as a marker for cancer stem cells (CSCs) and a target for cancer diagnosis and treatment. In humans, EpCAM corresponds to gene ID: 4072 and is encoded by the EPCAM gene located on chromosome 2, 2p21. This protein has a molecular weight of approximately 40 kDa and is a single-pass transmembrane glycoprotein composed of three major regions: an extracellular domain (N-terminus), a transmembrane domain, and an intracellular domain (C-terminus). EpCAM functions as an adhesion factor for epithelial cells, promoting cell-cell adhesion. However, unlike conventional cadherins and integrins, it also activates Wnt / β-catenin signaling and plays a role in maintaining cell proliferation and stemness. Therefore, while it is an important molecule for maintaining epithelial cell homeostasis, its abnormal expression may promote cancer progression and metastasis. EpCAM expression is observed in many epithelial cancers, including breast cancer, colon cancer, gastric cancer, pancreatic cancer, hepatocellular carcinoma, lung cancer, and ovarian cancer, and is particularly known as a marker of cancer stem cells. EpCAM-positive cancer cells have been reported to have self-renewal capabilities and are involved in tumor formation, recurrence, and drug resistance. Its expression level can be used as an indicator of cancer malignancy and prognosis. EpCAM is also important as a marker for circulating tumor cells (CTCs) and is used to detect cancer cells released into the blood. The detection of CTCs is extremely important in assessing the progression of cancer and the risk of metastasis, and analytical techniques using immunomagnetic separation and microfluidic devices targeting EpCAM have been established. In recent years, EpCAM has also attracted attention as a target molecule for cancer therapy, and the development of EpCAM-specific antibody drugs (e.g., catumaxomab, adecatumumab) and EpCAM-targeted CAR-T cell therapy is progressing.Furthermore, cancer imaging technology using radiolabeled EpCAM antibodies has also been developed, which is expected to contribute to improving the accuracy of cancer diagnosis. In this disclosure, EpCAM is positioned as a molecule that plays an extremely important role in the fields of cancer diagnosis, cancer stem cell control, and cancer treatment technology. In particular, the development of new cancer treatments targeting EpCAM and the advancement of diagnostic technology may contribute to the early detection of cancer and the prevention of recurrence, and are expected to make a significant contribution to the medical field in the future.

[0052] As used herein, "CD44v" or "CD44" refers to a transmembrane glycoprotein involved in cell adhesion, cell migration, and signal transduction, and a molecule that regulates various physiological and pathological processes through interactions with the extracellular matrix (ECM). CD44, with hyaluronic acid (HA) as its primary ligand, is known to be involved in cell adhesion and migration, cancer progression, inflammatory responses, tissue regeneration, and other processes. In humans, CD44 corresponds to gene ID: 960 and is encoded by the CD44 gene located on chromosome 11, 11p13. This protein has a molecular weight of approximately 85-200 kDa and is composed of three main regions: an extracellular domain, a transmembrane domain, and an intracellular domain. In particular, various isoforms are generated by the incorporation of different exons into the extracellular domain of CD44 through alternative splicing. CD44 exists in two forms: the standard form (CD44s) and the variant form (CD44v), which contains specific variable regions due to alternative splicing. CD44v has a different function from CD44s and has been reported to be upregulated in certain cancer cells and stem cells. In particular, isoforms such as CD44v6 and CD44v8-10 are believed to be involved in epithelial-mesenchymal transition (EMT), cancer invasion / metastasis, and drug resistance, and have been widely studied as cancer stem cell (CSC) markers. The physiological roles of CD44 and CD44v include the following: First, CD44 binds to ECM components such as hyaluronic acid, collagen, and fibronectin, regulating cell migration and adhesion, thereby contributing to cell migration and maintaining tissue homeostasis. Second, CD44 interacts with Rho family GTPases, Ras / MAPK, and PI3K / Akt pathways, regulating cell proliferation and survival, thereby contributing to the regulation of signal transduction. Third, CD44 is also involved in immune cell homing and the regulation of inflammatory cytokine expression, contributing to the regulation of inflammatory responses. Furthermore, CD44 and CD44v have attracted particular attention as cancer stem cell markers, and CD44v expression has been confirmed in colon cancer, breast cancer, pancreatic cancer, head and neck cancer, prostate cancer, and other cancers.CD44v-positive cancer cells have been reported to exhibit resistance to chemotherapy and radiotherapy and promote tumor recurrence and metastasis. Therefore, CD44v has become an important target in the development of therapies targeting cancer stem cells. Several strategies are being investigated as approaches to cancer treatment targeting CD44v. For example, CD44v-specific antibody drugs (anti-CD44v6 antibody, anti-CD44v8-10 antibody) and CD44-targeting CAR-T cell therapy have been developed, and these are expected to be therapeutic approaches that specifically eliminate CD44-positive cancer cells. Furthermore, development of small molecules that inhibit CD44-hyaluronan binding is also underway and is being considered as part of a new therapeutic strategy to suppress cancer progression and recurrence. Furthermore, CD44 is also used as a marker for circulating tumor cells (CTCs), potentially applicable to cancer diagnosis and therapeutic monitoring. Analysis of CD44v expression in blood and tissue samples is thought to be useful for assessing the malignancy and prognosis of cancer. In particular, the development of imaging techniques targeting CD44v is progressing, and it is expected that this will lead to improved techniques for observing the dynamics of cancer stem cells in real time.

[0053] As used herein, "CD13 / APN" refers to a transmembrane zinc-dependent metalloprotease, also known as aminopeptidase N (APN), which is a glycoprotein present on the cell surface. CD13 / APN has the enzymatic activity of sequentially cleaving the N-terminal amino acids of peptides and is known to be involved in proteolysis, regulation of peptide hormones, and cell signaling. This molecule has also been reported to be involved in a variety of physiological and pathological processes, such as angiogenesis, immune response, and cancer progression and metastasis. In humans, CD13 corresponds to gene number GeneID: 290 and is encoded by the ANPEP gene located on chromosome 15, 15q26.1. This protein has a molecular weight of approximately 150-180 kDa and a transmembrane structure. The N-terminus is exposed to the extracellular space, and the catalytic domain responsible for peptidase activity is present in the extracellular region. CD13 / APN is a zinc-dependent protein. ２＋CD13 / APN possesses a cytotoxic metalloprotease activity, specifically hydrolyzing a single amino acid at the N-terminus. This allows it to regulate the degradation of bioactive peptides in blood and tissues, contributing to neurotransmission, blood pressure regulation, and immune response control. CD13 / APN regulates cell migration and tissue repair, particularly in endothelial cells, promoting angiogenesis and playing an important role in wound healing and angiogenesis in the tumor microenvironment. CD13 is also expressed on immune cells such as monocytes, macrophages, and dendritic cells, suggesting its role in antigen presentation and inflammatory responses. Furthermore, it has been reported to function as a receptor for some viruses (e.g., coronaviruses) and participate in the infection process. CD13 / APN also plays an important role in the tumor microenvironment, where it is highly expressed on tumor cells and cancer-associated fibroblasts (CAFs) and is known to promote tumor invasion and metastasis. High expression of CD13 has been observed in particular in renal cell carcinoma, pancreatic cancer, hepatocellular carcinoma, prostate cancer, lung cancer, and other cancers, suggesting a relationship with tumor progression and treatment resistance. Furthermore, because CD13-positive cancer stem cells (CSCs) exhibit resistance to chemotherapy and radiotherapy and may promote cancer recurrence and metastasis, the development of cancer therapies targeting CD13 is underway. CD13-targeting therapeutic approaches include the development of CD13 inhibitors, CD13-specific antibodies, CD13-targeted CAR-T cell therapy, and CD13-targeted diagnostic technologies. For example, bestatin (Ubenimex) specifically inhibits CD13 and is used clinically as a drug that suppresses cancer progression and induces immune activation. Furthermore, immunotherapy using CD13-specific monoclonal antibodies and CAR-T cell therapy for eliminating CD13-positive cancer stem cells are being studied, with the potential to suppress cancer recurrence. Furthermore, imaging technologies for CD13-expressing tumors (PET, SPECT) are being developed, which may contribute to improving the accuracy of cancer diagnosis. In this disclosure, CD13 / APN is positioned as an important target molecule in the development of cancer treatment, anti-angiogenic therapy, treatment of inflammatory and fibrotic diseases, and diagnostic technology.In particular, the development of CD13 inhibitors and CD13-targeted immunotherapy may contribute to suppressing cancer progression and preventing recurrence, and is expected to make a significant contribution to the medical field in the future.

[0054] As used herein, "CD24" refers to a transmembrane glycoprotein expressed on the cell surface, a molecule involved in immune response regulation, cell adhesion, and signal transduction. CD24 is particularly highly expressed in immune cells, cancer cells, and stem cells, and is known to play an important role in cancer progression, treatment resistance, and immune evasion mechanisms. In humans, CD24 corresponds to gene ID: 100133941 and is encoded by the CD24 gene located on chromosome 6, 6q21. This protein has a molecular weight of approximately 30-60 kDa and binds to the cell membrane as a glycosylphosphatidylinositol (GPI)-anchored glycoprotein. The extracellular domain of CD24 is highly glycosylated, and this glycosylation has an important impact on its function. One of the primary physiological roles of CD24 is immune response regulation. CD24 induces immunosuppressive signals by binding to Siglec-10, thereby preventing autoimmune responses. CD24 also plays a role in regulating the activity of dendritic cells (DCs) and macrophages and modulating inflammatory responses. Furthermore, CD24 is highly expressed in cancer cells and is known to contribute to tumor growth, metastasis, and drug resistance. Its expression has been reported to be particularly elevated in breast cancer, colon cancer, lung cancer, pancreatic cancer, ovarian cancer, and hepatocellular carcinoma. CD24 also functions as a cancer stem cell (CSC) marker and is involved in cancer cell self-renewal and post-treatment recurrence. CD24 also plays an important role in cell adhesion and signal transduction. It is known to interact with adhesion molecules such as P-selectin and promote cancer cell metastasis. It also activates Src family kinases and enhances cell survival signals. In addition, CD24 is involved in inflammation and autoimmune diseases, and polymorphisms in the CD24 gene have been suggested to be associated with disease risk in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Because CD24 is involved in immune evasion and cancer progression, development of CD24-targeted therapies is underway. A representative therapeutic approach targeting CD24 is CD24-specific antibody therapy.Specific removal of CD24-positive cancer cells using monoclonal antibodies (mAbs) is currently being studied, and development of targeted therapy using anti-CD24 antibody-drug conjugates (ADCs) is also underway. Furthermore, because CD24 is known to suppress phagocytosis by macrophages by emitting a "don't eat me" signal, attempts are being made to enhance anti-tumor immunity by inhibiting this pathway. To this end, immune checkpoint blockade therapy using anti-CD24 antibodies (CD24-Fc fusion proteins) is being investigated. Another approach to cancer treatment targeting CD24 is CD24-targeted CAR-T cell therapy. This therapy specifically recognizes and eliminates CD24-positive cancer stem cells (CSCs), thereby suppressing cancer progression and recurrence, and is particularly promising as a novel treatment for refractory cancers.

[0055] As used herein, "ALDH (ALDH1A1)" refers to a type of aldehyde dehydrogenase, an enzyme that oxidizes aldehydes intracellularly and converts them to the corresponding carboxylic acids. ALDH1A1 is particularly involved in the biosynthesis of retinoic acid (RA) and cellular oxidative stress response, and is known to play an important role in normal and cancer tissues. In particular, this enzyme has been widely studied as a marker for cancer stem cells (CSCs) and has attracted attention as a molecule involved in tumor growth, treatment resistance, and metastasis. In humans, ALDH1A1 corresponds to gene ID: 216 and is encoded by the ALDH1A1 gene located on chromosome 9, 9q21.13. This protein has a molecular weight of approximately 54 kDa and is localized in the cytoplasm and some organelles (mitochondria and endoplasmic reticulum). ALDH1A1 is a NAD ＋ or NADP ＋ALDH1A1 utilizes α-reductase (α-reductase) as a coenzyme to oxidize compounds containing aldehyde groups, such as acetaldehyde and retinal, thereby contributing to their metabolism and detoxification. The physiological role of ALDH1A1 is first to regulate retinoic acid (RA) synthesis. By converting retinal to RA, this enzyme is involved in regulating cell differentiation and developmental processes, and also contributes to neurogenesis and immune response regulation. Second, this enzyme functions to protect cells from oxidative stress by degrading harmful aldehydes generated by reactive oxygen species (ROS). Specifically, it plays a role in suppressing cell damage by promoting the metabolism of reactive aldehydes such as acetaldehyde, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE). Furthermore, it is known to be involved in the acquisition of drug resistance and improve cancer cell survival by mitigating the oxidative stress response induced by chemotherapeutic agents (e.g., cisplatin and paclitaxel). Cancer cells with high ALDH1A1 activity may suppress DNA damage responses and exhibit resistance to radiation therapy. ALDH1A1 is widely recognized as a cancer stem cell (CSC) marker, and high-expression ALDH1A1 cells have been reported, particularly in breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, and ovarian cancer. ALDH1A1-positive cancer cells have high self-replication capacity, tumorigenic potential, and often exhibit resistance to chemotherapy and radiation therapy. Therefore, the development of cancer therapies targeting ALDH1A1 is underway. As a therapeutic strategy targeting ALDH1A1, the development of ALDH1A1 inhibitors is underway. For example, diethylaminobenzaldehyde (DEAB) and N,N-dimethylaminobenzaldehyde (DMAB) are known as ALDH1A1 inhibitors, and the development of small molecule compounds that inhibit cancer stem cell function by suppressing ALDH1A1 activity is underway. Furthermore, ALDH1A1-specific CAR-T cell therapy is being developed as an ALDH1A1-targeted immunotherapy, and a therapeutic strategy to specifically eliminate ALDH1A1-positive cancer stem cells is being investigated. Furthermore, ALDH1A1 vaccine therapy is also being developed, and attempts are being made to activate the immune system of cancer patients and eliminate ALDH1A1-positive cancer cells.In addition, the development of diagnostic technologies targeting ALDH1A1 is also progressing. Imaging technologies (PET, SPECT) aimed at visualizing ALDH1A1-expressing tumors and analysis of ALDH1A1 expression in circulating tumor cells (CTCs) are progressing, and these technologies may be used to evaluate the progression of cancer and the effectiveness of treatment. In the present disclosure, ALDH1A1 is positioned as an extremely important target molecule in the control of cancer stem cells, cancer treatment, and the development of diagnostic technologies. In particular, the development of new cancer treatments targeting ALDH1A1 and the improvement of diagnostic technologies may contribute to the inhibition of cancer progression and the prevention of recurrence, and are expected to make a significant contribution to the medical field in the future.

[0056] As used herein, "CD34 ＋ / CD38 － " refers to a combination of cell surface markers that characterize hematopoietic stem cells (HSCs) and cancer stem cells (CSCs). ＋ / CD38 － These cells have the ability to self-renew and constitute a population of undifferentiated cells with pluripotency, and are considered important as a subset exhibiting stem cell properties, particularly in hematopoietic stem cells and in some solid cancers. CD34 corresponds to gene number GeneID: 947 in humans and is encoded by the CD34 gene located on chromosome 1 1q32.2. This protein is a transmembrane glycoprotein that undergoes glycosylation and is expressed in undifferentiated cells such as hematopoietic stem cells, endothelial progenitor cells, and mesenchymal stem cells. CD34 is responsible for regulating the survival and differentiation of hematopoietic stem cells through regulation of cell adhesion, stem cell maintenance, and interaction with the bone marrow niche. On the other hand, CD38 corresponds to gene number GeneID: 952 in humans and is encoded by the CD38 gene located on chromosome 4 4p15. This protein is expressed in NAD ＋ It has hydrolase activity and is involved in intracellular signal transduction and energy metabolism, and is expressed in mature lymphocytes, plasma cells, and some hematopoietic cells. CD38 is highly expressed in differentiated cells, and is characterized by low or almost absent expression in undifferentiated stem cells. ＋ / CD38－ These cells mainly refer to an undifferentiated subset of hematopoietic stem cells (HSCs), and stem cells with long-term self-renewal potential (LT-HSCs) present in bone marrow exhibit this phenotype. These cells have the ability to generate progenitor cells of blood cells and play an important role in bone marrow transplantation and regenerative medicine. In addition, CD34 ＋ / CD38 － CD34 cells are sometimes specifically expressed in leukemia and solid cancers, and are also used as an indicator of cancer stem cells (CSCs). In particular, CD34 is expressed in leukemia stem cells (LSCs). ＋ / CD38 － These cells are thought to be involved in the maintenance and recurrence of tumors. For example, in acute myeloid leukemia (AML), this subset of cells is thought to be resistant to chemotherapy and to be a major cause of leukemia recurrence. ＋ / CD38 － Therapies targeting CD34 cells are currently being developed. ＋ / CD38 － Therapeutic strategies targeting CD34 include the following approaches: ＋ / CD38 － There is specific antibody therapy. Treatments using monoclonal antibodies (mAbs) targeting CD34 or CD38 have been developed, and as an example, the anti-CD38 antibody daratumumab is clinically used for multiple myeloma. Daratumumab has the effect of eliminating CD38-positive cells, but because CD38 expression is low in leukemia stem cells, new target molecules are being explored. Secondly, CD34 ＋ / CD38 － CAR-T cell therapy is being developed that targets CD34-positive cancer stem cells by genetically modifying the patient's own T cells. ＋ / CD38 － This technology selectively eliminates cancer stem cells by returning them to the body as CAR-T cells that specifically recognize CD34. Research is currently underway aimed at curing leukemia in particular. ＋ / CD38 －Cellular diagnostic and monitoring techniques include CD34 using flow cytometry analysis. ＋ / CD38 － Detection of CD34 cells is used for diagnosing leukemia and evaluating the effectiveness of treatment, and furthermore, technology is being developed to evaluate the progression of cancer in real time by analyzing circulating tumor cells (CTCs). ＋ / CD38 － CD34 is considered to be a very important target molecule in the maintenance of stem cells, the control of leukemia stem cells, and the development of cancer treatment and diagnostic technology. ＋ / CD38 － Treatments that target positive cells and improvements in diagnostic techniques may contribute to suppressing cancer progression and preventing recurrence, and are expected to make a major contribution to the medical field in the future.

[0057] As used herein, "CD123 (IL-3 receptor α)" refers to the α subunit of IL-3R, a receptor for interleukin 3 (IL-3), and is a transmembrane glycoprotein expressed on the cell surface of hematopoietic cells, immune cells, leukemia stem cells (LSCs), and other cells. CD123 is involved in cell proliferation, differentiation, and survival, and has been reported to be abnormally expressed in hematopoietic tumors, particularly acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). In humans, CD123 corresponds to gene number GeneID: 3563 and is encoded by the IL3RA gene located on chromosome X, Xp22.3-p22.2. This protein has a molecular weight of approximately 60-70 kDa and is a transmembrane type I glycoprotein expressed on the cell membrane. IL-3R is composed of CD123 (IL-3Rα) and a common β subunit (CD131, IL-3Rβc). CD123 alone functions as a low-affinity receptor for IL-3, but upon binding to CD131, it forms a high-affinity IL-3 receptor complex, which transduces signals. CD123 plays an important role in regulating the proliferation and differentiation of hematopoietic cells, promoting the proliferation and differentiation of myeloid progenitor cells through IL-3 signaling, thereby controlling the production of erythrocytes, neutrophils, monocytes, mast cells, and other cells. It is also known to be involved in the maintenance of hematopoietic stem cells and the maturation of hematopoietic progenitor cells. Furthermore, CD123 contributes to the regulation of immune responses, promoting the differentiation of macrophages and dendritic cells (DCs) through IL-3 signaling and thereby activating innate immunity. In particular, it regulates the function of basophils and mast cells, and is also involved in the control of allergic and inflammatory responses. CD123 also plays an important role in the maintenance and proliferation of tumor cells. Abnormal expression of CD123 has been observed in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS), and it has been shown that it is particularly highly expressed in leukemic stem cells (LSCs). LSCs with high CD123 expression exhibit resistance to chemotherapy and cause the progression and recurrence of AML, so the development of therapeutic strategies targeting CD123 is underway.One therapeutic strategy targeting CD123 is CD123-specific antibody therapy. Monoclonal antibodies (mAbs) targeting CD123 have been developed, a representative example of which is tagolcimab (Tagraxofusp, SL-401). This drug is a diphtheria toxin fusion protein that targets CD123 and has been approved as a treatment for AML and BPDCN (Blastic Plasmacytoid Dendritic Cell Neoplasm). Development of CD123-targeted CAR-T cell therapy is also underway. CAR-T cell therapy, which specifically eliminates CD123-positive leukemic stem cells (LSCs), is being researched as a novel treatment aimed at curing AML. However, because CD123 is also expressed on normal hematopoietic progenitor cells, there is a need to develop technologies that enhance target selectivity. Furthermore, development of antibody-drug conjugates (ADCs) targeting CD123 is also progressing, and by combining CD123 antibodies with cytotoxic drugs, new treatment strategies for AML and MDS are being explored. Bispecific T-cell Engagers (BiTEs) that bind CD123 to CD3 on T cells are also being developed, and immunotherapy that activates T cells to target leukemic cells in AML patients is being studied. Development of diagnostic technologies targeting CD123 is also progressing, and the development of imaging technologies (PET, SPECT) for CD123-expressing tumors is expected to enable the diagnosis of leukemia and monitoring of treatment efficacy. Furthermore, detection of CD123-positive cells by flow cytometry analysis is being utilized for the diagnosis of AML and evaluation of treatment efficacy. In this disclosure, CD123 (IL-3 receptor α) is positioned as an extremely important target molecule in the maintenance of hematopoietic stem cells, the control of leukemic stem cells, and the development of cancer treatment and diagnostic techniques. In particular, the development of new cancer treatments and improved diagnostic techniques targeting CD123 may contribute to the inhibition of progression and prevention of recurrence of AML and other hematopoietic tumors, and are expected to make a significant contribution to the medical field in the future.

[0058] As used herein, "CD90 (Thy-1)" refers to a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein involved in cell-cell interactions, signal transduction, stem cell maintenance, and immune response regulation. CD90 is expressed in neurons, fibroblasts, vascular endothelial cells, hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), and other cells, and is known to be involved in tissue repair and cancer progression. In particular, it functions as a marker for cancer stem cells (CSCs) and serves as an indicator of tumor progression and metastasis. In humans, CD90 corresponds to gene ID: 7070 and is encoded by the THY1 gene located on chromosome 11, 11q23.3. This protein has a molecular weight of approximately 25-37 kDa and is structured to be bound to the cell membrane via a GPI anchor. It has the property of freely moving on the cell membrane via the GPI anchor and can be involved in extracellular signal transduction. Under certain conditions, CD90 can be solubilized and function as a secreted form of CD90. The physiological roles of CD90 include, first, stem cell maintenance and differentiation control. It is known as a surface marker for mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) and has been shown to be involved in stem cell self-renewal and differentiation. CD90 expression levels vary depending on the differentiation state of stem cells and are regulated by specific environmental factors. Second, CD90 functions in the nervous system. It has been reported that CD90 is involved in axonal growth and neuroplasticity in neurons, affecting synapse formation and regeneration processes. Abnormal CD90 expression has been suggested to contribute to neuronal damage in neurodegenerative diseases such as Alzheimer's disease. Furthermore, CD90 is involved in regulating immune responses; it is expressed on T cells and dendritic cells (DCs) and functions as a regulator of immune signaling. Furthermore, in mesenchymal stem cells (MSCs), which have immunosuppressive functions, CD90 has been shown to regulate interactions with immune cells and contribute to inflammation suppression. In addition, CD90 is involved in the regulation of angiogenesis and fibrosis, and CD90-positive vascular endothelial cells have been shown to promote angiogenesis. On the other hand, in fibrotic diseases such as pulmonary fibrosis and liver fibrosis, CD90-positive fibroblasts may be involved in the progression of fibrosis.CD90 also plays an important role in the tumor microenvironment (TME), and its expression in cancer-associated fibroblasts (CAFs) has been shown to promote cancer cell proliferation and metastasis. Furthermore, CD90 has been reported to regulate tumor angiogenesis and promote tumor cell proliferation and invasion. CD90 as a cancer stem cell (CSC) marker is particularly important in hepatocellular carcinoma (HCC). CD90-positive liver cancer stem cells have been reported to have strong self-renewal and metastatic potential and exhibit resistance to chemotherapy. Furthermore, CD90 expression in lung cancer, esophageal cancer, prostate cancer, and other cancers indicates the presence of cancer stem cells and serves as an indicator of treatment resistance and metastasis. One therapeutic strategy targeting CD90 is CD90-specific antibody therapy. Monoclonal antibodies (mAbs) targeting CD90 have been developed, and their application as immunotherapy for selectively eliminating cancer stem cells is expected. CD90-targeted CAR-T cell therapy, which aims to specifically eliminate CD90-positive cancer stem cells, is also being investigated as a novel treatment, particularly for hepatocellular carcinoma and lung cancer. Furthermore, development of anti-fibrotic therapies targeting CD90 is also progressing, and new therapeutic strategies for suppressing the progression of pulmonary and liver fibrosis by targeting CD90-positive fibroblasts are being investigated. Development of diagnostic technologies targeting CD90 is also underway, and it is expected that imaging techniques (PET, SPECT) of CD90-expressing tumors will improve diagnostic accuracy. Furthermore, detection of CD90 expression in circulating tumor cell (CTC) analysis may be used to monitor cancer progression and treatment efficacy. In the present disclosure, CD90 (Thy-1) is positioned as an extremely important target molecule in the maintenance of stem cells, the control of cancer stem cells, the treatment of fibrotic diseases, and the development of cancer treatment and diagnostic techniques. In particular, the development of new cancer treatments and anti-fibrotic treatments targeting CD90, as well as improvements in diagnostic techniques, may contribute to the suppression of cancer progression and prevention of recurrence, and the suppression of the progression of fibrotic diseases, and is expected to make a significant contribution to the medical field in the future.

[0059] As used herein, "EGFR / Her2 / neu" refers to a receptor tyrosine kinase belonging to the HER family (ERBB family) that is involved in cell proliferation, differentiation, apoptosis suppression, and the like. The HER family includes EGFR (ERBB1), HER2 / neu (ERBB2), HER3 (ERBB3), and HER4 (ERBB4), each of which has a different function but plays an important role in cancer cells. EGFR (ERBB1, Gene ID: 1956) binds to ligands such as epidermal growth factor (EGF) and activates the RAS-RAF-MEK-ERK pathway and the PI3K-AKT-mTOR pathway through autophosphorylation, thereby promoting cell proliferation and survival. On the other hand, abnormal activation of EGFR has been reported in non-small cell lung cancer (NSCLC), glioblastoma (GBM), colon cancer, and other cancers, and molecular targeted therapy targeting EGFR tyrosine kinase inhibitors (TKIs) has been clinically applied. HER2 / neu (ERBB2, Gene ID: 2064) has no clear ligand, but is activated by forming heterodimers with other HER family receptors. Its overexpression has been confirmed in breast cancer, gastric cancer, ovarian cancer, and other cancers and is known to be a poor prognostic factor. Therefore, antibody drugs targeting HER2 / neu, such as trastuzumab and pertuzumab, as well as antibody-drug conjugates (ADCs), are used for treatment. HER3 (ERBB3, Gene ID: 2065), unlike other HER family members, has extremely low tyrosine kinase activity. However, it promotes cancer cell proliferation by activating the PI3K-AKT pathway through heterodimer formation with HER2. High expression has been observed in breast cancer and prostate cancer in particular, suggesting its possible involvement in the acquisition of resistance to HER2-targeted therapies. HER4 (ERBB4, Gene ID: 2066) has the most diverse ligand binding capabilities of the HER family and is involved in the growth and differentiation of normal tissues. However, its role in cancer cells is less clear than that of HER2 and EGFR, and although its expression has been reported in breast cancer and glioma, its detailed function remains largely unknown. HER family receptors do not transmit signals alone, but rather function by forming homodimers or heterodimers with other receptors.In particular, EGFR and HER2 heterodimers have been reported to emit stronger signals than EGFR homodimers, contributing to tumor growth and therapeutic resistance through sustained tyrosine kinase activity. HER2 is thought to prolong the duration of EGFR signaling by inhibiting EGFR endocytosis, thereby promoting tumorigenesis. HER family receptors are considered to be a type of marker for cancer stem cell-like cells (CSC-like cells, CSCLC), and their expression has been confirmed to increase when cancer cells are exposed to specific environmental factors or stimuli. For example, in breast cancer stem cells (BCSCs), HER2 is involved in regulating stem cell maintenance and self-renewal ability, and may enhance cancer stem cell properties through interaction with EGFR. Furthermore, the expression of EGFR and HER2 has been reported to be involved in the tumorigenicity and acquisition of chemotherapy resistance of cancer stem cells, and it has been suggested that the formation of EGFR / HER2 heterodimers in particular may contribute to the maintenance of cancer stem cells. As used herein, "EGFR / Her2 / neu" refers collectively to receptor tyrosine kinases belonging to the HER family (ERBB family), which are considered to be important factors involved in cancer cell proliferation, metastasis, and therapeutic resistance. They are also attracting attention as markers for cancer stem-like cells (CSCLC) and cancer stem cells (CSCs). Targeting the expression and function of these receptors may provide a new strategy for cancer treatment.

[0060] As used herein, "Claudin18.2" refers to a transmembrane protein that constitutes tight junctions and is encoded by the human CLDN18 gene (Gene ID: 51208). Tight junctions form tight junctions between epithelial and endothelial cells and play a role in regulating intercellular permeability. The CLDN18 gene produces two isoforms, Claudin18.1 and Claudin18.2, through alternative splicing. These isoforms differ in 69 amino acid residues at the N-terminus. In normal tissues, Claudin18.2 is expressed primarily in differentiated gastric mucosal epithelial cells, with extremely low expression in other normal tissues. However, abnormal expression has been reported in various malignant tumors, including gastric cancer, pancreatic cancer, esophageal cancer, ovarian cancer, and lung cancer. In these cancer tissues, disruption of cell polarity exposes Claudin18.2 to the cell surface, allowing it to be recognized by immune cells. Taking advantage of this property, new therapies targeting Claudin18.2 are being developed. For example, zolbetuximab, a monoclonal antibody against Claudin18.2, has shown promising results in the treatment of advanced gastric cancer and gastroesophageal junction cancer. Furthermore, chimeric antigen receptor T cell (CAR-T cell) therapy targeting Claudin18.2 has also been developed, and promising results have been reported in phase I clinical trials for patients with gastrointestinal cancer. Thus, Claudin18.2 is attracting attention as a new therapeutic target. Claudin18.2 has also been recognized as a marker for cancer stem cell-like cells (CSC-like cells, CSCLC). It is known that Claudin18.2 expression increases when cancer cells acquire stem cell-like properties due to specific environmental factors or stimuli. For example, high expression of Claudin18.2 has been reported in pancreatic cancer, and it has been used to identify and capture cancer stem cell-like cells. However, there is currently no clear evidence that Claudin18.2 is a marker for cancer stem cells (CSCs). Therefore, although Claudin18.2 is positioned as a CSCLC marker, further research is needed to determine its role as a CSC marker.

[0061] As used herein, "Claudin6" refers to a tight junction-associated transmembrane protein encoded by the human CLDN6 gene (Gene ID: 9074). Tight junctions form tight junctions between epithelial and endothelial cells and play a role in regulating intercellular permeability. As a member of the claudin family, Claudin6 contributes to maintaining cell polarity and barrier function. Claudin6 expression is primarily limited to embryonic development and is known to be barely detectable in adult tissues. However, abnormal expression has been reported in some cancer tissues, and its expression has been suggested to be associated with tumor progression and prognosis, particularly in gastric cancer and non-small cell lung cancer (NSCLC). For example, research on gastric cancer has shown that Claudin6 functions as a marker for poor prognosis and plays a role as a tumor-promoting gene. On the other hand, it has been suggested that Claudin6 expression may suppress the malignant phenotype of breast cancer cells, and its function may vary depending on the cancer type. Furthermore, in non-small cell lung cancer, it has been reported that expression of Claudin 6 is associated with shorter survival and faster recurrence. Because Claudin 6 expression is limited in normal tissues, it has attracted attention as a new target for cancer therapy. As an example, antibody drugs targeting Claudin 6 are being developed. In particular, SAIL66, currently under development by Chugai Pharmaceutical, has shown promising results in preclinical studies as a therapeutic agent for Claudin 6-positive solid tumors. Furthermore, immunotherapy and antibody-drug conjugates (ADCs) targeting Claudin 6 are also being developed, and future clinical applications are expected. Claudin 6 is also recognized as a marker for cancer stem-like cells (CSC-like cells, CSCLC). It is known that Claudin 6 expression increases when cancer cells acquire stem cell-like properties due to specific environmental factors or stimuli. For example, research into prostate cancer and pancreatic cancer has shown that cells expressing Claudin 6 are resistant to treatment and have high invasive and metastatic potential, suggesting that it may be useful for identifying and capturing cancer stem-like cells.However, there is currently no clear evidence that Claudin 6 is a marker for cancer stem cells (CSCs). Therefore, although Claudin 6 is positioned as a CSCLC marker, further research is needed to determine whether it functions as a CSC marker.

[0062] As used herein, "FGFR (fibroblast growth factor receptor)" refers to a receptor tyrosine kinase that binds to fibroblast growth factor (FGF). By binding to extracellular FGF, it activates intracellular signal transduction and is involved in various biological processes such as cell proliferation, differentiation, migration, and survival. Four types of FGFRs have been identified in humans: FGFR1 (Gene ID: 2260), FGFR2 (Gene ID: 2263), FGFR3 (Gene ID: 2261), and FGFR4 (Gene ID: 2264), each of which plays a specific role in different tissues and cells. FGFR1 is involved in cell proliferation, differentiation, and angiogenesis, and its abnormalities are associated with skeletal dysplasia and cancer development. FGFR2 controls the growth and differentiation of epithelial cells, and genetic mutations have been reported in certain types of cancer. FGFR3 is important for bone growth and development, and mutations are associated with the development of skeletal abnormalities such as achondroplasia and bladder cancer. FGFR4 is involved in muscle and liver development and has been suggested to play a role in certain cancers. These receptors have a structure with three extracellular immunoglobulin-like domains, a transmembrane region, and an intracellular tyrosine kinase domain. Binding to FGF promotes receptor dimerization, activating downstream signaling pathways. Abnormalities in FGFR genes (mutations, amplifications, fusions, etc.) have been shown to be involved in the development and progression of various cancers. For example, FGFR3 gene mutations have been reported in 20-60% of bladder cancers, which are thought to contribute to the high proliferation rate of cancer cells. Abnormalities in FGFR have also been confirmed in various cancer types, including biliary tract cancer, breast cancer, endometrial cancer, gastric cancer, and brain tumors. Based on these findings, development of inhibitors targeting FGFR is underway. FGFR inhibitors aim to prevent cancer cell proliferation and survival by suppressing FGFR activity. In particular, the effectiveness of FGFR inhibitors has been demonstrated for patients with bladder cancer who are FGFR3 mutation-positive, and FGFR inhibitors are expected to be a new treatment option for biliary tract cancer as well.Furthermore, FGFR is also recognized as a marker for cancer stem cell-like cells (CSC-like cells, CSCLC), and it is known that FGFR expression increases when cancer cells acquire stem cell-like properties due to specific environmental factors or stimuli. However, there is currently a lack of clear evidence that FGFR is a specific marker for cancer stem cells (CSCs), and further research is needed. From the above, FGFR is an important receptor that regulates basic physiological functions of cells, and its abnormalities are deeply involved in the development and progression of cancer. Future research is expected to lead to the development of new therapies targeting FGFR and to elucidate its relationship with cancer stem cells.

[0063] As used herein, "NRP" refers to neuropilin-1, encoded by the NRP1 gene (Gene ID: 8829). Neuropilin-1 is a receptor protein present in the cell membrane that binds to ligands such as vascular endothelial growth factor (VEGF) and semaphorin (SEMA), and is involved in various biological processes such as angiogenesis, axon guidance, cell migration, and survival. In humans, the NRP1 gene is located in the p11.22 region of chromosome 10, and the encoded neuropilin-1 interacts with VEGF family members such as VEGFA and semaphorin 3A (SEMA3A), thereby controlling their signal transduction pathways. Specifically, it promotes angiogenesis by binding to VEGF and regulates axon guidance by binding to SEMA3A. Neuropilin-1 has been shown to be involved in the angiogenesis and progression of cancer, and its expression has been reported to be elevated in tumor tissues of multiple cancer patients. Its expression level correlates with the degree of metastasis, and high expression has been observed particularly in brain tumors, prostate cancer, breast cancer, colon cancer, and lung cancer. Furthermore, it has been suggested that neuropilin-1 is also involved in the immune evasion mechanism of cancer cells, contributing to the suppression of T cell responses and the formation of an immunosuppressive microenvironment. Neuropilin-1 is also known to be a marker for cancer stem cell-like cells (CSC-like cells, CSCLC). It has been reported that neuropilin-1 expression increases when cancer cells acquire stem cell-like properties in response to specific environmental factors or stresses. For example, it has been confirmed that hypoxic environments and induction of EMT (epithelial-mesenchymal transition) increase neuropilin-1 expression and result in the acquisition of a cancer stem cell-like phenotype. However, there is currently no clear evidence that neuropilin-1 is a specific marker for cancer stem cells (CSCs). Some studies suggest that neuropilin-1 expression may be involved in the maintenance and self-renewal of cancer stem cells, but further research is needed to determine whether its function is specific to CSCs. From the above, it has been shown that neuropilin-1 is an important receptor that regulates basic physiological functions of cells, and its abnormalities are deeply involved in the development and progression of cancer.In particular, its role as a marker for cancer stem cell-like cells (CSCLC) has been confirmed, and future research is expected to reveal its relationship with cancer stem cells and lead to the development of new cancer treatments targeting neuropilin 1.

[0064] As used herein, "c-Met" refers to a receptor tyrosine kinase encoded by the MET gene (Gene ID: 4233), also known as the hepatocyte growth factor receptor (HGF receptor). c-Met is a cell membrane-spanning protein that is activated by binding to hepatocyte growth factor (HGF). c-Met plays an important role in physiological processes such as embryonic development, organogenesis, and wound healing. When HGF binds to c-Met, receptor dimerization and autophosphorylation are induced, activating signal transduction pathways that control cell proliferation, motility, invasiveness, morphogenesis, and other processes. However, abnormal activation of c-Met is deeply involved in the development and progression of cancer. Specifically, mutation, amplification, or overexpression of the MET gene, or the formation of an autocrine loop with HGF, can aberrantly activate c-Met signaling, which promotes tumor growth, angiogenesis, and metastasis. Abnormalities in c-Met have been observed in many human malignant tumors, particularly in cancers of the kidney, liver, stomach, breast, and brain. In these cancers, overexpression or activation of c-Met is associated with poor prognosis and high metastatic potential. Furthermore, c-Met has also been recognized as a marker for cancer stem cells (CSC-like cells, CSCLC). It is known that c-Met expression increases when cancer cells acquire stem cell-like properties in response to specific environmental factors or stimuli. However, there is currently no clear evidence that c-Met is a specific marker for cancer stem cells (CSCs). While it has been suggested that c-Met expression may be involved in the maintenance and self-renewal of cancer stem cells, further research is needed to determine whether its function is specific to CSCs. Thus, c-Met is an important receptor that regulates basic cellular physiological functions, and its abnormalities are deeply involved in the development and progression of cancer. In particular, its role as a marker for cancer stem cell-like cells (CSCLC) has been confirmed, and future research is expected to reveal its relationship with cancer stem cells and lead to the development of new cancer treatments targeting c-Met.

[0065] As used herein, "OCT" refers to a group of ES cell-related markers, particularly including a group of transcription factors that maintain the undifferentiated state and self-renewal ability of pluripotent stem cells. It has been suggested that the OCT family plays an important role not only in ES cells and iPS cells, but also in cancer stem cells (CSCs) and cancer stem cell-like cells (CSCLCs). A representative example of the OCT family is OCT4 (POU5F1, Gene ID: 5460), and other POU family genes may also be involved in maintaining pluripotency and the developmental process of cells. The role of OCT is to maintain pluripotency and ensure undifferentiated state in ES cells and similar cells. OCT4 acts cooperatively with SOX2 and NANOG to control the expression of pluripotency genes and suppress differentiation-inducing signals. It has also been shown that OCT is involved in the epigenetic mechanism of maintaining pluripotency through histone modification and chromatin remodeling. In the context of cancer, abnormal expression of OCT is closely associated with cancer progression and the acquisition of therapeutic resistance. In particular, OCT4 has been reported to be highly expressed in various types of cancer stem cells (CSCs) and plays an important role in maintaining CSC self-renewal and tumorigenicity. For example, in lung adenocarcinoma, cells with high OCT4 expression have been shown to induce epithelial-mesenchymal transition (EMT), improving invasiveness and metastatic potential (Chiou et al., Cancer Research, 2010). Furthermore, OCT4-positive cancer cells exhibit resistance to conventional chemotherapy and radiotherapy, and have been shown to be a major cause of tumor recurrence after treatment. OCT also functions as a marker for cancer stem-like cells (CSCLC). It has been observed that cancer cells acquire stem cell-like properties by increasing the expression of OCT family members when adapting to stressful environments and hypoxia. For example, in breast cancer and pancreatic cancer, it has been reported that cell populations with high expression of the OCT family contribute to treatment resistance and enhanced invasion and metastasis. Furthermore, overexpression of the OCT family may be involved in tumor cell regeneration and secondary tumor formation after chemotherapy. From the perspective of cancer treatment and prevention, therapeutic strategies targeting OCT are attracting attention.Development of small molecule inhibitors that control the activity of the OCT family is underway, and attempts are being made to overcome treatment resistance by disrupting the CSC maintenance mechanism. Antibody drugs and CAR-T cell therapy are also being developed to selectively eliminate OCT-expressing cancer cells. Furthermore, it is believed that using OCT expression as a biomarker will enable cancer prognosis prediction and evaluation of treatment efficacy. Based on these findings, OCT is an important transcription factor group that maintains the undifferentiated state of ES cells and similar pluripotent stem cells, and may also play a similar function in cancer stem cells and cancer stem-like cells. In particular, OCT expression is associated with cancer malignancy and treatment resistance, raising hopes for its application as a new target for cancer therapy.

[0066] As used herein, "SOX" refers to the SRY-related HMG-box gene family, a group of transcription factors that play a central role in regulating developmental processes and cell differentiation in many species, including mammals. The SOX family consists of more than 20 genes and is classified into groups A through G based on the similarity of their amino acid sequences. These genes share a highly conserved DNA-binding domain called the HMG (High Mobility Group) box, consisting of approximately 80 amino acids, which binds to the minor groove of DNA and regulates transcription. Among the SOX family members, SOX2 is known as a transcription factor essential for maintaining the pluripotency and self-renewal of embryonic stem cells (ES cells) and neural stem cells. Together with OCT4 and NANOG, SOX2 forms a gene expression network that maintains the undifferentiated state of pluripotent stem cells and controls cell differentiation. SOX2 also plays an important role in the establishment of iPS cells and has attracted attention in the fields of regenerative medicine and cell therapy. Abnormal expression of SOX2 has been reported to contribute to the development and progression of certain cancers. Amplification of the SOX2 gene has been observed in lung cancer and esophageal squamous cell carcinoma, suggesting its role as a lineage survival oncogene in these cancers. Overexpression of SOX2 is required for cancer cell proliferation and anchorage-independent growth, contributing to tumor formation and maintenance. Furthermore, SOX2 is involved in maintaining the properties of cancer stem cells (CSCs) and may contribute to treatment resistance and recurrence. Other members of the SOX family also play important roles in various cancers. For example, SOX10 is a transcription factor involved in neural crest development and melanocyte differentiation and is a useful marker for schwannoma, neurofibroma, and melanoma. Furthermore, SOX11 is used as a diagnostic marker for mantle cell lymphoma. Expression patterns of these SOX family factors provide important information for cancer diagnosis and prognosis. Novel therapeutic strategies targeting SOX family factors are being explored for cancer treatment and prevention. For example, attempts are being made to suppress the growth of cancer cells and improve the therapeutic effect by suppressing the expression of SOX2.Furthermore, research is being conducted to realize personalized medicine by utilizing the expression status of SOX family factors as biomarkers. In summary, the SOX family is a group of transcription factors that play a central role in controlling developmental processes and cell differentiation, and their abnormal expression contributes to the development and progression of cancer. In particular, SOX2 is essential for the maintenance of pluripotent stem cells and is also involved in maintaining the properties of cancer stem cells, so it is attracting attention as a new target for cancer diagnosis and treatment. Future research is expected to lead to the development of effective cancer treatments that target SOX family factors.

[0067] As used herein, "TGF-β1" is an abbreviation for transforming growth factor beta 1 and refers to a type of cytokine belonging to the growth factor superfamily. This protein is a member of the TGF-β family and is known to be involved in a wide range of biological processes, including cell proliferation, differentiation, apoptosis, immunoregulation, and extracellular matrix formation. In humans, TGF-β1 is encoded by the TGFB1 gene and is registered as NCBI Gene ID: 7040. This gene is located on chromosome 19 (19q13.2) and functions as a secreted homodimeric protein after post-transcriptional modification. Active TGF-β1 is synthesized in the form of a precursor called l-TGF-β1 (L-TGF-β1) and converted to its mature form by proteolysis. This protein exerts its physiological functions by binding to TGF-β receptors (TGFBR1, TGFBR2) and activating the intracellular SMAD signaling pathway. TGF-β1 has diverse physiological functions and has been reported to be involved in inflammation suppression, wound healing, fibrosis induction, and tumorigenesis. In particular, it is known to promote epithelial-mesenchymal transition (EMT) and enhance the migration and invasive capabilities of cancer cells. This suggests that it contributes to the progression and metastasis of epithelial tumors. TGF-β1 has also been reported as a marker for cancer stem cell-like cells (CSCLC). CSCLC is a subpopulation of cancer cells with self-renewal and differentiation capabilities, and is thought to be involved in tumor progression and drug resistance. In particular, research on non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, etc. has suggested that TGF-β1 signaling may contribute to the maintenance of CSCLC. TGF-β1 is known as one of the signals involved in the maintenance and differentiation of cancer stem cells (CSCs), but is not considered a direct marker of CSCs.Molecules commonly recognized as CSC markers include CD44, CD133, and ALDH1. Unlike these, TGF-β1 is not specifically expressed on the surface of cancer cells, but rather functions as a factor that promotes CSC properties in the tumor microenvironment. Specifically, it has been suggested that TGF-β1 induces a stem cell-like phenotype through EMT and may contribute to the maintenance of CSCs in certain tumor environments, but it is not used alone as an indicator of CSCs. Therefore, although TGF-β1 is an important factor associated with tumor progression and treatment resistance, it is not a direct marker of CSCs; rather, it functions as part of a signaling pathway that controls the properties of CSCs.

[0068] As used herein, "ZEB2" is an abbreviation for Zinc Finger E-box Binding Homeobox 2 and refers to a type of transcription factor. This protein belongs to the ZEB family and functions to regulate gene expression by binding to the E-box sequence (5'-CANNTG-3') in DNA. In particular, it is known to be involved in regulating epithelial-mesenchymal transition (EMT) and to control cell plasticity, migration, and invasion. In humans, ZEB2 is encoded by the ZEB2 gene and is registered under NCBI Gene ID: 9839. This gene is located on chromosome 2 (2q22.3) and is composed of multiple exons. ZEB2 contains two zinc finger domains and an SMAD-binding domain (SBD) and interacts with the TGF-β signaling pathway, thereby regulating cell differentiation and gene expression. One of ZEB2's main functions is induction of EMT, a process in which epithelial cells acquire mesenchymal cell characteristics and is involved in development, wound healing, fibrosis, and cancer metastasis. ZEB2 promotes EMT by binding to the promoter region of the gene encoding E-cadherin (CDH1) and suppressing its expression. This reduces cell-cell adhesion and increases migration and invasion. Furthermore, ZEB2 has been reported to be involved in immune responses and the acquisition of drug resistance in the tumor microenvironment. In particular, its function downstream of TGF-β signaling has been suggested to enhance the invasive and metastatic potential of cancer cells and contribute to the acquisition of resistance to chemotherapy and targeted therapies. Furthermore, ZEB2 has also been reported as a marker for cancer stem cell-like cells (CSCLC). CSCLC is a subpopulation of cancer cells involved in tumor self-renewal and drug resistance, and it has been suggested that ZEB2 expression may contribute to the maintenance of these cell populations. In particular, it has been reported that ZEB2 enhances the characteristics of CSCLC through EMT in tumors such as breast cancer, pancreatic cancer, and non-small cell lung cancer (NSCLC). However, ZEB2 is not a direct marker for cancer stem cells (CSC).While CD44, CD133, and ALDH1 are commonly used as CSC markers, it has been suggested that ZEB2 may indirectly regulate the expression of these molecules. For example, it has been reported that high ZEB2 expression enhances CSC-like properties in some cancer cells, but ZEB2 alone cannot specifically identify CSCs. Therefore, ZEB2 is an important transcription factor that regulates the plasticity and invasive ability of tumor cells through EMT and is involved in cancer progression and therapeutic resistance. However, it is not a direct CSC marker; rather, it functions as part of a signaling pathway that controls the properties of CSCs.

[0069] As used herein, "c-MET" is an abbreviation for the tyrosine kinase receptor MET (Mesenchymal-Epithelial Transition factor), and refers to a type of receptor tyrosine kinase (RTK) involved in cell proliferation, migration, invasion, angiogenesis, and survival. c-MET is a receptor that uses hepatocyte growth factor (HGF, Hepatocyte Growth Factor) as a ligand, and the HGF / c-MET signaling pathway plays an important role in developmental processes and tissue repair. In humans, c-MET is encoded by the MET gene and is registered under NCBI Gene ID: 4233. This gene is located on chromosome 7 (7q31), and after synthesis as a precursor protein, it matures as a heterodimeric protein localized in the cell membrane. The extracellular domain of c-MET binds to HGF, which induces r...

Claims

1. A composition for treating or preventing cancer, comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for FAP (fibroblast-activation protein); and B) optionally, lipid nanoparticles (LNPs).

2. The composition of claim 1, wherein the LNP comprises at least one selected from the group consisting of a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol.

3. The composition of claim 1, wherein the LNP comprises a PEGylated lipid, an ionizable lipid, a phospholipid, and cholesterol.

4. The composition of claim 1, wherein the LNP consists of ALC-0315, ALC-0159, 1,2-DSPC, and cholesterol.

5. The composition of claim 1, wherein the CAR comprises an amino acid sequence encoded by the nucleic acid sequence set forth in SEQ ID NO: 1 or a variant thereof, or an amino acid sequence set forth in SEQ ID NO: 2 or a variant thereof.

6. The composition of any one of claims 1 to 5, wherein the composition is delivered to the FAP.

7. The composition according to any one of claims 1 to 6, wherein the composition is for inducing T cells in a subject.

8. The composition according to any one of claims 1 to 7, wherein the composition is used in combination with other anti-cancer agents.

9. The composition according to claim 8, wherein the other anticancer agent is directed against a solid cancer.

10. The composition of claim 8 or 9, wherein the other anticancer agent comprises 5-FU, a PD-1 antibody, or a CTLA4 antibody.

11. A pharmaceutical kit or combination comprising: 1) an agent comprising A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for FAP, and B) optionally lipid nanoparticles (LNPs); and 2) another anticancer agent different from 1).

12. The composition according to any one of claims 1 to 10, or the pharmaceutical kit or combination according to claim 11, wherein the mRNA is administered by intravenous injection.

13. A composition for treating or preventing cancer, comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for cancer stem cells (CSCs); and B) optionally, lipid nanoparticles (LNPs).

14. A composition for treating or preventing cancer, comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for a cancer stem-like cell (CSCLC) marker; and B) optionally, a lipid nanoparticle (LNP).

15. A composition for treating or preventing cancer, comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) for an ES cell-associated marker; and B) optionally, lipid nanoparticles (LNPs).

16. A composition for treating or preventing cancer, comprising: A) mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the mRNA is at least partially methylated; and B) optionally, a lipid nanoparticle (LNP).

17. A composition for treating or preventing cancer, comprising: A) mRNA containing a nucleic acid sequence encoding a chimeric antigen receptor (CAR); and B) lipid nanoparticles (LNPs) containing polybetaine.

18. A composition for use in improving the delivery efficiency of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), comprising a lipid nanoparticle (LNP) containing polybetaine.

19. A composition for inhibiting tumor immune evasion, comprising an inhibitor of Mif and / or an inhibitor of CD74.

20. A composition for improving delivery of chimeric antigen receptor (CAR)-T cells, comprising an inhibitor targeting Mif and / or CD74, and CAR-T cells containing mRNA comprising a nucleic acid sequence encoding the CAR.

21. A composition for improving a tumor microenvironment, comprising mRNA containing a nucleic acid sequence encoding a chimeric antigen receptor (CAR).

22. A composition for suppressing tumor growth, comprising mRNA containing a nucleic acid sequence encoding a chimeric antigen receptor (CAR).

23. A composition for optimizing the immune cell composition of a tumor microenvironment, comprising mRNA containing a nucleic acid sequence encoding a chimeric antigen receptor (CAR).

24. A method for verifying the effect of mRNA containing a nucleic acid sequence encoding a chimeric antigen receptor (CAR), the method comprising: contacting the mRNA with spleen cells; and measuring the effect on the spleen cells.

25. A method for evaluating mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), the method comprising: contacting the mRNA with cancer tissue; and performing FACS analysis of the cancer tissue.

26. A method for single-cell analysis of the MIF-CD74 axis of mRNA containing a nucleic acid sequence encoding a chimeric antigen receptor (CAR), comprising: contacting the mRNA with a subject cell; and analyzing the effect on MIF and CD74 in the cell.

27. A method for assessing epitope spreading of mRNA comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), the method comprising: contacting the mRNA with MC38 tumor cells; and performing epitope analysis in the tumor cells.

Images