Anti-cancer adjuvant containing Lactobacillus plantarum strain

Abstract

The present invention relates to an anti-cancer adjuvant containing a Lactobacillus plantarum strain, and the Lactobacillus plantarum strain cells or a culture medium of the strain can overcome the resistance of cancer cells to anti-cancer drugs and increase the sensitivity of cancer cells to anti-cancer drugs. When administered in combination with conventional anti-cancer drugs, the bacteria can also improve side effects associated with the anti-cancer drugs, making them useful as anti-cancer adjuvant agents.

Description

[Technical Field]

[0001] This invention relates to an anti-cancer adjuvant containing a Lactobacillus plantarum strain. [Background technology]

[0002] The term "microbiome" is a combination of the words "microbe" and "genome," and the term "human microbiome" refers to the genomes of all microorganisms living in the human body. While various types of microorganisms are present in several parts of the human body, 70% of the human microbiome is distributed in the digestive tract, with the largest number of microorganisms residing in the large intestine. The microbiome is closely related to the human immune system and physical development, and its strong association with various diseases, including metabolic disorders such as obesity and diabetes, inflammatory bowel disease, and depression, has been consistently reported. After the initial completion of the Human Genome Project in 2002, researchers attempted to identify the relationship between genes and intractable diseases, and found that environmental factors, particularly the microbiome environment, may have a significant impact on disease. Microbiome therapeutics grow in the intestines as living organisms and affect the human body through interactions with human cells. For these reasons, they are attracting attention as innovative new drugs that can improve the low efficacy and high recurrence rates of existing drugs for intractable diseases. Furthermore, in December 2022, the US FDA approved Ferring Pharmaceuticals' REBYOTA®, the first microbiome-based treatment for Clostridium difficile infection (CDI), marking the beginning of the commercialization of microbiome therapeutics. Seres Therapeutics' SER-109 is also currently under FDA review as the first oral microbiome therapeutic.

[0003] Gastrointestinal damage and dysfunction are well-known side effects of cancer chemotherapy treatment that can be debilitating and potentially life-threatening. In particular, chemotherapy administration is often associated with mucositis, diarrhea (chemotherapy-induced diarrhea (CID)), bacterial translocation, malabsorption, abdominal cramps, gastrointestinal bleeding, and vomiting. These side effects, as a clinical consequence of structural and functional damage to the intestinal epithelium, often necessitate a reduction in the dose and frequency of chemotherapy, adversely affecting the patient's overall clinical outcome. Intestinal mucositis and diarrhea can lead to severe dehydration, electrolyte imbalance, sepsis due to bacterial translocation, cardiovascular instability, and renal failure.

[0004] In particular, chemotherapy-induced damage to the small intestinal mucosa, known as gastrointestinal mucositis, is characterized by absorption and barrier damage in the small intestine. For example, the widely used chemotherapy agents 5-fluorouracil (5-FU), irinotecan, and methotrexate are known to increase apoptosis in the rodent small intestine, leading to villous atrophy and crypt hypoplasia. Furthermore, chemotherapy agents have been shown to increase apoptosis in intestinal crypts 24 hours after administration, followed by decreases in villus area, crypt length, number of mitoses per crypt, and enterocyte height 3 days after chemotherapy. Therefore, structural changes in the small intestine can directly lead to intestinal dysfunction and, in some cases, diarrhea. This is an increasingly serious problem that, although gradually alleviated after cancer chemotherapy, is essentially untreatable once established.

[0005] Recently, combination therapy has become popular to enhance the effectiveness of disease treatment. Combination therapy involves the use of two or more drugs or methods, either simultaneously or in relatively rapid succession. The side effects of two or more therapeutic methods used in combination therapy may be additive or less than additive, but the therapeutic effects may be additive or greater than additive. When administered in combination, the effects produced by the combined administration of each component can be expected to be synergistic, greater than the sum of the effects produced when each component is administered alone. Therefore, there is a need to develop combination therapies that can synergistically increase the effects of treatment using single components. Summary of the Invention [Problem to be solved by the invention]

[0006] One aspect provides a composition for use as an adjunct to anti-cancer therapy, comprising a Lactobacillus plantarum strain, a culture of said strain, a lysate of said strain, or a mixture thereof.

[0007] Another aspect is to provide a composition for enhancing sensitivity to anticancer drugs, comprising a Lactobacillus plantarum strain, a culture of said strain, a homogenate of said strain, or a mixture thereof.

[0008] Another aspect is to provide an anti-cancer adjuvant comprising a Lactobacillus plantarum strain, a culture of said strain, a lysate of said strain, or a mixture thereof.

[0009] Another aspect provides a method for preventing or reducing side effects in a subject receiving an anticancer drug, comprising administering a Lactobacillus plantarum strain, a culture of the strain, a homogenate of the strain, or a mixture thereof to the subject receiving the anticancer drug.

[0010] Another aspect provides a use of a Lactobacillus plantarum strain, a culture of said strain, a homogenate of said strain, or a mixture thereof to prevent or reduce side effects in a subject receiving an anticancer drug.

[0011] Another aspect provides a use of a composition comprising a Lactobacillus plantarum strain, a culture of said strain, a homogenate of said strain, or a mixture thereof, for enhancing sensitivity to an anticancer drug.

[0012] Another aspect is to provide a method for increasing sensitivity to an anti-cancer drug, comprising the step of administering an effective amount of a Lactobacillus plantarum strain, a culture of said strain, a homogenate of said strain, or a composition thereof to an individual in need thereof.

[0013] Another aspect provides the use of a Lactobacillus plantarum strain, a culture of said strain, a lysate of said strain, or a composition comprising a mixture thereof for the manufacture of a pharmaceutical preparation for increasing sensitivity to anticancer drugs.

[0014] Another aspect provides an adjunctive use of a composition comprising a Lactobacillus plantarum strain, a culture of said strain, a lysate of said strain, or a mixture thereof in anti-cancer therapy.

[0015] Another aspect is to provide a method for assisting anti-cancer therapy, comprising the step of administering an effective amount of a Lactobacillus plantarum strain, a culture of said strain, a lysate of said strain, or a composition thereof to an individual in need thereof.

[0016] Another aspect provides the use of a composition comprising a Lactobacillus plantarum strain, a culture of said strain, a lysate of said strain, or a mixture thereof, for the manufacture of a pharmaceutical preparation to aid in anti-cancer treatment. [Means for solving the problem]

[0017] One aspect provides a composition for supplementing anti-cancer therapy or a composition for enhancing sensitivity to anti-cancer drugs, which comprises a strain of the genus Lactobacillus, specifically Lactobacillus plantarum GB104 strain, as an active ingredient.

[0018] Lactobacillus is a gram-positive, aerobic or facultatively anaerobic bacillus that is widely distributed in nature. Examples of Lactobacillus include Lactobacillus plantarum and Lactobacillus sakei. The present inventors conducted research to develop new strains with excellent anti-cancer effects and selected Lactobacillus plantarum GB104 as a candidate anti-cancer strain. This strain was deposited at the Korea Institute of Bioscience and Biotechnology (KIBIT) Biological Resources Center on January 14, 2020, under accession number KCTC14107BP. This strain is a probiotic strain and is harmless to the human body, allowing it to be used without side effects.

[0019] The Lactobacillus species has been renamed Limosilacto bacillus or Lactiplantibacillus, and the modified strain names can be used interchangeably herein. For example, Lactobacillus plantarum has been renamed Lactiplantibacillus plantarum.

[0020] As used herein, the term "Lactobacillus plantarum GB104" may refer to the L. Plantarum GB104 strain or the Lactobacillus plantarum GB104 strain (accession number: KCTC14107BP).

[0021] In one embodiment, the strain can be the strain deposited under accession number KCTC14107BP.

[0022] In one embodiment, the strain may be a strain containing a 16S rRNA gene consisting of the nucleotide sequence of SEQ ID NO:1.

[0023] In one embodiment, the strain may have a 16S rRNA consisting of the nucleotide sequence of SEQ ID NO: 1, or a nucleotide sequence that has 97% or more identity thereto, specifically at least 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.8%, 99.9%, or 100% identity to the nucleotide sequence of SEQ ID NO: 1 herein.

[0024] In one embodiment, the strain may comprise a mutation of a naturally occurring Lactobacillus plantarum strain.

[0025] In one embodiment, the strain may be a live cell, a killed cell, or a cytoplasmic fraction obtained by disrupting the strain, preferably a live cell.

[0026] As used herein, the term "culture" can be used interchangeably with "culture supernatant," "culture supernatant," "conditioned medium," or "conditioned medium," and can refer to the entire medium containing the Lactobacillus strain, its metabolites, and additional nutrients, obtained by culturing the strain for a certain period of time in a medium that can provide nutrients so that the strain can grow and survive in vitro. The culture refers to the product obtained by culturing a probiotic strain in a known medium, and the product may or may not contain the strain itself. The medium can be selected from known liquid or solid media, such as, but not limited to, MRS liquid medium, GAM liquid medium, MRS agar medium, GAM agar medium, and BL agar medium.

[0027] The term "lysate" as used herein may be used interchangeably with "lysate" to refer to a solution or suspension of broken down microbial cells, such as Lactobacillus plantarum, in an aqueous medium. Cell lysates contain macromolecules, such as DNA, RNA, proteins, peptides, carbohydrates, lipids, and / or micromolecules, such as amino acids, sugars, fatty acids, or fractions thereof. Additionally, the lysate contains cellular debris, which may be smooth or granular in structure.

[0028] The culture medium may include the culture medium itself obtained by culturing the strain, a concentrate thereof, or a freeze-dried product thereof, or a culture supernatant obtained by removing the strain from the culture medium, or a concentrate or freeze-dried product thereof.

[0029] The culture medium may be obtained by culturing Lactobacillus plantarum in an appropriate medium (e.g., MRS plate medium) at a temperature above 10°C or below 40°C for a certain period of time, for example, 4 to 50 hours.

[0030] In one embodiment, the bacterial strain may upregulate the expression of tight junctions in intestinal tissue, specifically, the bacterial strain may upregulate the expression of one or more tight junctions selected from the group consisting of claudin-1, claudin-2, claudin-4, claudin-5, ZO-1 (Zonula Occludens), and occludin in intestinal tissue.

[0031] In one embodiment, the strain may be for reducing, ameliorating, preventing or treating side effects caused by anti-cancer drugs.

[0032] The bacterial strains of the present invention or mixtures containing them may be used to reduce the toxicity of a wide range of anti-cancer agents (e.g., chemotherapeutic agents) or associated chemotherapy treatments. While some anti-cancer agents or chemotherapeutics are known to cause chemotherapy-induced diarrhea and damage the gastrointestinal mucosa, the present invention may also be used to reduce the subclinical occurrence of CID or gastrointestinal mucosal damage from virtually all anti-cancer agents or chemotherapeutics.

[0033] As used herein, the term "sensitivity to anticancer drugs" refers to the degree to which cancer cells respond to anticancer drugs. This refers to the reduced therapeutic effect of anticancer drugs on cancer cells that have developed resistance to anticancer drugs, which reduces their effectiveness through repeated administration. When used in combination with Lactobacillus plantarum strains, the activity of anticancer drugs against anticancer drug-resistant cancers can be further enhanced.

[0034] In the present invention, the term "reduce" means any action that reduces the side effects of anticancer drugs by administering an anticancer adjuvant, and the term "improvement" in the present invention means any action that reduces the side effects of anticancer drugs by administering an anticancer adjuvant or improves or favorably changes the symptoms of cancer due to the reduction in the side effects of anticancer drugs.

[0035] As used herein, "treat" refers to any form of treatment or prevention that provides a benefit to an individual suffering from or at risk of developing a disease, including improving the individual's condition (e.g., one or more symptoms), delaying disease progression, delaying the onset of symptoms, or slowing the progression of symptoms, etc. Thus, the term "treatment" also includes prophylactic treatment of an individual to prevent the onset of symptoms.

[0036] As used herein, the terms "treatment" and "prevention" are not intended to mean a cure or complete elimination of symptoms. They refer to any form of treatment that provides a benefit to a patient suffering from a disease, including an improvement in the patient's condition (e.g., one or more symptoms), a delay in the progression of the disease, etc.

[0037] As used herein, the term "therapeutically effective amount" refers to an amount sufficient to produce a desired effect in a patient suffering from cancer, including alleviating side effects of anti-cancer treatment, ameliorating the condition (e.g., one or more symptoms), delaying the progression of disease, etc.

[0038] As used herein, the term "cancer" refers to a physiological condition in animals that is typically characterized by abnormal or uncontrolled cell growth. Cancer and cancer pathology can be associated with, for example, metastasis, interference with normally functioning surrounding cells, release of abnormal levels of cytokines or other secretory products, suppression or augmentation of inflammatory or immunological responses, neoplasia, premalignancy, malignancy, invasion of surrounding or distant tissues or organs, e.g., lymph node invasion, etc.

[0039] The cancer can be a gastrointestinal cancer or a non-gastrointestinal cancer.

[0040] The gastrointestinal cancer is a malignant tumor occurring in the gastrointestinal tract, such as the esophagus, stomach, small intestine, or large intestine. The gastrointestinal cancer may be, for example, one or more cancers selected from the group consisting of esophageal cancer, gallbladder cancer, liver cancer, biliary tract cancer, pancreatic cancer, stomach cancer, small intestine cancer, large intestine cancer, colon cancer, anal cancer, and rectal cancer, but is not limited to these. In one example, the gastrointestinal cancer may be large intestine cancer.

[0041] The non-gastrointestinal cancer includes, without limitation, malignant tumors occurring in organs other than the gastrointestinal tract or digestive system, and may be, for example, but not limited to, leukemia, acute myeloid leukemia, neuroblastoma, retinoblastoma, lung cancer, head and neck cancer, salivary gland cancer, melanoma, laryngeal cancer, prostate cancer, breast cancer, bladder cancer, kidney cancer, multiple myeloma, cervical cancer, thyroid cancer, ovarian cancer, urethral cancer, skin cancer, osteosarcoma, glioblastoma, brain tumor, or lymphoma.

[0042] In one embodiment of the present invention, the cancer may be colorectal cancer, which includes malignant tumors occurring in one or more sites selected from the group consisting of the ascending colon, transverse colon, descending colon, sigmoid colon, and rectal mucosa, and may be one or more types selected from the group consisting of adenocarcinoma, lymphoma, malignant breast carcinoma, leiomyosarcoma, Kaposi's sarcoma, and squamous cell carcinoma, but is not limited to these.

[0043] The anti-cancer agent may be selected from the group consisting of a chemo-anti-cancer agent for chemotherapy, a targeted anti-cancer agent, an immuno-anti-cancer agent, and a combination thereof, which are conventional treatments that can be used in combination.

[0044] As used herein, the term "chemo-anticancer agent" is also referred to as an antitumor drug (anti-cancer agent) or a cytotoxic drug (cytotoxic agent). It is a general term for drugs that exhibit anti-cancer activity by acting directly on DNA to block the replication, transcription, and translation processes of DNA, or by interfering with the synthesis of nucleic acid precursors in metabolic pathways, thereby inhibiting cell division. Antitumor drugs exhibit cytotoxicity by acting not only on tumor cells but also on normal cells. Chemo-anticancer agents may be used for maintenance therapy. Furthermore, as used herein, the term "maintenance therapy" refers to a treatment method in which drugs are used to treat cancer after initial anti-cancer therapy, with the aim of preventing or delaying cancer recurrence.

[0045] Specifically, the anticancer chemotherapy agent may be any one selected from the group consisting of alkylating agents, microtubule inhibitors, antimetabolites, and topoisomerase inhibitors. The alkylating agent may be any one selected from the group consisting of mechlorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil, thiotepa, altretamine, procarbazine, busulfan, streptozotocin, carmustine, lomustine, dacarbazine, cisplatin, carboplatin, and oxaliplatin. The microtubule inhibitor may be any one selected from the group consisting of docetaxel, velban, oncovin, and navelbine. The antimetabolite may be any one selected from the group consisting of fluorouracil, capecitabine, cytarabine, gemcitabine, fludarabine, ethotrexate, pemetrexed, and mercatopurine. The topoisomerase inhibitor may be any one selected from the group consisting of Hycamtin, Camptosar, Vepesid, Paclitaxel, Blenoxane, Adriamycin, and Cerubidine.

[0046] As used herein, the term "targeted anticancer drug" refers to a therapeutic agent that specifically kills cancer cells by targeting specific proteins or specific genetic alterations that are abundant only in cancer cells and blocking signals involved in the growth and development of cancer. Targeted anticancer drugs are classified into monoclonal antibodies that react extracellularly and small molecule substances that act intracellularly. Monoclonal antibodies are anticancer drugs that block cancer cell-inducing signals transmitted extracellularly and act on initiating signals related to proliferation, death, etc., while small molecule substances act on complex signal transduction that occurs intracellularly.

[0047] Specifically, the target protein may be EGFR, VEGFR, CD20, CD38, RNAK-L, BTK, Bcr-abl, PDGFR / FGFR family, MEK / RAF, HER2 / Neu, ubiquitin, JAK, MAP2K, ALK, PARP, TGFβRI, Proteasome, Bcl-2, c-Met, VR1, VR2, VR3, c-kit, AXL, RET, Braf, DNMT, CDK4 / 6, STING, or the like.

[0048] As used herein, the term "immune anticancer agent" refers to a substance that inhibits the activity of immune checkpoint proteins, which suppress the differentiation, proliferation, and activity of immune cells. It is known that this prevents cancer cells from evading the immune system, thereby eliminating cancer cells. The immunoanticancer agent may be any antibody selected from the group consisting of anti-CTLA-4 antibody, anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, anti-B7-H4 antibody, anti-HVEM antibody, anti-TIM3 antibody, anti-GAL9 antibody, anti-LAG3 antibody, anti-VISTA antibody, anti-KIR antibody, anti-BTLA antibody, and anti-TIGIT antibody. Specific examples of the immunoanticancer agent include, but are not limited to, ipilimumab, pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, and durvalumab.

[0049] In one embodiment, the anticancer chemotherapy agent may be any one or combination selected from the group consisting of, but not limited to, mechlorethamine, chlorambucil, ifosfamide, melphalan, chlorambucil, thiotepa, altretamine, procabazine, busulfan, streptozocin, camstin, lomustine, dacabazine, cisplatin, carboplatin, oxaliplatin, docetaxel, velban, Oncovin, navelbine, 5-fluorouracil, capecitabine, cytarabine, gemcitabine, fludarabine, methotrexate, pemetrexed, mercaptopurine, hycamtin, irinotecan, camptosar, porinic acid, leucovorin, bepcid, paclitaxel, blenoxane, adriamycin, cerbidine, trifluridine / tipiracil, and regorafenib. Specifically, the anti-cancer drug may be irinotecan.

[0050] In one embodiment, the chemotherapeutic agent is mechlorethamine, cyclophosphamide, chlorambucil, ifosfamide, melphalan, thiotepa, altretamine, procabazine, busulfan, streptozocin, carmustine, Lomustine, Dacarbazine, Cisplatin, Carboplatin, Oxaliplatin, Vinblastine, Vincristine, Vinorelbine, Fluorouracil (5-FU), Capecitabine, Cytarabine, Gemcitabine, Fludarabine, Methotrexate, Pemetrexed, Mercaptopurine (6-MP), Topotecan, Irinotecan, Etoposide, Paclitaxel, Docetaxel, Etoposide, Dactinomycin, Doxorubicin , Daunorubicin, Mitomycin, Bleomycin, Blenoxane, Bevacizumab, Cetuximab, Rituximab, Trastuzumab, Panitumumab, Aflibercept, Ramucirumab, Pembrolizumab, Nivolumab,Atezolizumab, durvalumab, avelumab, ipilimumab, gefitinib, erlotinib, osimertinib, lazertinib, afatinib, crizotinib, alectinib, brigatinib, sorafenib, sunitinib, pazopanib, lenvatinib ), Axitinib, Cabozantinib, Imatinib, Dasatinib, Nilotinib, Midostaurin, Palbociclib, Ribociclib, Abemaciclib, Olaparib, Trifluridine / tipiracil, and Regorafenib, or a combination thereof, but is not limited to these.

[0051] In one embodiment, the targeted anti-cancer agent is abciximab, adalimumab, basiliximab, bezlotoxumab, canakinumab, daclizumab, denosumab, efalizumab, golimumab, infliximab, natalizumab, olaratumab, The compound may be any one or a combination selected from the group consisting of omalizumab, palivizumab, panitumumab, trastuzumab, pertuzumab, aflibercept, ramucirumab, cetuximab, rituximab, tocilizumab, secukinumab, ustekinumab, bevacizumab, avelumab, CDNs, SB11285, and DMXAA, but is not limited to these.

[0052] In one embodiment, the immunosuppressant is atezolizumab, aveloumab, durvalumab, nivolumab, pembrolizumab, abagovomab, adecatumumab, atezolizumab, afutuzumab, alemtuzumab, anatumomab-mafenatox, apolizumab, blinatumomab, BMS-936559, catumaxomab, cemiplimab, epacadostat, epratuzumab, indoxamod, inotuzumab, ozogamicin, intelumumab, pembrolizumab, ipilimumab, isatuximab, lambrolizumab, MED The therapeutic agent may be any one or combination selected from the group consisting of, but not limited to, 14736, MPDL3280A, obinutuzumab, ocaratu- zumab, ofatumumab, olaratumab, pidilizumab, rituximab, ticilimumab, samalizumab, and tremelimumab.

[0053] In one embodiment, the side effects of the anticancer drug may be selected from the group consisting of vomiting, oral mucositis, colitis, ulcerative colitis, diarrhea, diarrhea due to enteritis, constipation, esophagitis, bleeding, hair loss, infection, fever, thrombocytopenia, anemia, abdominal pain, peripheral neurotoxicity, central neurotoxicity, muscle pain, bone pain, hypoactivity, lethargy, decreased appetite, weight loss, fatigue, decreased food intake, kidney toxicity, spleen toxicity, thymus toxicity, hepatotoxicity, cardiac toxicity, pulmonary toxicity, decreased exercise capacity, immunotoxicity, and inflammation, and may include, but are not limited to, vomiting, oral mucositis, colitis, diarrhea due to enteritis, constipation, esophagitis, hypoactivity, lethargy, decreased appetite, weight loss, fatigue, decreased food intake, and inflammation. Specifically, the anticancer drug has a mechanism for inhibiting DNA division in rapidly proliferating cells, which affects not only cancer cells but also normal cells, and therefore may cause various side effects.

[0054] In one embodiment, the bacterial strain may suppress or ameliorate side effects of anticancer drugs (e.g., chemotherapeutic drugs), specifically, anticancer drug-induced intestinal inflammatory responses or intestinal tissue damage, or anticancer drug-induced weakening or destruction of tight junctions in intestinal tissue, as well as functional disorders such as lethargy, vomiting, loss of appetite, weight loss, constipation, stomatitis, and esophagitis, which are induced by anticancer drugs.

[0055] In one embodiment of the present invention, when the Lactobacillus plantarum GB104 strain and the chemo-anticancer drug irinotecan were co-administered in tumor animal models transplanted with mouse colon cancer cell lines CT26 or MC-38, the side effects of the anticancer drug irinotecan were alleviated or improved. Specifically, the group co-administered with Lactobacillus plantarum GB104 strain showed a 50% or greater improvement in the survival rate, diarrhea, activity level, coat appearance, and posture of the mice compared to the control group of the mouse colon cancer model administered with irinotecan.

[0056] In one embodiment, in tumor animal models implanted with mouse colon cancer cell lines CT26 or MC-38, side effects induced by the chemo-anticancer drug irinotecan were observed, including decreased activity, induction of inflammatory responses in intestinal tissue, damage to intestinal tissue (e.g., intestinal crypts), and weakening or destruction of tight junctions in intestinal tissue. Therefore, intraperitoneal administration of the Lactobacillus plantarum GB104 strain before, during, and after irinotecan administration (e.g., intraperitoneal administration) was confirmed to suppress, improve, or alleviate these side effects. In particular, the levels of intestinal inflammation and tissue damage, and the expression of tight junctions in intestinal tissue were improved to the same extent as or better than those in mice in which colon cancer was not induced.

[0057] In one specific example, when the symptoms appearing as side effects in a group receiving only anticancer drugs are taken as 100% compared to a control group not receiving anticancer drugs, the Lactobacillus plantarum GB104 strain reduces side effects caused by anticancer drugs by 90% or less, 80% or less, 70% or less, 67% or less, 10-90% or less when administration is started before, simultaneously with, or after administration of anticancer drugs. %, 10-80%, 10-70%, 10-67%, 20-90%, 20-80%, 20-70%, 20-67%, 30-90%, 30-80%, 30-70%, 30-67%, 40-90%, 40-80%, 40-70%, 40-67%, 50-90%, 50-80%, 50-70%, 50-67%, or 60-67%.

[0058] The compositions of the present invention can be prepared for administration by containing at least one pharmaceutically acceptable carrier in addition to the active ingredient. The pharmaceutically acceptable carrier may be saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, liposomes, or a mixture of at least one of these components. Other common additives, such as antioxidants, buffers, and bacteriostats, may be added as needed. Furthermore, the compositions can be formulated into injection forms such as aqueous solutions, suspensions, and emulsions, as well as pills, capsules, granules, or tablets by adding diluents, dispersants, surfactants, binders, and lubricants. Target organ-specific antibodies or other ligands can be bound to the carriers to specifically act on the target organs. Furthermore, suitable formulations can be prepared according to the disease or the ingredients using methods appropriate to the art or methods disclosed in Remington's Pharmaceutical Science (latest edition), Mack Publishing Company, Easton PA.

[0059] In one embodiment, the bacterial strain and the anti-cancer agent may be administered concomitantly, sequentially or in reverse order.

[0060] As used herein, the terms "combination therapy" or "co-administration" or "in combination" refer to any form of simultaneous or concurrent treatment using at least two separate anti-cancer agents and an adjuvant anti-cancer agent. The components of the combination therapy may be administered simultaneously, sequentially, or in any order. The components may be administered in different dosages, at different administration frequencies, or via different routes as appropriate.

[0061] Specifically, the combined administration may involve simultaneous administration of the Lactobacillus plantarum strain and the anticancer drug, or administration of the Lactobacillus plantarum strain followed by administration of the anticancer drug. A combination therapy according to the present invention can be defined as providing a synergistic effect if its efficacy, measured, for example, through the degree of response, response rate, time to disease progression, or survival time, is therapeutically superior to the efficacy achieved by administering one or the other of the components of the combination therapy at a conventional dose. For example, the efficacy of a combination therapy is synergistic if its efficacy is therapeutically superior to the efficacy achieved by using each component alone. In particular, a synergistic effect is considered to exist if it does not adversely affect one or more of the degree of response, response rate, time to disease progression, or survival data, particularly the duration of response, reduces or eliminates problematic side effects compared to those occurring when each component is administered at a conventional dose, and allows for a reduction in the conventional dose of the Lactobacillus plantarum strain and the anticancer drug.

[0062] As used herein, the term "administered simultaneously" is not particularly limited and means that the components of the combination therapy are administered substantially simultaneously, for example, as an admixture or in immediately subsequent order.

[0063] As used herein, the term "sequentially administered" is not particularly limited and means that the components of a combination therapy are not administered simultaneously, but rather are administered one after the other, or together, with a specific time interval between administrations. The time interval may be the same or different between each administration of the components of the combination therapy, and may be selected from the ranges of, for example, 2 minutes to 96 hours, 1 day to 7 days, or 1 week, 2 weeks, or 3 weeks. Generally, the time interval between administrations may range from a few minutes to several hours, for example, 2 minutes to 72 hours, 30 minutes to 24 hours, or 1 to 12 hours. Additional examples include time intervals ranging from 24 to 96 hours, 12 to 36 hours, 8 to 24 hours, and 6 to 12 hours.

[0064] In one embodiment, the bacterial strain and / or anticancer agent can be administered to mammals, including humans, via various routes. The bacterial strain and / or anticancer agent may be administered via a commonly used route, such as intratumoral, intraarterial, intravenous, intravascular, intrapleural, intraperitoneal, intraorgan, intradural, intramuscular, endoscopically, intralesional, percutaneous, subcutaneous, regionally, stereotactically, orally, by direct injection, or by perfusion, specifically via oral, intravenous, or subcutaneous administration. The bacterial strain and / or anticancer agent may be administered via different routes. Specifically, the bacterial strain may be administered orally, and the anticancer agent may be administered via intraperitoneal injection.

[0065] According to one embodiment, the composition may contain 0.001% to 80% by weight of the Lactobacillus plantarum strain based on the total weight of the composition. Furthermore, the dosage of the Lactobacillus plantarum strain may be 0.01 mg to 10,000 mg, 0.1 mg to 1,000 mg, 1 mg to 100 mg, 0.01 mg to 1,000 mg, 0.01 mg to 100 mg, 0.01 mg to 10 mg, or 0.01 mg to 1 mg. The strain is included in the composition at a therapeutically or nutritionally effective amount, for example, when the strain is 10 3 ~10 16 CFU / g, 10 3 ~10 15 CFU / g, 10 3 ~10 14 CFU / g, 10 3 ~10 13 CFU / g, 10 3 ~10 12 CFU / g, 10 4 ~10 16 CFU / g, 10 4 ~10 15 CFU / g, 10 4 ~10 14 CFU / g, 10 4 ~10 13 CFU / g, 10 4 ~10 12 CFU / g, 10 5 ~10 16CFU / g, 10 5 ~10 15 CFU / g, 10 5 ~10 14 CFU / g, 10 5 ~10 13 CFU / g, 10 5 ~10 12 CFU / g, 10 6 ~10 13 CFU / g, 10 6 ~10 12 CFU / g, 10 7 ~10 13 CFU / g, 10 7 ~10 12 CFU / g, 10 8 ~10 13 CFU / g or 10 8 ~10 12 The composition may contain a CFU / g content or a culture of the same number of live or dead bacteria. Specifically, for adult patients, 1 x 10 3 ~1×10 16CFU / g of live or killed bacteria can be administered in a single dose or in divided doses. However, the dosage may vary depending on factors such as the formulation method, administration method, the patient's age, weight, sex, pathological condition, diet, administration time, administration route, excretion rate, and reaction sensitivity, and those skilled in the art can appropriately adjust the dosage taking these factors into consideration. The number of administrations may be one or more than two times within the range of clinically acceptable side effects, and the administration site may be one or more than two sites. For non-human animals, the same dosage per kg (body weight) as for humans may be administered, or the dosage may be converted based on, for example, the volume ratio (e.g., average) of organs (e.g., heart) between the target animal and humans. Possible routes of administration include oral, sublingual, parenteral (e.g., subcutaneous, intramuscular, intra-arterial, intraperitoneal, intradural, or intravenous), rectal, topical (including transdermal), inhalation, injection, or insertion of an implantable device or substance. In one embodiment, animals to be treated include humans and other mammals, and specific examples include humans, monkeys, mice, rats, rabbits, sheep, cattle, dogs, horses, pigs, etc. According to one embodiment, the composition contains a killed dried strain of bacteria, and can be administered at a dose of 1 g to 10 g, 0.5 g to 1.5 g, 2.5 g to 3.5 g, or 4.5 g to 5.5 g per dose, and may be administered once to three times per day.

[0066] Another aspect is to provide an anti-cancer adjuvant comprising a Lactobacillus plantarum strain, a culture or lysate of said strain, or an extract of said cells, culture or lysate, or a mixture thereof.

[0067] The "strain," "anticancer agent," "administration," and "combined administration" are as described above.

[0068] The individual may be an individual suffering from cancer. Furthermore, the individual may be a mammal, preferably a human.

[0069] As used herein, the term "anti-cancer therapy adjuvant" or "anti-cancer adjuvant" refers to a preparation that can improve, enhance, or increase the anti-cancer effect of an anti-cancer drug. Generally, an anti-cancer adjuvant refers to a preparation that does not exhibit anti-cancer activity by itself but can improve, enhance, or increase the anti-cancer effect of the anti-cancer drug when used in combination with the anti-cancer drug. Meanwhile, an anti-cancer adjuvant according to one embodiment has the effect of enhancing the anti-cancer activity when administered in combination with the anti-cancer drug.

[0070] The administration route, dosage, and frequency of administration of the Lactobacillus plantarum GB104 strain and the anticancer drug may be varied depending on the patient's condition and the presence or absence of side effects, and the optimal administration method, dosage, and frequency of administration can be selected within an appropriate range by a person skilled in the art. In addition, the active ingredient may be administered in combination with other drugs (e.g., the above-mentioned anticancer drugs) or physiologically active substances known to be effective in treating cancer diseases, or may be formulated as a combination formulation with other drugs.

[0071] In one embodiment, the Lactobacillus plantarum GB104 strain can be formulated as an anti-cancer adjuvant together with a pharmaceutically acceptable carrier or excipient. Specifically, the strain is combined with additional compounds effective in ameliorating or preventing the side effects of cancer chemotherapy to form a pharmaceutical composition. The formulations used in the methods of the present invention may be conveniently provided in unit dosage forms and may be prepared by methods known in the relevant art. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will vary depending on the host being treated and the particular mode of administration. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be the amount of compound that produces a therapeutic effect.

[0072] Generally, formulations can be prepared using liquid carriers, undivided solid carriers, or both, and then, if necessary, shaping the product. Pharmaceutical compositions suitable for parenteral administration can include the Lactobacillus plantarum GB104 strain in combination with one or more pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solutions, dispersions, suspensions, or emulsions, or sterile powders that can be reconstituted into sterile injectable solutions or dispersions immediately before use.

[0073] Another aspect provides a method for preventing or reducing colon damage in a subject receiving an anti-cancer drug, comprising administering to the subject a Lactobacillus plantarum strain, a culture or disruptant of said strain, or an extract of said cells, culture or disruptant, or a mixture thereof.

[0074] In one embodiment, the Lactobacillus plantarum GB104 strain and an anticancer agent (e.g., a chemical anticancer agent) are administered simultaneously, preferably for two or more days. Specifically, the administration of the strain may be initiated before the administration of the anticancer agent is started, simultaneously with the administration of the anticancer agent, or after the administration of the anticancer agent has been terminated.

[0075] The terms and methods described in relation to the above inventions are equally applicable to the inventions of pharmaceutical compositions, methods, uses, etc., unless they are inconsistent with each other. [Effects of the Invention]

[0076] The Lactobacillus plantarum strain cells or the culture medium of said strain can overcome the resistance of cancer cells to targeted anticancer drugs and increase the sensitivity of cancer cells to anticancer drugs. In addition, when administered in combination with conventional targeted anticancer drugs, they can improve the side effects associated with anticancer drugs, and can therefore be usefully used as an anticancer adjuvant. [Brief explanation of the drawings]

[0077] [Figure 1] 1 is a graph showing the activity level of mice in a mouse colon cancer (CT26) model following administration of the GB104 strain. [Figure 2] 1 is a graph showing the coat appearance of mice following administration of the GB104 strain in a mouse colon cancer (CT26) model. [Figure 3] 1 is a graph showing the severity of diarrhea in mice caused by administration of the GB104 strain in a mouse colon cancer (CT26) model. [Figure 4] 1 is a graph showing the posture of mice following administration of the GB104 strain in a mouse colon cancer (CT26) model. [Figure 5] 1 is a graph showing the survival rate of mice administered with the GB104 strain in a mouse colon cancer (CT26) model. [Figure 6] 1 is a graph showing the effect of alleviating hypoactivity (lethargy) in mice by administration of the GB104 strain in a mouse colon cancer (MC-38) model. [Figure 7] 1 is a graph showing the effect of administering the GB104 strain to alleviate inflammation and damage in the intestinal tissue of mice in a mouse colon cancer (MC-38) model. [Figure 8] 1 is a graph showing upregulation of tight junction expression in the intestinal tissue of mice by administration of the GB104 strain in a mouse colon cancer (MC-38) model. DETAILED DESCRIPTION OF THE INVENTION

[0078] Preferred examples are presented below to aid in understanding the present invention. However, the following examples are provided to facilitate understanding of the present invention, and are not intended to limit the scope of the present invention. Various modifications can be made to the examples, and the examples are not limited to the examples disclosed below and can be implemented in various forms. [Example]

[0079] Example 1. Isolation and identification of Lactobacillus plantarum GB104 strain

[0080] The isolation and identification of the Lactobacillus plantarum GB104 strain were carried out according to the methods described in Korean Patent Application Nos. 10-2020-0186738 and 10-2022-0080567, both of which are incorporated herein by reference in their entireties.

[0081] Briefly, Lactobacillus plantarum GB104 was isolated from vaginal samples of healthy women who visited a hospital for a health checkup. First, vaginal samples were collected with a cotton swab, streaked onto Rogosa SL (MRS) plates, and cultured in an anaerobic chamber at 37°C for 48 hours. Once bacterial colonies grew, single colonies were subcultured onto new MRS plates for pure isolation. After the pure isolation, the strains were cultured in MRS medium. Next, Lactobacillus plantarum GB104, which exhibited low levels of adipocyte accumulation inhibition and cytotoxicity, was selected from the cultured strains. To identify the selected Lactobacillus plantarum GB104, the 16S rRNA gene sequence obtained by PCR using primers targeting the 16S rRNA gene was analyzed by Sanger sequencing. The 16S rRNA sequence of Lactobacillus plantarum GB104 is shown in SEQ ID NO: 1. The inventors named GB104 "Lactobacillus plantarum GB104" (deposit number: KCTC 14107BP) and deposited it with the Korean Collection for Type Cultures (KCTC), Korea Institute of Biotechnology Research, on January 14, 2020. Furthermore, the strain name of Lactobacillus plantarum was changed to Lactiplantibacillus plantarum. In the following examples, the changed strain names of existing strains are used interchangeably.

[0082] Experimental Example 1. Effect of L. plantarum GB104 strain on the side effects of anti-cancer drugs in a mouse colon cancer model

[0083] We confirmed the effectiveness of L. plantarum GB104 strain in mitigating various side effects of high-dose administration of irinotecan, which is used as a first-line anticancer treatment for patients with metastatic colorectal cancer, in a CT26 colon carcinoma allograft model.

[0084] Group 1 (G1): Mice administered PBS in a mouse colon cancer model

[0085] Group 2 (G2): Mice administered GB104 alone in a mouse colon cancer model

[0086] Group 3 (G3): Mice administered irinotecan and PBS in a mouse colon cancer model

[0087] Group 4 (G4): Mice administered irinotecan and GB104 in a mouse colon cancer model

[0088] Five-week-old BALB / c mice were brought into the laboratory and, after a one-week cleansing period, the right flank area was depilated. The experiment was conducted at 6 weeks of age. BALB / c-derived colon cancer cell line CT26 was inoculated into the right flank of each mouse at a dose of 5 × 10 cells / mouse. 5 Tumor models were established by subcutaneous injection of 100 μL of cells. Tumor volume (mm ) was measured using a digital caliper. 3 )=(width 2 The size was calculated by the formula: (× length) / 2. From the time of tumor cell injection, L. plantarum GB104 strain was injected into the animal model at 1 × 10 per mouse. 9 The tumor cells were orally administered daily until the end of the study. The anticancer drug irinotecan (400 mg / kg) was intraperitoneally administered every other day on days 7, 9, and 11 after tumor cell injection.

[0089] Side effects caused by irinotecan administration were evaluated using the mouse well-being score protocol adopted by the UK Co.-ordinating Committee on Cancer Research, 1988. The specific standard table for the mouse well-being score is shown in Table 1 below. [Table 1]

[0090] The activity level of each mouse was scored according to the amount of cage movement (2 points: the animal moves normally around the environment; 1 point: the animal moves slowly or infrequently and changes its gait; 0 point: the animal is motionless and takes fewer than five steps), and the results are shown in Figure 1. The coat appearance was scored according to smoothness (2 points: healthy, smooth, and uninterrupted fur; 1 point: a slightly fluffy coat; 0 point: a very fluffy coat with visible skin and clear gaps), and the results are shown in Figure 2. The severity of diarrhea was assessed according to stool consistency scores (0: normal; 1: loose stool; 2: loose / partial diarrhea; 3: diarrhea; and 4: severe watery diarrhea), and the results are shown in Figure 3. Posture was scored as follows (2 points: normal body posture; 1 point: moderately flexed posture; 0 point: severely flexed posture), and the results are shown in Figure 4.

[0091] As shown in Figures 1 to 5, compared to G3 (PBS + Irinotecan), G4 (GB104 + Irinotecan) was confirmed to alleviate various side effects, such as decreased activity and diarrhea, in mice caused by administration of high concentrations of irinotecan, thereby contributing to improved survival rates.

[0092] Experimental Example 2. (Effect of L. plantarum GB104 strain on the alleviation of lethargy (hypoactivity) in a chemotherapy-induced diarrhea (CID) mouse colon cancer model.)

[0093] The effect of L. plantarum GB104 strain in alleviating lethargy (decreased activity) was confirmed in a mouse colon cancer model with chemotherapy-induced diarrhea (CID) caused by high-dose irinotecan administration.

[0094] Five-week-old c57BL / 6 mice were introduced into the laboratory and, after a one-week purification period, the right flank area was depilated. The experiment was conducted at 6 weeks of age. MC-38, a colon cancer cell line derived from c57BL / 6, was inoculated into the right flank of each mouse at a dose of 2 × 10 cells / mouse. 5 Tumor models were established by subcutaneous injection of 100 μL of cells. Tumor volume (mm ) was measured using a digital caliper. 3 )=(width 2 The size of the tumor was calculated by the formula: × length) / 2. On the 5th day after tumor cell injection, the tumor size was 10-30 mm. 3 Only mice falling within the range were selected, and each group was randomly set up and test groups were constructed in the same manner as in Experimental Example 1. Then, L. plantarum GB104 strain was added to the animal model at 1 × 10 per mouse. 9 CFU were orally administered daily from day 5 until just before the end of the study. The anticancer drug irinotecan (200 mg / kg) was administered intraperitoneally on days 9, 11, and 13 after tumor cell injection. To confirm the effect of L. plantarum GB104 on lethargy, a side effect caused by high-dose irinotecan administration, the movement of mice in each group was analyzed by video tracking using the Ethovision XT program, and the results are shown in Figure 6.

[0095] As shown in Figure 6, the lethargy and decreased activity of mice caused by administration of high concentrations of irinotecan, which was observed in the negative control group (PBS + Irinotecan), was alleviated in the experimental group (GB104 + Irinotecan).

[0096] Experimental Example 3. Alleviation of colon tissue damage caused by administration of high-dose irinotecan from L. plantarum GB104 strain

[0097] We investigated the effect of L. plantarum GB104 strain in alleviating intestinal tissue damage in a mouse colon cancer model with chemotherapy-induced diarrhea (CID) caused by high-dose irinotecan administration.

[0098] Colon tissues from chemotherapy-induced diarrhea (CID) mice with colon cancer in Experimental Example 2 were excised 19 days after tumor cell injection and fixed in 10% formalin. Then, paraffin blocks were prepared and sliced ​​to a thickness of 4 μm to prepare slides. Changes in the colon tissues were confirmed by hematoxylin and eosin (H&E) staining, and the results are shown in Figure 7.

[0099] As shown in Figure 7, significant damage to the intestinal crypts was observed in the negative control group (PBS + Irinotecan) due to the administration of high-concentration irinotecan, but an inflammatory response in the intestinal tissue and alleviation of colonic tissue damage were confirmed in the experimental group (GB104 + Irinotecan) administered with L. plantarum GB104.

[0100] Experimental Example 4. Enhancement of intestinal tight junctions by administration of high-dose irinotecan from L. plantarum GB104 strain

[0101] We investigated the effect of L. plantarum GB104 strain in strengthening tight junctions in colonic tissue in a mouse colon cancer model with chemotherapy-induced diarrhea (CID) induced by high-dose irinotecan.

[0102] Five-week-old c57BL / 6 mice were introduced into the laboratory and, after a one-week purification period, the right flank area was depilated. The experiment was conducted at 6 weeks of age. MC-38, a colon cancer cell line derived from c57BL / 6, was inoculated into the right flank of each mouse at a dose of 2 × 10 cells / mouse. 5Tumor models were established by subcutaneous injection of 100 μL of cells. Tumor volume (mm ) was measured using a digital caliper. 3 )=(width 2 The size of the tumor was calculated by the formula: × length) / 2. On the 5th day after tumor cell injection, the tumor size was 10-30 mm. 3 Only mice falling within the range were selected, and each group was randomly set up and test groups were constructed in the same manner as in Experimental Example 1. Then, L. plantarum GB104 strain was added to the animal model at 1 × 10 per mouse. 9 CFU were orally administered daily from day 5 until just before the end of the study. The anticancer drug irinotecan (50 mg / kg) was administered intraperitoneally on days 9, 11, 13, 15, and 17 after tumor cell injection. On day 19 after tumor cell injection, colon tissue was excised and disrupted, RNA was isolated, and cDNA was synthesized. The mRNA expression levels of tight junction-related genes (ZO-1, Occludin, Claudin-2) were then determined using the QuantStudio 3 Real-Time PCR Instrument. The results are shown in Figure 8.

[0103] As shown in Figure 8, the mRNA expression levels of tight junction-related genes were significantly increased in the experimental group (GB104 + Irinotecan) compared to the negative control group (PBS + Irinotecan). This confirmed that the L. plantarum GB104 strain can alleviate the side effects of high-concentration anticancer drugs, which damage intestinal epithelial cells, increasing permeability and weakening barrier junctions.

[0104] The above description of the present invention is for illustrative purposes only, and those skilled in the art will understand that the present invention can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. Therefore, it should be understood that the above-described embodiments are illustrative in all respects and are not limiting.

[0105] [Accession number]

[0106] Depository institution name: Korea Institute of Bioscience and Biotechnology

[0107] Accession number: KCTC14107BP

[0108] Date of acceptance: 20200114 TIFF2026507666000003.tif226170

Claims

1. A composition for use as an adjunct to anti-cancer therapy, comprising a Lactobacillus plantarum strain, a culture of said strain, a disrupted product of said strain, or a mixture thereof.

2. The composition according to claim 1, which is for reducing, ameliorating, preventing or treating side effects caused by anticancer drugs.

3. The composition of claim 1 , wherein the strain comprises a 16S rRNA sequence of SEQ ID NO:

1.

4. The composition of claim 1 , wherein the strain is the strain deposited under accession number KCTC14107BP.

5. 2. The composition of claim 1, wherein the strain comprises a mutation of a naturally occurring Lactobacillus plantarum strain.

6. The composition according to claim 2 , wherein the anticancer agent is any one selected from the group consisting of a chemical anticancer agent, a targeted anticancer agent, and an immune anticancer agent.

7. The anticancer drugs include mechlorethamine, cyclophosphamide, chlorambucil, ifosfamide, melphalan, thiotepa, altretamine, procabazine, busulfan, streptozocin, carmustine, and lomustine. e), Dacarbazine, Cisplatin, Carboplatin, Oxaliplatin, Vinblastine, Vincristine, Vinorelbine, Fluorouracil (5-FU), Capecitabine, Cytarabine, Gemcitabine, Fludarabine ne), methotrexate, pemetrexed, mercaptopurine (6-MP), topotecan, irinotecan, etoposide, paclitaxel, docetaxel, etoposide, dactinomycin, doxorubicin, daunorubicin in), mitomycin, bleomycin, blenoxane, bevacizumab, cetuximab, rituximab, trastuzumab, panitumumab, aflibercept, ramucirumab, pembrolizumab, nivolumab, atezolizumab,Durvalumab (Duvalumab), Avelumab (Avelumab), Ipilimumab (Ipilimumab), Gefitinib (Gefitinib), Erlotinib (Erlotinib), Osimertinib (Osimertinib), Lazertinib (Lazertinib), Afatinib (Afatinib), Crizotinib (Crizotinib), Alectinib (Alectinib), Brigatinib (Brigatinib), Sorafenib (Sorafenib), Sunitinib, pazopanib, lenvatinib, axitinib, cabozantinib, imatinib, dasatinib, nilotinib, midostaurin, palbociclip The composition of claim 6, which is any one or combination selected from the group consisting of palbociclib, ribociclib, abemaciclib, olaparib, trifluridine / tipiracil, and regorafenib.

8. 3. The composition of claim 2, wherein the side effects are selected from the group consisting of vomiting, oral mucositis, colitis, ulcerative colitis, diarrhea, diarrhea due to enteritis, constipation, esophagitis, bleeding, hair loss, infection, fever, thrombocytopenia, anemia, abdominal pain, peripheral neurotoxicity, central neurotoxicity, muscle pain, bone pain, hypoactivity, asthenia, decreased appetite, weight loss, fatigue, decreased food intake, kidney toxicity, spleen toxicity, thymus toxicity, liver toxicity, cardiac toxicity, lung toxicity, decreased exercise capacity, immunotoxicity, and inflammation.

9. The composition of claim 1, wherein the cancer is any one selected from the group consisting of gastric cancer, colorectal cancer, pancreatic cancer, gallbladder cancer, biliary tract cancer, thyroid cancer, salivary gland cancer, esophageal cancer, head and neck cancer, small intestine cancer, anal cancer, colon cancer, rectal cancer, lung cancer, kidney cancer, breast cancer, and lymphoma.

10. The composition of claim 1 , wherein the strain upregulates the expression of tight junctions in intestinal tissue.

11. The composition of claim 1 , wherein the bacterial strain suppresses intestinal inflammatory responses or intestinal tissue damage induced by anti-cancer drugs.

12. The composition according to claim 1 or 2, wherein the bacterial strain and the anti-cancer agent are administered in combination simultaneously, sequentially or in reverse order.

13. The composition of claim 1 or 2, wherein the bacterial strain and anti-cancer agent are administered orally, intravenously, or subcutaneously.

14. The composition of claim 1 or 2, wherein the bacterial strain is administered orally and the anti-cancer agent is administered subcutaneously.

15. A composition for enhancing sensitivity to anticancer drugs, comprising a Lactobacillus plantarum strain, a culture of said strain, a disrupted product of said strain, or a mixture thereof.

16. An anti-cancer adjuvant comprising a Lactobacillus plantarum strain, a culture of said strain, a disrupted product of said strain, or a mixture thereof.

17. A method for preventing or reducing colon damage in a subject receiving an anticancer drug, comprising administering a Lactobacillus plantarum strain, a culture of said strain, a disrupted product of said strain, or a mixture thereof to said subject.

18. 18. The method of claim 17, wherein administration of the bacterial strain is initiated before administration of an anti-cancer agent.

19. 18. The method of claim 17, wherein administration of the bacterial strain is initiated during administration of an anti-cancer agent.

20. 18. The method of claim 17, wherein administration of the bacterial strain is initiated after administration of an anti-cancer agent has been completed.

21. 1. Use of a composition comprising a Lactobacillus plantarum strain, a culture of said strain, a lysate of said strain, or a mixture thereof as an adjunct to anti-cancer therapy.

22. A method for assisting anti-cancer therapy, comprising the step of administering an effective amount of a Lactobacillus plantarum strain, a culture of said strain, a lysate of said strain, or a composition thereof to an individual in need thereof.

23. 1. Use of a composition comprising a Lactobacillus plantarum strain, a culture of said strain, a lysate of said strain, or a mixture thereof for the manufacture of a pharmaceutical preparation to aid in anti-cancer treatment.

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