Plasma TCTP as biomarker indicative of cancer treatment responsiveness

Abstract

The present invention relates to a method for diagnosing whether anticancer therapy will exhibit responsiveness in a particular patient. The anticancer therapy may include chemotherapy or cancer immunotherapy. Specifically, whether anticancer therapy will exhibit responsiveness in a particular patient can be confirmed through a TCTP level in the plasma of the corresponding patient. In such an aspect, the present invention also relates to use of plasma TCTP as a biomarker indicative of responsiveness to anticancer therapy.

Description

Plasma TCTP as a biomarker of cancer treatment responsiveness

[0001] The present invention relates to a method for diagnosing whether a cancer treatment method (chemotherapy) will be responsive to a specific patient. The chemotherapy may include chemotherapy or immunotherapy. Specifically, whether a specific patient will be responsive to the chemotherapy can be determined by measuring the plasma TCTP level of the patient. In this regard, the present invention also relates to the use of plasma TCTP as a biomarker indicating responsiveness to chemotherapy. The present invention also relates to a method for providing information regarding whether to add a second chemotherapy based on the results of diagnosing whether a cancer patient will be responsive to a primary chemotherapy. Furthermore, the present invention also relates to a method for increasing the responsiveness of a cancer treatment to a patient diagnosed as having a low responsiveness to chemotherapy due to high plasma TCTP levels by administering chemotherapy containing an anti-TCTP antibody to the patient.

[0002] While various methods have been developed to effectively treat cancer, chemotherapy using anticancer drugs has demonstrated excellent anticancer effects in clinical trials due to its ability to effectively kill cancer cells. Furthermore, chemotherapy remains the most widely used treatment because it is relatively inexpensive compared to other cancer treatments and exhibits excellent efficacy in most cancers.

[0003] However, resistance to anticancer drugs developed in cancer cells significantly reduces the effectiveness and sensitivity of chemotherapy, leading to cancer recurrence and treatment failure. Cancer cells are inherently resistant to anticancer drugs, and even those that exhibit high responsiveness to chemotherapy can develop resistance during treatment.

[0004] Recently, interest in cancer immunotherapy, which leverages the patient's own immune system, has grown, and active research and development are underway on various immunotherapy techniques and target molecules. Immunotherapy refers to any drug that prevents cancer cells from evading the body's immune system or enhances immune cells' ability to recognize and attack cancer cells. Because it works through the body's immune system, it has fewer side effects and can potentially lead to longer survival for cancer patients compared to other anticancer drugs. However, these immunotherapy drugs are not effective for all cancer patients. Therefore, predicting immunotherapy responsiveness is crucial for predicting the effectiveness of immunotherapy in cancer patients.

[0005] TCTP is a highly conserved protein in eukaryotes. It is located in both the cytoplasm and nucleus, expressed in various tissues, and regulated in response to a wide range of extracellular stimuli. TCTP is also found as a dimer and is known to interact with other proteins, including MCL1 and p53 (Acunzo, J. et al., Cancer treatment reviews 40.6 (2014): 760-769). Recently, it has been shown that TCTP is released from tumor cells, particularly damaged or dead tumor cells under stress conditions, and that inhibition of extracellular TCTP suppresses the function of suppressive immune cells in the tumor immune microenvironment, resulting in antitumor effects (Hangai, S. et al., Nature immunology 22.8 (2021): 947-957).

[0006] The inventors of the present invention sought to provide a method for effectively predicting or diagnosing responsiveness or resistance to anticancer therapy, and in particular, focused on the fact that TCTP is released from tumor cells, and explored the usefulness of TCTP as a biomarker.

[0007] Unexpectedly, the inventors of the present invention have found that the level of TCTP in plasma correlates with the responsiveness to anticancer therapy, particularly anticancer therapy involving the administration of chemotherapeutic agents or immunotherapeutic agents, particularly anti-PD-1 antibody therapeutics.

[0008] Based on this, the present invention provides a method for providing information on responsiveness to anticancer therapy by measuring the level of TCTP in the plasma of a cancer patient. The anticancer therapy may preferably include chemotherapy or immunotherapy, and in particular, the immunotherapy may involve the administration of an anti-PD-1 antibody therapeutic agent. The responsiveness may be a widely used indicator in the field of cancer treatment technology that indicates responsiveness to anticancer therapy, and may include, for example, progression-free survival or overall survival.

[0009] Furthermore, the present invention may further comprise a step of providing information regarding responsiveness to chemotherapy by measuring the level of TCTP in the plasma of a cancer patient, and providing information on whether to add a second chemotherapy based on such responsiveness information. Specifically, the present invention may provide a method for directing the use (e.g., combination) of a second chemotherapy, preferably an chemotherapy involving the administration of an immunotherapy agent, to a patient predicted to have a low responsiveness to chemotherapy based on the level of TCTP in the plasma.

[0010] Furthermore, the present invention can provide information on the responsiveness to anticancer therapy by measuring the level of TCTP in the plasma of cancer patients, and can provide a method for increasing the responsiveness to cancer therapy based on such responsiveness information. Specifically, the present invention can provide a method for directing the use (e.g., combination therapy) of anticancer therapy comprising an anti-TCTP antibody to a patient predicted to have a low responsiveness to anticancer therapy based on plasma TCTP levels.

[0011] While TCTP has been known to be a potential target for cancer therapy, the finding that TCTP levels are associated with chemotherapy response is a novel finding. Specifically, the finding that TCTP levels in peripheral blood plasma, rather than intracellular TCTP levels or levels in the tumor immune microenvironment (the extracellular environment) associated with chemotherapy response was completely unexpected. Furthermore, the finding that TCTP levels are associated with responsiveness to chemotherapy or immunotherapy (particularly anti-PD-1 therapy) was also completely unexpected.

[0012] The present invention provides a method for predicting or assessing responsiveness to chemotherapy by measuring plasma TCTP levels in cancer patients. This allows for the development of more tailored chemotherapy strategies for each patient. Furthermore, for patients predicted to have low responsiveness, complementary treatments, such as additional chemotherapy or administration of anti-TCTP antibodies, can be offered, thereby enhancing therapeutic efficacy. Furthermore, utilizing plasma TCTP levels as a biomarker can avoid unnecessary treatments and improve patient prognosis through personalized treatment. In particular, the present invention demonstrates the previously unknown utility of plasma TCTP as an indicator of chemotherapy responsiveness, thereby contributing to the development of new clinical diagnostic and treatment strategies.

[0013] Figure 1 is a flow chart of an experimental method for measuring the level of TCTP from plasma samples obtained from patients who received chemotherapy and patients who received nivolumab and analyzing the correlation with treatment response.

[0014] Figure 2 shows the results of progression-free survival and overall survival (OS) in patients receiving chemotherapy with high and low plasma TCTP levels. It should be noted that both PFS and OS were significantly higher in patients with low plasma TCTP levels than in those with high plasma TCTP levels.

[0015] Figure 3 shows the results of progression-free survival and overall survival (OS) in patients receiving nivolumab, with high and low plasma TCTP levels. It should be noted that both PFS and OS were significantly higher in patients with low plasma TCTP levels than in those with high plasma TCTP levels.

[0016] Figure 4 shows the change in tumor volume of B16F10 cells over time when treated with anti-PD-1 antibody and anti-TCTP antibody alone or in combination.

[0017] Figure 5 shows the change in tumor volume of SL4 cells over time when treated with anti-CTLA-4 antibody and anti-TCTP antibody alone or in combination.

[0018] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Generally, the terms used herein are those well known and commonly used in the art.

[0019] The embodiments described in this specification and the configurations depicted in the drawings are only one embodiment of how the present invention is realized and do not fully represent the technical idea of ​​the present invention. Therefore, it should be understood that there may be various equivalents, modifications, and applicable examples that can replace them at the time of this application. In addition, the various aspects and embodiments described in this specification can be applied to other aspects and embodiments, and all combinations of the various elements described in the present invention fall within the scope of the present invention, and the scope of the present invention cannot be considered limited by the specific description described below.

[0020] In this specification, the use of the singular includes the plural unless specifically stated otherwise. As used herein, it should be noted that the singular form includes plural referents unless the context clearly dictates otherwise. In this application, the use of "or" means "and / or" unless otherwise stated.

[0021] The term “comprising” as used herein, unless otherwise specified, is understood to be an open-ended expression that essentially includes the described components, ingredients, steps, etc., but does not exclude the presence of other components, ingredients, steps, etc. Accordingly, the term “comprising” is interpreted to include the more limited meaning of “consisting of” or “consisting essentially of.”

[0022] The expression “for” as used in this specification and claims not only means that the composition or material is designed to be used for a particular use, but also includes the meaning that it has functions or characteristics that are suitable or useful for that use even if it is not actually used for that use.

[0023] As used herein, "TCTP" (Translationally Controlled Tumor Protein) refers to a highly conserved, multifunctional protein involved in various cellular physiological processes such as cell growth, apoptosis, and immune response, and refers to a protein whose amino acid sequence is described in UniProt Accession Number P13693. In addition, TCTP in the present invention may include variants, homologs, and isoforms that are substantially identical to or homologous to the above sequence and maintain the known biological activity of TCTP. The TCTP may be present in the plasma of cancer patients, and its level may be utilized as a biomarker related to responsiveness to anticancer therapy.

[0024] As used herein, the term "plasma TCTP level" refers to the concentration or absolute amount of TCTP protein present in the plasma collected from a subject (e.g., a cancer patient) after removing blood cells, etc. from peripheral blood and separating the plasma. The method for measuring the plasma TCTP level in the present invention is not limited to a specific one, and may be performed through enzyme-linked immunosorbent assay (e.g., ELISA), immunoblot, immunoprecipitation, mass spectrometry, or other known protein quantification methods. In addition, the amount of TCTP in the plasma may be measured once or repeatedly for comparison before and after treatment of a patient, or for predicting responsiveness to anticancer therapy, and may be expressed as an absolute value or a change from baseline.

[0025] In addition, in the present invention, the plasma TCTP level can be defined not only as the total protein amount of TCTP but also as the amount of a specific isoform or variant (e.g., phosphorylated form, etc.), and in such cases, a measurement method using a specific antibody or a variant-specific analysis method can be used.

[0026] As used herein, "cancer therapy" refers to a general range of pharmacological treatments designed to inhibit the proliferation or induce the death of cancer cells, and may be administered as monotherapy or combination therapy. Examples of cancer therapies include, but are not limited to, chemotherapy, immunotherapy, targeted therapy, antibody therapy, antibody-drug conjugate therapy, cell therapy-based therapy (e.g., CAR-T cell therapy), and radiotherapy using radiopharmaceuticals. These treatment strategies may be selected and combined based on various factors, including tumor type, stage, genetic mutation, the patient's immune status, and overall health.

[0027] In this specification, “chemotherapy” refers to a treatment method using a small molecule anticancer agent that inhibits the growth, survival, or replication of cancer cells or induces apoptosis by disrupting essential biological pathways of cancer cells, such as DNA replication, cell division, and protein synthesis. The chemotherapy used in the present invention may include, but is not limited to, fluoropyrimidine drugs that inhibit DNA and RNA synthesis (e.g., 5-fluorouracil, capecitamine, tegafur, S-1, etc.) and platinum drugs that form DNA cross-links between DNA strands to interfere with DNA replication and induce apoptosis (e.g., cisplatin, carboplatin, oxaliplatin).

[0028] As used herein, "immunotherapy" refers to a treatment method that activates or modulates a patient's immune system to recognize and eliminate cancer cells. Immunotherapy is a strategy that overcomes the phenomenon of cancer cells avoiding the immune response through immune evasion mechanisms and helps the patient's immune cells effectively attack the cancer cells, and may include various approaches. Specific examples include, but are not limited to, immune checkpoint inhibitors that block the activity of immune checkpoint proteins in cancer cells or the tumor microenvironment, such as anti-PD-1 antibodies, anti-PD-L1 antibodies, and anti-CTLA-4 antibodies; chimeric antigen receptor T cell (CAR-T) therapy, which genetically modifies a patient's T cells to recognize tumor-specific antigens and then injects them into the body; cancer vaccines that induce an immune response to tumor-specific antigens; immune cell therapy that promotes an immune response; and cytokine-based therapeutics. Immunotherapy can be used alone or in combination with chemotherapy, targeted anticancer agents, antibody therapies, radiation therapy, and other treatments to achieve synergistic effects. The immunotherapy described herein may include any one or a combination of the various treatment strategies described above.

[0029] As used herein, the term “antibody” refers to an immunoglobulin protein that can specifically bind to an antigen, and a molecule that has the function of recognizing and binding to a specific antigen (epitope) in vivo or in vitro. Antibodies generally recognize a specific epitope of an antigen through an antibody variable region. In addition to the typical Y-shaped full-length antibody, the shape and structure of antibodies can be provided in various forms, such as antibody fragments containing an antigen-binding site, such as Fab, F(ab')2, scFv, or nanobodies, and the term “antibody” as used herein includes all of these forms. In addition, the antibody referred to herein may include a human antibody, a humanized antibody, a chimeric antibody, or a derivative thereof, and may be a form in which pharmacokinetic properties (e.g., half-life), efficacy, stability, or tissue penetration are improved through modification of the Fc region, regulation of the glycosylation pattern, Fc engineering, etc. These antibodies may be used alone or in combination with other anticancer therapies (e.g., chemotherapy, targeted therapy, immunotherapy, etc.).

[0030] As used herein, the term “PD-1 antibody” refers to an antibody that specifically binds to the PD-1 (programmed cell death protein 1) protein, thereby blocking the binding between PD-1 and its ligand PD-L1 or PD-L2, thereby restoring T cell activation and promoting an anticancer immune response. PD-1 is an immune checkpoint receptor expressed on the surface of immune cells, particularly activated T cells, and is a protein involved in cancer cells suppressing the immune response through an immune evasion mechanism. The PD-1 antibody referred to herein may include a human, humanized, or chimeric antibody, and may include a full-length antibody, antibody fragment, or a variant thereof. Examples of PD-1 antibodies include nivolumab, pembrolizumab, etc., but the PD-1 antibody referred to in the present invention is not limited thereto.

[0031] The term “PD-L1 antibody” as used herein refers to an antibody that specifically binds to the PD-L1 (programmed death-ligand 1) protein, thereby restoring T cell activation and promoting an anticancer immune response by blocking or inhibiting the interaction between PD-L1 and its receptor PD-1. PD-L1 is expressed on various tumor cells and immunosuppressive cells in the tumor microenvironment, and plays a role in suppressing the immune response of T cells and inducing immune evasion of cancer cells. The PD-L1 antibody referred to in the present invention includes a human, humanized, or chimeric antibody, and may include a full-length antibody, an antibody fragment, or a derivative or variant thereof. Specific examples of the PD-L1 antibody include atezolizumab, durvalumab, avelumab, etc., but the PD-L1 antibody referred to in the present invention is not limited to these.

[0032] The term “CTLA-4 antibody” as used herein refers to an antibody that specifically binds to the CTLA-4 (Cytotoxic T-Lymphocyte Antigen-4) protein, thereby blocking or inhibiting the pathway by which CTLA-4 inhibits T cell activation, thereby promoting T cell immune responses and enhancing anticancer immune responses. CTLA-4 is mainly expressed in activated T cells and regulatory T cells (Treg), and plays a role in suppressing excessive T cell activation and regulating the balance of immune responses. The CTLA-4 antibody referred to in the present invention includes a human, humanized, or chimeric antibody, and may include a full-length antibody, an antibody fragment, or a variant or derivative thereof. Specific examples of the CTLA-4 antibody include ipilimumab and tremelimumab, but the CTLA-4 antibody referred to in the present invention is not limited thereto.

[0033] In this specification, “nivolumab” refers to a drug that is a human monoclonal antibody that specifically binds to PD-1, and restores the immune function of T cells and promotes anticancer immune response by blocking the binding between PD-1 and its ligand, PD-L1 or PD-L2. Nivolumab is commercially available under the product name Opdivo®. Nivolumab as referred to in the present invention is interpreted to include not only the original manufacturer’s product, but also biosimilars, variants, or pharmaceutically acceptable formulations having the same or substantially the same sequence and function.

[0034] As used herein, “combination” means administering or applying two or more therapeutic agents, for example, two or more drugs, treatments, or treatment methods, simultaneously or in a specific sequence. Combination includes not only concurrent administration, i.e., administering two or more treatments at the same time, but also sequential administration, i.e., administering each treatment agent step-by-step at a specific time interval or in a specific sequence. Furthermore, combination as used herein includes not only cases where two or more treatments are combined and administered in a single formulation, but also cases where they are administered in different formulations, routes, or schedules, and encompasses all ways in which each treatment agent exerts its therapeutic effect independently or complementarily.

[0035] In this specification, “cancer” refers to a malignant neoplasm formed when normal cells in the body abnormally proliferate through genetic or epigenetic changes, and their regulatory functions, such as cell cycle control, apoptosis, and growth signal transmission, are damaged. Cancer cells have characteristics such as abnormal proliferation, invasion of surrounding tissues, possibility of distant metastasis, drug resistance, and immune evasion, and thus can interfere with the function of normal tissues or cause systemic health deterioration. Depending on the site of occurrence and cell of origin, cancer is classified into solid cancer (e.g., lung cancer, breast cancer, stomach cancer, colon cancer, etc.) and blood cancer (e.g., leukemia, lymphoma, multiple myeloma, etc.), and each cancer type may differ in pathological characteristics, genetic mutations, disease progression patterns, and treatment responses. The cancer referred to in this specification is not limited to the above classification, and is a concept that includes all forms of malignant tumors, i.e., solid cancers and blood cancers, and may include not only clinically diagnosable cancers but also precancerous lesions, precancerous cellular changes, or early-stage cancers.

[0036] In this specification, “solid cancer” refers to a cancer that forms a mass (lump) in a tissue or organ, and refers to a neoplastic disease that is distinct from hematological cancer, which mainly grows in body fluids such as blood or bone marrow. Solid cancers generally originate from cells such as epithelial cells, connective tissue, nerve tissue, and muscle tissue, and have various forms and characteristics depending on the type and location of the tissue where the tumor develops. Examples of solid cancers include lung cancer, breast cancer, colon cancer, stomach cancer, esophageal cancer, liver cancer, pancreatic cancer, kidney cancer, bladder cancer, prostate cancer, ovarian cancer, cervical cancer, endometrial cancer, skin cancer (melanoma, etc.), head and neck cancer, brain tumor, osteosarcoma, soft tissue sarcoma, etc. All of these form solid tumor tissue, and the disease progresses mainly in the form of structural deformation of the relevant tissue, tumor growth, metastasis, etc. The solid cancer referred to in this specification is not limited to the above examples, and may include all carcinomas that develop in a specific tissue or organ in the body and form a solid tumor mass.

[0037] In this specification, “responsiveness” refers to the clinical or therapeutic benefit that a cancer patient can obtain through a specific anticancer therapy, which can be evaluated based on objective response rate (ORR), progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR), or other indicators related to tumor progression or survival. Evaluation of responsiveness can generally be performed through a comprehensive analysis of various indicators such as changes in tumor size, disease progression, survival rate, and quality of life (QoL), and may vary depending on the patient’s treatment history, cancer type and stage, and molecular biological characteristics.

[0038] The term “poorly responsive” in this specification means that a cancer patient does not show a clinically significant therapeutic effect to a specific anticancer therapy, or the response is limited or temporary, including, for example, no inhibition of cancer progression, no significant reduction in tumor size, or no statistically significant improvement in progression-free survival or overall survival.

[0039] The above-mentioned responsiveness assessment can be performed according to RECIST (Registered Evaluation of Cancer Therapy Response), iRECIST, or separate criteria for assessing immunotherapy response. If necessary, imaging, biomarker analysis, or patient subjective reports can be used in conjunction to further refine the assessment. Therefore, the concept of responsiveness in this specification is not limited to a single indicator, but can be interpreted and applied in various ways depending on the individual patient's clinical situation and assessment criteria.

[0040] In the present invention, the reference plasma TCTP level for determining "high or low TCTP levels" may be set based on the plasma TCTP concentration that can represent a cancer patient or patient group (or a patient group with relatively high responsiveness) showing response to the corresponding anticancer therapy. Here, the "patient group showing response" refers to a patient or patient group in whom a clinically significant therapeutic effect has been confirmed, and may be defined, for example, as a case in which the progression-free survival (PFS) or overall survival (OS) is above the reference value.

[0041] The reference plasma TCTP level in the present invention refers to a value that can statistically significantly distinguish between a patient group with a high responsiveness to a specific anticancer therapy and a patient group with a low responsiveness, and can be determined through clinical trials, prospective or retrospective observational studies, or patient group analysis. The setting of such a reference value can be appropriately determined by a person skilled in the art according to general experimental and statistical methods in the relevant field, and can be adjusted according to various clinical and biological factors such as the type of cancer to be applied, the type of anticancer therapy (e.g., chemotherapy, immunotherapy, targeted therapy, etc.), the patient's age, sex, race, general condition, and genotype.

[0042] The reference plasma TCTP level in the present invention may also be set based on the TCTP concentration in the plasma of a normal person (non-cancer patient). In this case, the reference plasma TCTP level may be determined based on the average TCTP concentration in a normal person, the upper limit of the normal range, or a statistical indicator (e.g., mean, median, quartile, standard deviation, etc.) of the TCTP concentration measured in a normal population. For example, a case in which a level is statistically significantly higher than the TCTP concentration in the plasma of a normal person can be determined as having a “high TCTP level,” and this can be used as a criterion for evaluating the correlation with anticancer therapy response.

[0043] For example, reference plasma TCTP levels can be set at various concentration ranges, such as 1 ng / mL to 1 mg / mL, 1 ng / mL to 100 μg / mL, 1 ng / mL to 10 μg / mL, 1 ng / mL to 1 μg / mL, 10 ng / mL to 1 mg / mL, 10 ng / mL to 100 μg / mL, 10 ng / mL to 10 μg / mL, 10 ng / mL to 1 μg / mL, 100 ng / mL to 1 mg / mL, 100 ng / mL to 100 μg / mL, 100 ng / mL to 10 μg / mL, 100 ng / mL to 1 μg / mL, 100 ng / mL to 500 ng / mL, 200 ng / mL to 500 ng / mL, etc., based on plasma samples. The concentration range may vary depending on the specific measurement method (e.g., ELISA, immunoblot, mass spectrometry, etc.) and may be adjusted according to the sensitivity and specificity of the analysis method.

[0044] Meanwhile, a patient or patient group showing responsiveness (or a patient group with relatively high responsiveness) may be set as, for example, a patient whose progression-free survival period for the corresponding anticancer therapy is 1 month or more, 2 months or more, 3 months or more, 4 months or more, 6 months or more, 8 months or more, 10 months or more, 12 months or more, 24 months or more, 36 months or more, 48 months or more, 60 months or more, or 72 months or more, and / or an overall survival period for the corresponding anticancer therapy is 1 month or more, 2 months or more, 3 months or more, 4 months or more, 6 months or more, 8 months or more, 10 months or more, 12 months or more, 24 months or more, 36 months or more, 48 months or more, 60 months or more, 72 months or more, 84 months or more, or 96 months or more, and / or a patient whose objective response rate of the tumor is statistically significantly improved after administration of the corresponding anticancer therapy.

[0045] Furthermore, patients or patient groups showing a response (or patients with a relatively high response) may be those for whom responsiveness is maintained or tumor progression is suppressed under the same chemotherapy regimen without the introduction of additional chemotherapy or combination therapy. In other words, these patients may achieve sufficient clinical benefit (e.g., tumor size reduction, symptom improvement, prolonged survival, etc.) with monotherapy alone.

[0046] In this specification, "progression-free survival (PFS)" refers to the period from the start of treatment until disease progression or death of the patient. Disease progression is assessed by factors such as an increase in tumor size, the appearance of new lesions, or clinically significant deterioration, and can generally be determined according to known evaluation criteria such as RECIST (Response Evaluation Criteria for Oncology Therapy) or iRECIST.

[0047] In this specification, "Overall Survival (OS)" refers to the period from the initiation of treatment or diagnosis to the patient's death. It is an objective and absolute clinical indicator indicating a patient's prolongation of survival. OS is measured inclusively of death from all causes and can be confirmed through periodic follow-up observations during clinical trials or patient monitoring.

[0048] As used herein, the term "method of providing information" refers to a set of methods for generating or presenting information useful for clinical or medical decision-making, such as diagnosing a disease, predicting prognosis, predicting treatment response, or determining treatment strategies, through procedures such as measuring, analyzing, and interpreting specific biological markers. These methods may include procedures that provide clinicians, healthcare providers, or patients with data, guidelines, or criteria for decision-making, even if they do not directly demonstrate a treatment effect on a disease or involve direct treatment of the patient.

[0049] For example, the “method for providing information” referred to in the present invention may include a step of measuring TCTP levels in the plasma of a cancer patient, comparing the levels with a baseline or reference value, or generating information predicting or evaluating responsiveness to anticancer therapy through comparative analysis with existing patient population data, and delivering the information to medical staff, patients, or other users. Such information may contribute to clinical decision-making regarding selection of treatment methods for patients, adjustment of treatment intensity, and determination of the necessity of combination therapy. In addition, the method for providing information may present analysis results in the form of numbers, grades, categories, or reports, and in some cases, may include software, algorithms, or database-based interpretation and prediction systems.

[0050] One aspect of the present invention provides the use of TCTP in plasma to provide information regarding the responsiveness of a cancer patient to anticancer therapy.

[0051] The inventors of the present invention analyzed the correlation between the treatment response of patients administered chemotherapy or immunotherapy and the level of TCTP from plasma samples, and confirmed that there was a significant correlation between the level of TCTP in plasma and treatment response, thereby finding that the level of TCTP in the plasma of cancer patients can provide information necessary for predicting the response to anticancer therapy such as chemotherapy or immunotherapy for cancer treatment.

[0052] In some embodiments, the cancer patient is a solid cancer patient. In some embodiments, the solid cancer is gastric cancer.

[0053] In some embodiments, the anticancer therapy comprises chemotherapy. In some embodiments, the anticancer therapy involves administration of a fluoropyrimidine, platinum, or both.

[0054] In some embodiments, the anticancer therapy comprises immunotherapy. In some embodiments, the immunotherapy involves administration of an anti-PD-1 antibody. In some embodiments, the immunotherapy involves administration of the nivolumab antibody.

[0055] In some embodiments, the responsiveness is determined by progression-free survival and / or overall survival.

[0056] One aspect of the present invention provides a method for providing information on the responsiveness of a cancer patient to anticancer therapy, comprising the steps of (a) measuring the level of TCTP in plasma isolated from a cancer patient, and (b) providing information necessary for predicting the responsiveness to anticancer therapy based on the measured plasma TCTP level.

[0057] In the above step (a), the “step of measuring the level of TCTP in plasma isolated from a cancer patient” is a step that can be easily performed by a person skilled in the art through known technical means, and specifically includes a procedure of collecting a blood sample from a cancer patient, separating plasma from the blood, and then quantifying the concentration or absolute amount of TCTP protein present in the plasma. The quantification of TCTP in the plasma can be performed using a conventional biochemical or immunological analysis method such as an enzyme-linked immunosorbent assay (ELISA), an immunoblot (western blot), an immunoprecipitation method, or a mass spectrometry method.

[0058] In addition, the antibody used for measuring the TCTP level in the present invention is an antibody that can specifically bind to TCTP, and may be provided in the form of a monoclonal antibody, a polyclonal antibody, or an antibody fragment. The measured concentration of TCTP can be converted into an absolute concentration based on a standard curve, and can be expressed in various units such as mg / mL, μg / mL, and ng / mL.

[0059] A higher measured plasma TCTP level than the reference plasma TCTP level indicates that the cancer patient is less responsive to chemotherapy.

[0060] In some embodiments, the cancer patient is a solid cancer patient. In some embodiments, the solid cancer is gastric cancer.

[0061] In some embodiments, the anticancer therapy comprises chemotherapy. In some embodiments, the anticancer therapy involves administration of a fluoropyrimidine, platinum, or both.

[0062] In some embodiments, the anticancer therapy comprises immunotherapy. In some embodiments, the immunotherapy involves administration of an anti-PD-1 antibody. In some embodiments, the immunotherapy involves administration of the nivolumab antibody.

[0063] In some embodiments, the responsiveness is determined by progression-free survival and / or overall survival.

[0064] In some embodiments, a method for providing information about responsiveness to anticancer therapy in a cancer patient, comprising the steps of (a) measuring the level of TCTP in plasma isolated from the cancer patient, and (b) providing information necessary for predicting responsiveness to anticancer therapy based on the measured plasma TCTP level, may further comprise the step of (c) providing information about whether to use a second anticancer therapy for the patient.

[0065] In some embodiments, the second anticancer therapy involves administration of an immunotherapy agent.

[0066] In some embodiments, the second anticancer therapy involves administration of an antibody selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA4 antibody.

[0067] In some embodiments, the second anticancer therapy involves administration of an anti-TCTP.

[0068] In some embodiments, the anti-TCTP antibody is administered alone or in combination with an immunotherapy agent.

[0069] In some embodiments, the anti-TCTP antibody is used in combination with an antibody selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA4 antibody.

[0070] One aspect of the present invention relates to the use of anti-TCTP antibodies to increase the responsiveness of cancer patients to cancer treatment.

[0071] The inventors of the present invention analyzed the correlation between treatment response and plasma TCTP levels in patients receiving chemotherapy or immunotherapy. They confirmed that higher TCTP levels tended to be associated with lower treatment response. Accordingly, they demonstrated that lowering plasma TCTP levels using anti-TCTP antibodies could increase responsiveness to chemotherapy or immunotherapy.

[0072] Furthermore, experiments have shown that combined use of anti-TCTP antibodies with immunotherapies, such as anti-PD-1 antibodies and anti-CTLA-4 antibodies, significantly improves antitumor efficacy. This suggests that combined administration of anti-TCTP antibodies may enhance responsiveness to immunotherapies.

[0073] In some embodiments, the cancer patient is a solid cancer patient. In some embodiments, the solid cancer is gastric cancer.

[0074] In some embodiments, the cancer treatment comprises chemotherapy. In some embodiments, the cancer treatment involves administration of a fluoropyrimidine, a platinum, or both.

[0075] In some embodiments, the cancer treatment comprises immunotherapy. In some embodiments, the immunotherapy involves administration of an anti-PD-1 antibody. In some embodiments, the immunotherapy involves administration of the nivolumab antibody.

[0076] In some embodiments, the increased responsiveness means an increase in progression-free survival and / or overall survival.

[0077] One aspect of the present invention provides a method for increasing the responsiveness of a cancer patient to cancer treatment, comprising the steps of: (a) measuring the level of TCTP in plasma isolated from a cancer patient; (b) providing information necessary for predicting responsiveness to anticancer therapy based on the measured plasma TCTP level; and (c) administering an anticancer therapy comprising an anti-TCTP antibody to a cancer patient having a high plasma TCTP level.

[0078] In the above step (a), the “step of measuring the level of TCTP in plasma isolated from a cancer patient” is a step that can be easily performed by a person skilled in the art through known technical means, and specifically includes a procedure of collecting a blood sample from a cancer patient, separating plasma from the blood, and then quantifying the concentration or absolute amount of TCTP protein present in the plasma. The quantification of TCTP in the plasma can be performed using a conventional biochemical or immunological analysis method such as an enzyme-linked immunosorbent assay (ELISA), an immunoblot (western blot), an immunoprecipitation method, or a mass spectrometry method.

[0079] In addition, the antibody used for measuring the TCTP level in the present invention is an antibody that can specifically bind to TCTP, and may be provided in the form of a monoclonal antibody, a polyclonal antibody, or an antibody fragment. The measured concentration of TCTP can be converted into an absolute concentration based on a standard curve, and can be expressed in various units such as mg / mL, μg / mL, and ng / mL.

[0080] A higher measured plasma TCTP level than the reference plasma TCTP level indicates that the cancer patient is less responsive to chemotherapy.

[0081] In some embodiments, the cancer patient is a solid cancer patient. In some embodiments, the solid cancer is gastric cancer.

[0082] In some embodiments, the anticancer therapy comprises chemotherapy. In some embodiments, the anticancer therapy involves administration of a fluoropyrimidine, platinum, or both.

[0083] In some embodiments, the anticancer therapy comprises immunotherapy. In some embodiments, the immunotherapy involves administration of an anti-PD-1 antibody. In some embodiments, the immunotherapy involves administration of the nivolumab antibody.

[0084] In some embodiments, the responsiveness is determined by progression-free survival and / or overall survival.

[0085] In some embodiments, the anticancer therapy administered in step (c) may include an anti-TCTP antibody.

[0086] In some embodiments, the anti-TCTP antibody is administered alone or in combination with an immunotherapy agent.

[0087] In some embodiments, the anti-TCTP antibody is used in combination with an antibody selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA4 antibody.

[0088] One aspect of the present invention provides a pharmaceutical composition for increasing the responsiveness of a cancer patient to cancer treatment, comprising an anti-TCTP antibody.

[0089] In some embodiments, the cancer patient is a patient who has previously received a chemotherapy agent or an immunotherapy agent.

[0090] In some embodiments, the cancer patient is a patient who has previously received chemotherapy, wherein the chemotherapy involves administration of a fluoropyrimidine, a platinum, or both.

[0091] In some embodiments, the cancer patient is a patient who has previously received an immunotherapy agent, wherein the immunotherapy agent is an anti-PD-1 antibody. In some embodiments, the anti-PD-1 antibody is nivolumab.

[0092] In some embodiments, the cancer patient has plasma TCTP levels higher than those of a normal person.

[0093] In some embodiments, the cancer patient is a patient whose plasma TCTP level is measured to be higher than a reference plasma TCTP level. The reference plasma TCTP level is as described herein in connection with methods for providing information regarding responsiveness to anticancer therapy.

[0094] In some embodiments, the pharmaceutical composition comprises, in addition to the anti-TCTP antibody, chemotherapy. The chemotherapy may involve, but is not necessarily limited to, administration of a fluoropyrimidine, a platinum, or both.

[0095] In some embodiments, the anti-TCTP antibody and chemotherapy are administered in combination, i.e., administered simultaneously or sequentially.

[0096] In some embodiments, the pharmaceutical composition comprises an anti-TCTP antibody, along with an immunotherapy. The immunotherapy may be selected from, but is not necessarily limited to, an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA4 antibody.

[0097] In some embodiments, the immunotherapy involves administration of nivolumab.

[0098] In some embodiments, the anti-TCTP antibody and immunotherapy are used in combination, i.e., administered simultaneously or sequentially.

[0099] In some embodiments, the cancer patient is a solid cancer patient. In some embodiments, the solid cancer is gastric cancer.

[0100] In some embodiments, the pharmaceutical composition is intended for administration to a patient who has previously received anticancer therapy involving administration of a chemotherapy agent or an immunotherapy agent, wherein the patient exhibits improved responsiveness compared to the previously administered anticancer therapy.

[0101] In some embodiments, the improved responsiveness is improved progression-free survival and / or overall survival.

[0102] The pharmaceutical composition of the present invention comprises an anti-TCTP antibody as an active ingredient and may additionally comprise a chemotherapeutic agent or an immunotherapy agent.

[0103] In some embodiments, the chemotherapy may involve, but is not necessarily limited to, administration of a fluoropyrimidine or a platinum, or both.

[0104] In some embodiments, the immunotherapy may be selected from, but is not necessarily limited to, the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA4 antibody. In some embodiments, the immunotherapy is nivolumab.

[0105] In addition to the above-mentioned active ingredient, the above-mentioned pharmaceutical composition may be formulated with pharmaceutically acceptable carriers, excipients, stabilizers, preservatives, solubilizers, viscosity-adjusting agents, adhesives, or other additives. These compositions may be prepared in various forms depending on the purpose of administration, route of administration, and the conditions of the patient to be treated.

[0106] In addition to the above-described active ingredient, the pharmaceutical composition of the present invention may include one or more pharmaceutically acceptable excipients. The excipients are components used to improve the stability, physical properties, ease of processing, and bioavailability of the composition, and include substances widely used in the field of conventional pharmaceuticals. Exemplary excipients that can be used include fillers, binders, lubricants, disintegrants, coating agents, wetting agents, solvents, isotonic agents, buffers, stabilizers, and preservatives. The type, mixing ratio, addition order, etc. of such excipients may vary depending on the formulation of the composition, the properties of the active ingredient, the application site, and the administration route, and these are well known to those skilled in the art and can be appropriately selected. For specific formulation design and excipient selection not described herein, reference may be made to pharmaceutical literature such as Remington: The Science and Practice of Pharmacy, 22nd ed., Pharmaceutical Press (2012) or Martindale: The Complete Drug Reference, 38th ed., Pharmaceutical Press (2014).

[0107] The pharmaceutical composition of the present invention may be provided in a formulation for systemic administration, including injectable solutions, intravenous injections, subcutaneous injections, intramuscular injections, tablets, capsules, or liposome / nanoparticle-based delivery systems. Systemic formulations can be used when simultaneous action is required on multiple lesions or when topical application is limited. The pharmaceutical composition of the present invention can be manufactured in various ways according to pharmaceutical technology, taking into account the stability, dissolution rate, tissue permeability, and biocompatibility of the active ingredient.

[0108] The pharmaceutical composition of the present invention can be administered via various routes of administration, enabling drug delivery into the body for the treatment of cancer. The composition can be administered systemically or locally, and for example, intravenous injection, intramuscular injection, subcutaneous injection, topical injection, oral topical application, and other routes (oral, nasal, transdermal) can also be considered depending on the pharmaceutical design.

[0109] The pharmaceutical composition of the present invention can be administered once or repeatedly, and the dosage, administration interval, and administration period can be adjusted at the discretion of a medical professional depending on the patient's condition (age, weight, degree of disease progression, etc.), characteristics of the active ingredient, and formulation.

[0110] The dosage and schedule of administration may be optimized based on animal test results, clinical data, and the judgment of a skilled practitioner.

[0111] The pharmaceutical composition of the present invention comprises a therapeutically effective amount of an anti-TCTP antibody. The term "therapeutically effective amount" refers to an amount sufficient to increase a cancer patient's responsiveness to chemotherapy, inhibit cancer progression, reduce tumor size, or prolong the patient's survival. The therapeutically effective amount may vary depending on the patient's age, sex, weight, type and severity of the disease, the patient's general health, other concomitant treatments, the route and frequency of administration, and other factors, and can be determined by a skilled practitioner based on appropriate clinical judgment.

[0112] The present invention may be as follows based on the above-described contents, but is not limited thereto.

[0113] 1. A method for providing information on the responsiveness of a cancer patient to anticancer therapy, comprising: (a) measuring the level of TCTP in plasma isolated from a cancer patient; and (b) providing information necessary for predicting the responsiveness to anticancer therapy based on the measured plasma TCTP level.

[0114] 2. A method according to the above-mentioned first paragraph, wherein the plasma TCTP level measured in step (a) is higher than the reference plasma TCTP level, indicating that the cancer patient has a low response to anticancer therapy.

[0115] 3. A method according to any one of the above-mentioned clauses 1 and 2, wherein the anticancer treatment comprises chemotherapy.

[0116] 4. A method according to any one of the above-mentioned clauses 1 to 3, wherein the chemotherapy involves administration of a fluoropyrimidine or platinum, or both.

[0117] 5. A method according to any one of the above-mentioned clauses 1 to 4, wherein the anticancer therapy comprises immunotherapy.

[0118] 6. A method according to any one of the above-mentioned clauses 1 to 5, wherein the immunotherapy involves administration of an anti-PD-1 antibody.

[0119] 7. A method according to the above-mentioned clause 6, wherein the immunotherapy involves administration of a nivolumab antibody.

[0120] 8. A method according to any one of the above-mentioned clauses 1 to 7, wherein the responsiveness is determined by progression-free survival and / or overall survival.

[0121] 9. A method according to any one of the above-mentioned clauses 1 to 8, further comprising the step of (c) providing information on whether to use a second anticancer therapy for the patient.

[0122] 10. A method according to the above-mentioned 9th paragraph, wherein the second anticancer therapy involves administration of an immunotherapy agent.

[0123] 11. A method according to claim 9, wherein the second anticancer therapy involves administration of an antibody selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA4 antibody.

[0124] 12. A method according to the above-mentioned 9th paragraph, wherein the second anticancer therapy involves administration of an anti-TCTP antibody.

[0125] 13. A method according to claim 12, wherein the anti-TCTP antibody is used in combination with an immunotherapy agent.

[0126] 14. The method of claim 13 mentioned above, wherein the immunotherapy agent is an antibody selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA4 antibody.

[0127] 15. A method for increasing the responsiveness of a cancer patient to cancer treatment, comprising: (a) measuring the level of TCTP in plasma isolated from a cancer patient; (b) providing information necessary for predicting responsiveness to anticancer therapy based on the measured plasma TCTP level; and (c) administering an anticancer therapy comprising an anti-TCTP antibody to a cancer patient having a high plasma TCTP level.

[0128] 16. A method according to claim 15, wherein the plasma TCTP level measured in step (a) is higher than the reference plasma TCTP level, indicating that the cancer patient has a low response to anticancer therapy.

[0129] 17. A method according to any one of the above-mentioned clauses 15 and 16, wherein the anticancer treatment comprises chemotherapy.

[0130] 18. A method according to the above-mentioned clause 17, wherein the chemotherapy involves administration of a fluoropyrimidine or platinum, or both.

[0131] 19. A method according to any one of the above-mentioned clauses 15 to 18, wherein the anticancer therapy comprises immunotherapy.

[0132] 20. A method according to claim 19, wherein the immunotherapy involves administration of an anti-PD-1 antibody.

[0133] 21. A method according to claim 20, wherein the immunotherapy involves administration of a nivolumab antibody.

[0134] 22. A method according to any one of the above-mentioned clauses 15 to 21, wherein the responsiveness is determined by progression-free survival and / or overall survival.

[0135] 23. A pharmaceutical composition for increasing the responsiveness of a cancer patient to cancer treatment, comprising an anti-TCTP antibody.

[0136] 24. A pharmaceutical composition according to the above-mentioned clause 23, wherein the cancer patient is a patient who has previously been administered a chemotherapy agent or an immunotherapy agent.

[0137] 25. A pharmaceutical composition according to the above-mentioned clause 24, wherein the cancer patient shows low responsiveness to a chemotherapy agent or an immunotherapy agent.

[0138] 26. A pharmaceutical composition according to any one of the above-mentioned items 23 to 25, wherein the cancer patient has a plasma TCTP level higher than that of a normal person.

[0139] 27. A pharmaceutical composition according to any one of claims 23 to 26 mentioned above, wherein the anti-TCTP antibody is used in combination with chemotherapy.

[0140] 28. A pharmaceutical composition according to the above-mentioned item 27, wherein the chemotherapy involves administration of a fluoropyrimidine or platinum, or both.

[0141] 29. A pharmaceutical composition according to any one of claims 23 to 26 mentioned above, wherein the anti-TCTP antibody is used in combination with immunotherapy.

[0142] 30. A pharmaceutical composition according to the above-mentioned item 29, wherein the immunotherapy is selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA4 antibody.

[0143] 31. A pharmaceutical composition according to claim 30, wherein the immunotherapy is an anti-PD-1 antibody.

[0144] 32. A pharmaceutical composition according to claim 30, wherein the immunotherapy is nivolumab.

[0145] Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are provided only to illustrate the present invention and the present invention is not limited thereto.

[0146]

[0147] Example 1: Analysis of anticancer therapy response according to plasma TCTP levels.

[0148] patient population

[0149] Cohort 1 included 143 patients with metastatic gastric cancer (recurrent or locally advanced, unresectable type) who received chemotherapy containing a fluoropyrimidine and a platinum compound as first-line treatment between August 2021 and November 2023, and Cohort 2 included 167 patients with the same disease who received nivolumab as third-line (or later) treatment between August 2021 and September 2023.

[0150] Plasma TCTP ELISA kit test method

[0151] This example describes an enzyme-linked immunosorbent assay (ELISA) method for detecting TCTP protein in patient plasma. Experiments were performed using a commercially available ELISA kit (LS Bio). The materials and methods used in each experiment were according to the manufacturer's instructions, which are briefly described as follows. A monoclonal antibody specific for purified human TCTP protein was diluted to a concentration of 5 μg / mL in sodium bicarbonate buffer (pH 9.6) and incubated overnight in a microplate. To block nonspecific binding sites, 5% fetal bovine serum albumin or whole milk powder was diluted in phosphate-buffered saline (PBS) containing 0.05% TWEEN-20. The blocking solution was removed, and plasma derived from the patient was serially diluted and added to each well. After three washes, a biotinylated TCTP-specific monoclonal antibody was added and incubated. After washing each well three times, HRP (Horseradish Peroxidase)-conjugated streptavidin was added and reacted. After washing the wells, the enzyme reaction of HRP was induced using TMB (3,3',5,5'-tetramethylbenzidine) substrate. After confirming appropriate color development, the enzyme-substrate reaction was stopped by adding 2 M sulfuric acid solution. The enzyme-substrate reaction was measured by optical density at 450 nm using a microplate reader. The TCTP protein concentration in the sample was determined by comparing it to a standard curve generated using a known concentration of purified TCTP protein. The OD values ​​were plotted against a TCTP protein standard of known concentration to generate a standard curve, and the equation of the curve was derived through linear regression analysis. The derived equation was used to calculate the TCTP protein concentration in the patient samples. The results are expressed in ng / mL.

[0152] Statistical analysis method

[0153] This analysis method relates to statistical methods for analyzing the significance between plasma TCTP protein concentrations and prognostic prediction. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. PFS was defined as the time from the start of chemotherapy to the date of disease progression or death according to RECIST version 1.1 criteria, whichever occurred first. OS was defined as the time until death from any cause. Comparisons of survival outcomes between subgroups were performed using the log-rank test. The chi-square test or Fisher's exact test was used to compare categorical variables, and the maximum chi-square test was used to determine the optimal cutoff value for TCTP levels that best differentiated PFS outcomes. The cutoff value of 249.2 ng / mL was used to divide patients into high and low serum TCTP groups. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). For all statistical analyses, a two-sided P value <0.05 was considered statistically significant.

[0154] Chemotherapy response correlation analysis

[0155] Between August 2021 and November 2023, 143 patients with metastatic gastric cancer (recurrent or locally advanced, unresectable type) who received chemotherapy containing a fluoropyrimidine and a platinum compound as first-line treatment were tested for TCTP protein levels in plasma. Progression-free survival (PFS) and overall survival (OS) in the chemotherapy group were categorized into TCTP-high and TCTP-low groups based on TCTP protein concentrations derived from the statistical method described above. PFS and OS were defined according to the above-described method and estimated using the Kaplan-Meier method. Statistical significance between subgroups was assessed using the Log-rank test.

[0156] As shown in Fig. 2, analysis of the correlation between plasma TCTP levels and chemotherapy response from cohort 1 revealed that, compared to the TCPT low trial group, the TCTP high trial group showed significantly worse progression-free survival (PFS) (median PFS 3.2 months (TCTP high) vs 6.5 months (TCTP low); P=0.009) and significantly lower overall survival (OS) (median OS 8.8 months (TCTP high) vs 14.9 months (TCTP low); P=0.004).

[0157] Nivolumab Response Correlation Analysis

[0158] TCTP protein levels were detected in plasma from 167 patients with metastatic gastric cancer (recurrent or locally advanced unresectable type) who received nivolumab as third-line (or later) treatment between August 2021 and September 2023. Progression-free survival (PFS) and overall survival (OS) in the nivolumab-treated group were classified into TCTP-high and TCTP-low groups based on TCTP protein concentrations derived from the statistical method described above. PFS and OS were defined according to the above-described method and estimated using the Kaplan-Meier method. Statistical significance between subgroups was evaluated using the Log-rank test.

[0159] As shown in Figure 3, the analysis of the correlation between plasma TCTP levels and chemotherapy response from cohort 1 showed that, compared to the TCPT low trial group, the TCTP high trial group showed significantly worse progression-free survival (PFS) and significantly lower overall survival (OS).

[0160]

[0161] Example 2: Tumor proliferation inhibition effect according to single or combined administration of TCTP antibody

[0162] B16F10 (1 x 105) cells were subcutaneously inoculated into C57BL / 6 mice. Anti-TCTP antibody Ab8 (100 μg, intraperitoneally) and anti-PD-1 antibody (BioXCell; 100 μg, intravenously) were administered alone or in combination on days 1, 4, 8, 11, 15, 18, and 22 from the day of inoculation (Day 1). As a result, both anti-TCTP antibody and anti-PD-1 antibody reduced tumor size, and in particular, it was confirmed that tumor size was further reduced when anti-TCTP antibody was additionally administered to anti-PD-1 antibody compared to when anti-PD-1 antibody alone was administered (Fig. 4).

[0163] These effects were also confirmed in an experiment using SL4 cells. SL4 cells (2 x 105) were subcutaneously inoculated into C57BL / 6 mice. Anti-TCTP antibody Ab8 (100 μg, intraperitoneal administration) and anti-CTLA-4 antibody (BioXCell; 100 μg, intravenous injection) were administered alone or in combination on days 1, 4, 8, 11, 15, 18, and 22 from the day of inoculation (Day 1). As a result, both anti-TCTP antibody and anti-CTLA4 antibody reduced tumor size, and in particular, it was confirmed that when anti-TCTP antibody was additionally administered to anti-CTLA-4 antibody, tumor size was further reduced compared to when anti-CTLA-4 antibody alone was administered (Fig. 5).

[0164] The Ab8 antibody used above is an antibody having the following heavy and light chain variable region sequences.

[0165] Heavy chain variable region:

[0166] MDWTWRILFLVAAATGAHSQVQLVQSGAEVKKPGASVKVSCKASGYTFFSYAMHWVRQAPGQRLEWMGWINAGNGNTKYSQKFQDRVTITRDTSATTAYMELSSLRSEDTAVYYCASWVFDYWGQGTPVTVSS

[0167] Light chain variable region:

[0168] MRLLAQLLGLLMLWVPGSSGDIVMTQTPLSSLVTLGQPASISCRSSQSLVHRDGNTYLSWLQQRPGQPPRLLIYKISNRFFGVPDRFSGSGAGTDFTLKISRVEAEDVGVYYCMQATQFPHTFGQGTKLEIK

Claims

A method for providing information on the responsiveness of a cancer patient to anticancer therapy, comprising: (a) measuring the level of TCTP in plasma isolated from a cancer patient; and (b) providing information necessary for predicting the responsiveness to anticancer therapy based on the measured plasma TCTP level.

2. A method according to claim 1, wherein the plasma TCTP level measured in step (a) is higher than the reference plasma TCTP level, indicating that the cancer patient has a low responsiveness to anticancer therapy.

3. A method according to claim 1, wherein the anticancer treatment includes chemotherapy.

4. A method according to claim 1, wherein the chemotherapy involves administration of a fluoropyrimidine or platinum, or both.

5. A method according to claim 1, wherein the anticancer therapy includes immunotherapy.

6. A method according to claim 1, wherein the immunotherapy involves administration of an anti-PD-1 antibody.

7. A method according to claim 6, wherein the immunotherapy involves administration of a nivolumab antibody.

8. A method in paragraph 1, wherein the responsiveness is determined by progression-free survival and / or overall survival.

9. A method according to claim 1, further comprising the step of (c) providing information on whether to use a second anticancer therapy for the patient.

10. A method according to claim 9, wherein the second anticancer therapy involves administration of an immunotherapy agent.

11. A method according to claim 9, wherein the second anticancer therapy involves administration of an antibody selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA4 antibody.

12. A method according to claim 9, wherein the second anticancer therapy involves administration of an anti-TCTP antibody.

13. A method according to claim 12, wherein the anti-TCTP antibody is used in combination with an immunotherapy agent.

14. A method according to claim 13, wherein the immunotherapy agent is an antibody selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA4 antibody.

15. A method for increasing the responsiveness of a cancer patient to cancer treatment, comprising the steps of: (a) measuring the level of TCTP in plasma isolated from a cancer patient; (b) providing information necessary for predicting responsiveness to anticancer therapy based on the measured plasma TCTP level; and (c) administering an anticancer therapy comprising an anti-TCTP antibody to a cancer patient having a high plasma TCTP level.

16. A method according to claim 15, wherein the plasma TCTP level measured in step (a) is higher than the reference plasma TCTP level, indicating that the cancer patient has a low response to anticancer therapy.

17. A method according to claim 15, wherein the anticancer treatment comprises chemotherapy.

18. A method according to claim 17, wherein the chemotherapy involves administration of a fluoropyrimidine or platinum, or both.

19. A method according to claim 15, wherein the anticancer therapy comprises immunotherapy.

20. A method according to claim 19, wherein the immunotherapy involves administration of an anti-PD-1 antibody.

21. A method according to claim 19, wherein the immunotherapy involves administration of a nivolumab antibody.

22. A method in claim 15, wherein the responsiveness is determined by progression-free survival and / or overall survival.

23. A pharmaceutical composition for increasing the responsiveness of a cancer patient to cancer treatment, comprising an anti-TCTP antibody.

24. A pharmaceutical composition according to claim 23, wherein the cancer patient is a patient who has previously been administered a chemotherapy agent or an immunotherapy agent.

25. A pharmaceutical composition according to claim 24, wherein the cancer patient shows low responsiveness to a chemotherapy agent or an immunotherapy agent.

26. A pharmaceutical composition according to claim 23, wherein the cancer patient has a plasma TCTP level higher than that of a normal person.

27. A pharmaceutical composition according to claim 23, wherein the anti-TCTP antibody is used in combination with chemotherapy.

28. A pharmaceutical composition according to claim 24, wherein the cancer patient has previously received chemotherapy, wherein the chemotherapy involves administration of a fluoropyrimidine or platinum, or both.

29. A pharmaceutical composition according to claim 24, wherein the cancer patient is a patient who has previously received immunotherapy, and the immunotherapy involves administration of an anti-PD-1 antibody.

30. A pharmaceutical composition according to claim 29, wherein the anti-PD-1 antibody is nivolumab.

31. A pharmaceutical composition according to claim 23, wherein the anti-TCTP antibody is used in combination with immunotherapy.

32. A pharmaceutical composition according to claim 31, wherein the immunotherapy is selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA4 antibody.

33. A pharmaceutical composition according to claim 31, wherein the immunotherapy is an anti-PD-1 antibody.

34. A pharmaceutical composition according to claim 31, wherein the immunotherapy is nivolumab.

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