Cell therapeutic agent for cancer treatment and combination therapy with same

Abstract

The present disclosure relates to a method for preparing cells for cancer treatment and a kit for cancer treatment comprising cells prepared by the method. The preparation method of the present disclosure can provide F cells, which, in spite of having no difference in the proliferative capacity compared with mesenchymal stem cells expressing cytosine deaminase that are harvested and used immediately after the culture, exhibit a very excellent tumor suppressive effect through the treatment together with 5-FC and induce a remarkable synergistic effect exceeding an effect from combinative treatment with an existing anticancer drug in cases of a combinative treatment with another anticancer drug. Therefore, the present disclosure can be utilized for a kit for cancer treatment comprising such F cells, and thus can be favorably used to maximize the effect of existing cancer treatments.

1 . A method for preparing F cells comprising: 1) introducing cytosine deaminase (CD) into a mesenchymal stem cell (MSC) to prepare mesenchymal stem cell/cytosine deaminase (MSC/CD); 2) freezing the prepared MSC/CD to prepare frozen MSC/CD; and 3) thawing and suspending the frozen MSC/CD to prepare F cells. 
     
     
         2 . The method according to  claim 1 , wherein the F cell(s) is not subjected to cell culturing after freezing. 
     
     
         3 . The method according to  claim 1 , wherein the F cell(s) is used for cancer treatment. 
     
     
         4 . The method according to  claim 3 , wherein the cancer is at least one selected from the group consisting of squamous cell cancer, small cell lung cancer, non-small cell lung cancer, lung cancer, peritoneal cancer, colorectal cancer, biliary tumor, nasopharyngeal cancer, laryngeal cancer, bronchial cancer, oral cancer, osteosarcoma, gallbladder cancer, kidney cancer, leukemia, bladder cancer, melanoma, brain cancer, glioma, brain tumor, skin cancer, pancreatic cancer, breast cancer, liver cancer, bone cancer, esophageal cancer, colon cancer, gastric cancer, cervical cancer, prostate cancer, ovarian cancer, head and neck cancer, and rectal cancer. 
     
     
         5 . The method according to  claim 1 , wherein the F cell(s) is an adjuvant for anti-cancer. 
     
     
         6 . An adjuvant for anti-cancer comprising the F cells prepared by the method according to  claim 1 . 
     
     
         7 . A kit for cancer treatment comprising the F cells prepared by the method according to  claim 1 , and 5-fluorocytosine (5-FC). 
     
     
         8 . The kit according to  claim 7 , further comprising an anti-cancer agent. 
     
     
         9 . The kit according to  claim 8 , wherein the anti-cancer agent is at least one selected from the group consisting of nitrogen mustard, imatinib, oxaliplatin, rituximab, elotinib, trastuzumab, gefitinib, bortezomib, sunitinib, carboplatin, sorafenib, bevacizumab, cetuximab, viscum album, asparaginase, tretinoin, hydroxycarbamide, dasatinib, estramustine, gemtuzumab ozogamicin, ibritumomab tiuxetan, heptaplatin, methylaminolevulinic acid, amsacrine, alemtuzumab, procarbazine, alprostadil, holmium nitrate chitosan, gemcitabine, doxifluridine, pemetrexed, tegafur, capecitabine, gimeracil, oteracil, azacytidine, cytarabine, fludarabine, enocitabine, decitabine, mercaptopurine, thioguanine, cladribine, carmofur, raltitrexed, docetaxel, paclitaxel, belotecan, topotecan, vinorelbine, etoposide, vincristine, vinblastine, tenifocide, idarubicin, epirubicin, mitoxantrone, mitomycin, bleomycin, daunorubicin, dactinomycin, pirarubicin, aclarubicin, pepromycin, temozolomide, busulfan, ifosfamide, cyclophosphamide, melphalan, altretamine, dacarbazine, thiotepa, nimustine, chlorambucil, mitolactol, taxotere, gleevec, taxol, herceptin, tarceva, avastin, zoladex, adriamycin, irinotecan, 10058-F4, cisplatin, cyclophosphamid, nitrosourea-based anti-cancer agent, methotrexate, carmustine (BCNU), lomustine (CCNU), and doxorubicin. 
     
     
         10 . A method for preventing or treating cancer comprising: 1) introducing cytosine deaminase (CD) into a mesenchymal stem cell (MSC) to prepare mesenchymal stem cell/cytosine deaminase (MSC/CD);
 2) freezing the prepared MSC/CD to prepare frozen MSC/CD;   3) thawing and suspending the frozen MSC/CD to prepare F cells;   4) administering the F cells to a subject in need of treatment; and   5) administering 5-fluorocytosine (5-FC) to a subject in need of treatment.   
     
     
         11 . The method according to  claim 10 , further comprising 6) administering an anti-cancer agent to a subject in need of treatment. 
     
     
         12 . The method according to  claim 10 , further comprising administering an anti-cancer agent to a subject in need of treatment before administration of the F cells according to step 4) or simultaneously with administration of the F cells according to step 4). 
     
     
         13 . The method according to  claim 11 , wherein the anti-cancer agent is at least one selected from the group consisting of nitrogen mustard, imatinib, oxaliplatin, rituximab, elotinib, trastuzumab, gefitinib, bortezomib, sunitinib, carboplatin, sorafenib, bevacizumab, cetuximab, viscum album, asparaginase, tretinoin, hydroxycarbamide, dasatinib, estramustine, gemtuzumab ozogamicin, ibritumomab tiuxetan, heptaplatin, methylaminolevulinic acid, amsacrine, alemtuzumab, procarbazine, alprostadil, holmium nitrate chitosan, gemcitabine, doxifluridine, pemetrexed, tegafur, capecitabine, gimeracil, oteracil, azacytidine, cytarabine, fludarabine, enocitabine, decitabine, mercaptopurine, thioguanine, cladribine, carmofur, raltitrexed, docetaxel, paclitaxel, belotecan, topotecan, vinorelbine, etoposide, vincristine, vinblastine, tenifocide, idarubicin, epirubicin, mitoxantrone, mitomycin, bleomycin, daunorubicin, dactinomycin, pirarubicin, aclarubicin, pepromycin, temozolomide, busulfan, ifosfamide, cyclophosphamide, melphalan, altretamine, dacarbazine, thiotepa, nimustine, chlorambucil, mitolactol, taxotere, gleevec, taxol, herceptin, tarceva, avastin, zoladex, adriamycin, irinotecan, 10058-F4, cisplatin, cyclophosphamid, nitrosourea-based anti-cancer agent, methotrexate, carmustine (BCNU), lomustine (CCNU), and doxorubicin. 
     
     
         14 . The method according to  claim 10 , wherein the F cells of step 4) and the 5-fluorocytosine of step 5) are administered simultaneously or sequentially. 
     
     
         15 . The method according to  claim 11 , wherein the 5-fluorocytosine of step 5) and the anti-cancer agent of step 6) are administered simultaneously or sequentially. 
     
     
         16 . The method according to  claim 11 , wherein the administration of the F cells according to step 4) is repeated with a cycle of 10 to 30 days. 
     
     
         17 . The method according to  claim 10 , wherein the cancer is at least one selected from the group consisting of squamous cell cancer, small cell lung cancer, non-small cell lung cancer, lung cancer, peritoneal cancer, colorectal cancer, biliary tumor, nasopharyngeal cancer, laryngeal cancer, bronchial cancer, oral cancer, osteosarcoma, gallbladder cancer, kidney cancer, leukemia, bladder cancer, melanoma, brain cancer, glioma, brain tumor, skin cancer, pancreatic cancer, breast cancer, liver cancer, bone cancer, esophageal cancer, colon cancer, gastric cancer, cervical cancer, prostate cancer, ovarian cancer, head and neck cancer, and rectal cancer.