Use of parasites and extracellular vesicles obtained from parasites in cancer treatment

Patent metadata

Field	Value
Publication number	US-12465623-B2
Application number	US-202017609795-A
Country	US
Kind code	B2
Filing date	May 8, 2020
Priority date	May 10, 2019
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

Abstract

Use of parasites and extracellular vesicles obtained from the parasites for a cancer treatment is provided. The use of parasites and extracellular vesicles obtained from parasites is for using in a treatment of a cancer, and loading an active substance on exosomes by using a drug loading capacity of exosomes, and thus, by carrying a specific drug directly to target cancer cells without causing any side effect on healthy cells and to enhance a bioavailability of the specific drug, achieving a desired effect in a tumor specific target region. Particularly Leishmania infantum parasite is used as a source for the extracellular vesicles.

First claim

What is claimed is:

1 . A pharmaceutical composition for cancer treatment, wherein the composition comprises extracellular vesicles isolated from Leishmania infantum , wherein the extracellular vesicles are isolated from the Leishmania infantum via two-phase liquid system comprising following steps:
collecting a culture media of the Leishmania infantum parasite, wherein the extracellular vesicles are isolated from the parasite, centrifuging at a rate of 2,000 g to 10,000 g for 5-20 minutes for a removal of undesirable substances such as cell residues and the parasite from the culture media, removing particles of size 220 nm and above by a filtration after a centrifugation, transferring a vesicle-protein mixture obtained by the centrifugation into the ATPS containing a PEG phase and a DEX phase for separation f the vesicle-protein mixture, removing non-vesicular proteins, a cello fat and other impurities from the extracellular vesicles by utilizing a chemical tendency of the PEG phase to the non-vesicular proteins and the DEX phase to phospholipid structured membranes, obtaining isolated extracellular vesicles.

2 . The pharmaceutical composition according to claim 1 , comprising at least one active compound selected from the group consisting of active compounds showing an anti parasitic activity, an antibacterial activity, an antiviral activity, antineoplastic activity and/or a cytotoxic activity and/or an antimetastatic activity, and binary and ternary combinations thereof as a further active substance.

3 . The pharmaceutical composition according to claim 2 , comprising at least one agent selected from the group consisting of amikacin, gentamycin, kanamycin, neomycin, netilmicin, tobramycin, paromomycin, streptomycin, spectinomycin, geldanamycin, herbimycin, rifaximin, loracarbef, ertapenem, doripenem, imipenem, meropenem, cephadroxyle, cefazolin, cephalothin, cephalexin, cephaclor, cefamandole, cefoxitin, cefprozil, cefuroxime, cefixime, cefdinir, cefditoren, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, cefepime, ceftaroline fosamil, ceftobiprol, teicoplanin, vancomycin, televancin, dalbavancin, oritavancin, clindamycin, lincomycin, daptomycin, azitromycine, claritromycin, diritromycin, erythromycin, roxithromycin, troleandomycin, telithromycin, spiramycin, aztreonam, furazolidon, nitrofurantoin, linezolid, posizolid, radezolid, torezolid, amoxicillin, ampicillin, azlocillin, carbenicillin, cloxacillin, dicloxacillin, flucoxacillin, mezlocillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, temocillin, ticarcillin, clavulanate, sulbactam, tazobactam, bacitracin, colistin, polymyxin B, ciprofloxacin, enoxacin, gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidinic acid, norfloxacin, ofloxacin, trovafloxacin, grepafloxacin, sparfloxacin, temafloxacin, mafenide, sulfacetamide, sulfadiazine, sulfadimethoxine, sulfamethizole, sulfamethoxazole, sulfanilamide, sulfasalazine, sulfisoxazole, trimethoprim, demeclocycline, doxycycline, minocycline, oxytetracycline, tetracycline, clofazimine, dapsone, capreomycin, cycloserine, ethambutol, isoniazid, pyrazinamide, rifampicin, rifabutin, rifapentine, streptomycin, arsphenamine, chloramphenicol, phosphomycin, fusidic acid, metronidazole, mupirocin, platensimycin, quinupristin, dalfopristin, thiamphenicol, tigecycline, tinidazole, trimethoprim, and binary or ternary combinations and/or encapsulations thereof as the active compound showing the antibacterial activity.

4 . The pharmaceutical composition according to claim 2 , comprising at least one agent selected from the group consisting of abacavir, acyclovir, adefovir, amantadine, amprenavir, ampligen, arbidol, atazanavir, atripla, balavir, sidofovir, kombivir, dolutegravir, darunavir, delavirdin, didanosine, docosanol, eduksudine, efavirenz, emtricitabine, enfuvirtide, entecavir, ecoliver, famciclovir, fomivirsen, fosamprenavir, foscarnet, phosphonet, ganciclovir, ibasitabin, imunovir, idoxuridine, imiquimod, indinavir, inosine, interferon type I, interferon type II, interferon type III, interferon, lamivudine, lopinavir, lovirid, maravirok, moroxidine, methisazone, nelfinavir, nevirapine, nexavir, nitazoxanide, novir, oseltamivir, peginterferon alfa-2a, pensiclovir, peramivir, plekonaril, podofilotoxin, protease inhibitor, nucleoside analogues, ralgetavir, ribavirin, rimantadine, ritonavir, pyramidine, saquinavir, sofoshuvir, stavudine, telaprevir, tenofovir, tipranavir, trifluridine, trisivir, tromantadine, trovada, valaciclovir, valganciclovir, vidarabine, viramidine, zalcitabine, zanamivir, zidovudine, and binary or ternary combinations and/or encapsulations thereof as the active compound showing the antiviral activity.

5 . The pharmaceutical composition according to claim 2 , comprising at least one agent selected from the group consisting of nitazoxanide, melarsoprol, eflornithine, nietronidazol, tinidazole, miltefosine, mebendazole, pyrantel pamoate, thiabendazole, diethylcarbamazine, ivermectin, niclosamide, praziquantel, albendazole, rifampin, amphotericin B, fumagillin, furazolidone, nifursemizone, nitazoxanide, ornidazole, paromomycin sulfate, pentamidine, pirimethamine, tinidazole, albendozole, mebendazole, thiabendazole, fenbendazole, triclabendazole, flubendazole, abomectin, diethylcarbamazine, ivermectin, suramin, pyrantel pamoate, levamisole, niclosamide, nitazoxanide, oxyclozonide, monepantel, derquantel, amphotericin B, urea stibamine, sodium stibogluconate, meglumine antimoniate, paromomycin, miltefosine, fluconazole, pentamidine, and binary or ternary combinations and/or encapsulations thereof as the active compound showing the antiparasitic activity.

6 . The pharmaceutical composition according to claim 2 , comprising at least one agent selected from the group consisting of cyclophosphamide, ifosfamide, temozolomide, capecitabine, 5-fluorouracil, methotrexate, gemcitabine, pemetrexed, mitomycin, bleomycin, epirubicin, doxorubicin, etoposide, paclitaxel, irinotecan, docetaxel, vincristine, carboplatin, cisplatin, oxaliplatin bevacizumab, cetuximab, gefitinib, imatinib, trastuzumab, denosumab, rituximab, sunitinib, zoledronate, abiraterone, anastrozole, bicalutamide, exemestane, goserelin, medroxyprogesterone, octreotide, tamoxifen, bendamustine, carmustine, chlorambucil, lomustine, melphalan, procarbazine, streptozocin, fludarabine, raltitrexed, actinomycin D, dactinomycin, doxorubicin, mitoxantrone, eribulin, topotecan, vinblastine, vinorelbine, afatinib, aflibercept, crizotinib, dabrafenib, interferon, ipilimumab, lapatinib, nivolumab, panitumumab, pembrolizumab, pertuzumab, sorafenib, trastuzumab emtansine, temsorilimus, vemurafenib, ibandronic acid, pamidronate, bexarotene, buserelin, cyproterone, degarelix, folinic acid, fulvestrant, lanreotide, lenalidomide, letrozole, leuprorelin, megestrol, mesna, thalidomide, vincristine, and binary or ternary combinations and/or encapsulations thereof as the active compound showing the antineoplastic activity in combination with the extracellular vesicles and/or the nano-carrier systems.

7 . The pharmaceutical composition according to claim 2 , comprising at least one active substance.

8 . The pharmaceutical composition according to claim 2 , wherein the composition is administered by parenteral, intravenous, intradermal, subcutaneous, intraperitoneal, topical, intrathecal, intranasal, intracerebroventricular, ocular, vaginal, urethral, transdermal, sublingual, subarachnoid, rectal, periodontal, perineural, peridural, periarticular, oral, intratympanic, intratumor, intrapulmonary, intrasynovial, intramuscular, intraovarian, intrameningeal, intracorporus cavernosum, intracoronary, intracerebral, epidural, cutaneous, bucc

Assignees

• Univ Yeditepe

Inventors

• Sahin Fikrettin
• Islek Zeynep
• Taskan Ezgi
• Tasli Pakize Neslihan
• Bozkurt Batuhan Turhan
• Kirbas Oguz Kaan
• Ucisik Mehmet Hikmet

Classifications

• A61K2039/55588

  Adjuvants of undefined constitution · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• A61K39/008

  Leishmania antigens · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title