Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
  • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
  • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
  • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
  • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
  • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
  • A61K47/6817—Toxins
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents

Definitions

• Cytotoxic drug formed from the combination of at least one immunotoxin and chloroquine.
• the present invention relates to medicaments comprising, in combination, at least one immunotoxin and chloroquine.
• the present invention relates to the preparation of potent cytotoxic drugs using the potentiating of the selective cytotoxic effects of the immunotoxins described in the patent applications mentioned above.
• This example demonstrates the potentiation of the selective cytotoxicity of the anti-T65 immunotoxin (as described in application n ° 8121 836 of the applicant) with respect to human T lymphoblastoid cells of the CEM line carrying the T65 antigen .
• Figure 2 shows the comparative potentiating effect of the NH 4 + ion (10 mM) and chloroquine (60, uM) on the cytotoxicity of the anti-T65 imm unotoxin with respect to the cells of the line. EMC.
• the values of the molar concentrations (IC50) corresponding to 50% inhibition of incorporation of the tracer are given in Table II.
• chloroquine has the remarkable property not only of potentiating the activity but also of increasing the selectivity of the immunotoxin. If we take as a criterion of selectivity of action of the immunotoxin the ratio of IC50s of the free A chain and of the immunotoxin, this ratio is 10 in the absence of chloroquine and close to 44,000 in presence of chloroquine.
• chloroquine is not limited to considerably increasing the cytotoxic activity and the selectivity of immunotoxins. This substance also makes it possible to accelerate very significantly the kinetics of cytotoxicity of the immunotoxins, as the following experiment shows:
• the combination of immunotoxin and chloroquine can therefore be used as a medicament in human therapy. It can be used for the treatment of conditions, cancerous or not, which are sensitive to the antibody used for the preparation of the immunotoxin. Aiming at eliminating all the cancer cells, the treatment should be carried out with a sufficient dose of immunotoxin associated with an amount of chloroquine which can vary from 10 mg to 2 g (expressed in base) with each administration of immunotoxin. The duration of treatment should be determined in each case depending on the subject and the nature of the condition to be treated.
• the new drugs according to the invention are packaged so that they can be used under the conditions suitable for their use.
• the immunotoxin will be administered by injection and preferably by intravenous route. Chloroquine should preferably be administered by injectable route unless its oral use has therapeutic advantages.

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• Health & Medical Sciences (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• Life Sciences & Earth Sciences (AREA)
• Public Health (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Veterinary Medicine (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Epidemiology (AREA)
• Molecular Biology (AREA)
• Toxicology (AREA)
• Immunology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Medicines Containing Material From Animals Or Micro-Organisms (AREA)
• Steroid Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=9271836

Family Applications (1)

Country Status (8)

Cited By (1)

Families Citing this family (6)

Citations (1)

Family Cites Families (1)

• 1982
  • 1982-03-10 FR FR8204047A patent/FR2522968B1/fr not_active Expired
• 1983
  • 1983-03-07 JP JP58500899A patent/JPS59500370A/ja active Granted
  • 1983-03-07 US US06/552,052 patent/US4582703A/en not_active Expired - Fee Related
  • 1983-03-07 AT AT83400459T patent/ATE20519T1/de not_active IP Right Cessation
  • 1983-03-07 DE DE8383400459T patent/DE3364240D1/de not_active Expired
  • 1983-03-07 EP EP83400459A patent/EP0088694B1/fr not_active Expired
  • 1983-03-07 WO PCT/FR1983/000044 patent/WO1983003055A1/fr not_active Ceased
  • 1983-11-09 NO NO834087A patent/NO834087L/no unknown

Patent Citations (1)

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