ZASTOSOWANIE PRODUKTÓW MIKROORGANIZMÓW
W TERAPIACH ANTYNOWOTWOROWYCH
Katarzyna Łepeta1, Anna Maria Łasica1,
Elżbieta Katarzyna Jagusztyn-Krynicka1*
1Zakład Genetyki Bakterii, Wydział Biologii, UW, ul. Miecznikowa 1, 02-096 Warszawa
00-096 Warszawa, ul. Miecznikowa 1
Wpłynęło w lipcu 2010 r.
1. Wstęp. 2. Antynowotworowa aktywność toksyny wąglika. 3. Immunotoksyny. 3.1. Budowa i mechanizm działania toksyny dyfterytu i egzotoksyny A Pseudomonas aeruginosa. 3.2. Testy kliniczne wybranych immunotoksyn. 3.3. Problemy terapii z zastosowaniem immunotoksyn. 4. Bakteryjne białka o aktywności antynowotworowej. 4.1. Azuryna. 4.2. NPI-0052. 5. Zastosowanie niemetylowanych bakteryjnych dinukleotydów CpG, agonistów TLR9, w terapiach antynowotworowych. 6. Podsumowanie
Application of microorganism products in antitumor therapies
Abstract: One of the main goals of alternative anticancer therapies is to find a method that would allow selective tumor cells targeting. One of such methods is based on application of microorganism products. Many bacterial proteins have been investigated as potential antitumor agents. Among them - azurin, one of a class of copper-containing proteins called blue-copper proteins and NPI-0052 (salinisporamide A), proteasome inhibitor that was isolated from Salinispora tropica. Many tumor cells overexpress particular proteins, such as MMPs (Matrix metalloproteinases) or uPAR (urokinase type plasminogen activator receptor). This feature of tumor cells was used for applying in anticancer therapies anthrax toxin, exotoxin secreted by virulent strains of Bacillus anthracis. By replacing the native furin cleavage site in anthrax toxin-protective antigen by that recognized by MMP, it is possible to selectively target tumor cells. The third main application of microbial products in cancer treatment are immunotoxins, which are proteins that contain a modified toxin linked to an antibody. Also modified bacterial toxins fused to growth factor or cytokines that bind selectively to target cells are potential new anticancer drugs.
1. Introduction. 2. 0Antitumor avtivity of anthrax toxin. 3. Immunotoxins. 3.1. Structure and mechanism of action of diphtheria toxin and Pseudomonas aeruginosa exotoxin A. 3.2. Clinical tests of chosen immunotoxins. 3.3. Immunotoxin therapy problems. 4. Bacterial proteins of antitumor activity. 4.1. Azurin. 4.2. NPI-0052. 5. Application of methylated bacterial dinucleotides CpG, TLR9 agonists, in antitumor therapy 6. Summary
Słowa kluczowe: immunotoksyny, mikroorganizmy, nowotwór, toksyna wąglika
Key words: immunotoxins, microorganisms, tumor, anthrax toxin
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