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Combination of anticancer peptide (CAMEL) with immunotherapy in B16(F10) murine melanoma tumor therapy

Ryszard Smolarczyk 1Tomasz Cichoń 1Wojciech Kamysz 2Magdalena Głowala-Kosińska 3Anna Szydło 4Rafał Nadolny 2Stanisław Szala 1

1. Zakład Biologii Molekularnej Centrum Onkologii-Instytut im. M. Skłodowskiej-Curie oddz. Gliwice, Wybrzeże Armii Krajowej 15, Gliwice 44-101, Poland
2. Akademia Medyczna Gdańsk Wydział Farmacji (AMG), Gen. J. Hallera 107, Gdańsk 80-416, Poland
3. Centrum Onkologii-Instytut im. M.Skłodowskiej-Curie Oddział w Gliwicach (I.O.), Al. Wybrzeża AK15, Gliwice 44-101, Poland
4. Department of General, Molecular Biology and Genetics, Medical University of Silesia, Medyków 18, Katowice 40-752, Poland

Abstract

Peptide KWKLFKKIGAVLKVL (CAMEL) is a hybryd molecule combining two peptide fragments: that of Cecropin A (aminoacids 1-7) and Mellitin (aminoacids 2-9). The fusion peptide is a potent antibacterial drug.
We tried to investigate whether CAMEL could be used in anticancer therapy.
We assessed in vitro the effectiveness of peptide action against B16F(10), NIH3T3 and HeCa10 cells. Independently of the cell type the peptide was cytotoxic and its LC50 was 3μM.
Following administration to cells the peptide probably induced their necrotic death.
Therapeutic experiments demonstrated a marked inhibition of tumor growth following CAMEL administration to B16(F10) murine melanoma tumor-bearing C57BL/6 mice. Tumor growth inhibition was sustained as long as the peptide was administered. Three to four days after therapy cessation intensive tumor growth was resumed.
Neoplastic cells that survived CAMEL therapy appear to have been responsible for this regrowth. In order to obtain total tumor eradication we decided to combine CAMEL therapy with immunotherapy. As immunostimulatory factor we used plasmid DNA bearing IL-12 gene and oligonucleotides with unmethylated CpG sequences.
The combination of CAMEL peptide with immunostimulatory agents led to considerably improved tumor growth inhibition and statistically significant extension of animal survival, in some cases their complete cure.

 

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Presentation: Poster at Zjazd Polskiego Towarzystwa Biochemicznego, Sympozjum E, by Ryszard Smolarczyk
See On-line Journal of Zjazd Polskiego Towarzystwa Biochemicznego

Submitted: 2007-04-27 09:36
Revised:   2009-06-07 00:44