Sammendrag
Background: LTX-315 (Oncopore) is a chemically designed cationic nonapeptide derived from a natural host defensive CAP, bovine lactoferricin (LfcinB) in development for local treatment of tumours. Earlier studies have demonstrated that treatment of A20 lymphomas and CT26WT carcinomas with LTX-315 in immunocompetent mice resulted in tumour regression. Re-challenge with tumor cells in the cured animals showed that a long- term protection was induced against the tumor.
Methods: In the current experiments we have investigated if LTX-315 also can have the same effect on a novel established malignant rat mesenchymal tumor cell line with “stemness” properties. Following long term culturing of bone marrow derived rat mesenchymal cells we developed a rat transformed mesenchymal cell line (rTMSC). Previously we have shown that s.c. as well as i.v. and i.p. injection of rTMSC form immature sarcoma tumors both in nude rats as well as in PVG rats. The rTMSC has been stabled marked with a dual reporter gene GFP and Leuciferase and in the current study CCD camera was used for dynamic living imaging. 5×105 rTMSCs were subcutaneously inoculated into 20 PVG rats. After 7 days measurable tumors could be observed and 18 animals was treated with LTX-315.
Results: In spite of repeated injection with the peptide 8 animals lost tumor control, while 9 animals within 38 days achieved complete tumor responses as assessed with CCD camera. Re-challenges of the tumor free animals with injection of 5×104 tRMSCs show no tumor growth while all control animals had a fast tumor formation.
Conclusions: 50% of the treated animals have developed an impressive tumor protection of this aggressive mesenchymal tumor with “stemness” properties. Most likely more animals can be cured if the peptide injection procedure can be improved and further studies are underway. Altogether our results bear promises for LTX-315 in future cancer therapy.
No significant financial relationships to disclose.
© 2010 by American Society of Clinical Oncology
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