Abstract
Abstract Background: In order to develop more effective anticancer agents there is a shift from not only treating the bulk of cells in a tumor but also to target the self renewing cancer stem cells (CSCs). Standard treatment with chemotherapy and radiotherapy is unable to eradicate CSCs and therefore other treatment modalites against CSCs are needed. LTX-315 (Oncopore®) is a chemically modified cytolytic peptide which is equally active against drug-sensitive and drug-resistant cancer cells. Earlier animal studies have demonstrated that treatment of syngenic murine A20 B-lymphomas and CT26WT carcinomas with intratumoral (i.t.) injection with LTX-315 resulted in complete tumor regression. The present study was undertaken to investigate whether LTX-315 induced an antitumor response in vivo in a novel malignant rat mesenchymal tumor model with “stemness” properties. Methods: Following long-term culturing of bone marrow-derived rat mesenchymal cells, a transformed mesenchymal cell line (rTMSC) has been been developed. rTMSC has, as the non-malignant rMSC, maintained osteogenic and adipose differentation properties and side population cells from rTMSC are highly clonogenic both in vitro and in vivo. Previously we have shown that s.c. as well as i.v. or i.p. injection of rTMSCs form immature solid sarcomas both in nude rats as well as in PVG rats. In this study the rTMSCs were marked with a dual reporter gene GFP and Luciferase and a CCD camera was used for dynamic living imaging. rTMSCs (5×105 cells) were subcutaneously inoculated into PVG rats and established tumors treated i.t. with LTX-315. Results: Intratumoral treatment with LTX-315 resulted in a complete regression in the majority of the treated animals. Successfully treated mice were protected against s.c. or i.p. re-challenge with rTMSCs. Conclusions: Taken together, our results suggest that LTX-315 treatment induced complete regression and long-term, specific cellular immunity against malignant rat mesenchymal tumor cells with “stemness” properties”. Thus, intratumoral administration of a cytolytic peptide might, in addition to providing local tumor control, confer a novel strategy for therapeutic vaccination against established cancers containing CSCs Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-161. doi:10.1158/1538-7445.AM2011-LB-161
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