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Encapsulation of c-myc antisense oligodeoxynucleotides in lipid particles improves antitumoral efficacy in vivo in a human melanoma line

Cancer Gene Therapy volume 8, pages 459–468 (2001)Cite this article

Abstract

Phosphorothioate c-myc antisense oligodeoxynucleotides [S]ODNs (free INX-6295) were encapsulated in a new liposome formulation and the antitumor activity was compared to the unencapsulated antisense in a human melanoma xenograft. The systemic administration of INX-6295 encapsulated in stabilized antisense lipid particles (SALP INX-6295) improved plasma AUC (area under the plasma concentration–time curve) and initial half-life of free INX-6295, resulting in a significant enhancement in tumor accumulation and improvement in tumor distribution of antisense oligodeoxynucleotides. Animals treated with SALP INX-6295 exhibited a prolonged reduction of c-myc expression, reduced tumor growth and increased mice survival. When administered in combination with cisplatin (DDP), SALP INX-6295 produced a complete tumor regression in approximately 30% of treated mice, which persisted for at least 60 days following the first cycle of treatment. Finally, the median survival of mice treated with DDP/SALP INX-6295 increased by 105% compared to 84% for animals treated with the combination DDP/free INX-6295. These data indicate that the biological activity and the therapeutic efficacy of c-myc antisense therapy may be improved when these agents are administered in lipid-based delivery systems. Cancer Gene Therapy (2001) 8, 459–468

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Acknowledgements

Barbara Benassi is recipient of a fellowship from Italian Foundation for Cancer Research (FIRC).

The authors thank Marco Scarsella for expert technical assistance in animal experiments, Simona Righi for excellent secretarial support, and Mauro Di Giovanni for photographic assistance.

This work was partially supported by Italian Association for Cancer Research (AIRC), Ministero della Sanità, and Progetto Strategico Murst-CNR.

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Authors and Affiliations

  1. Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, 00158, Italy

    Carlo Leonetti, Annamaria Biroccio, Barbara Benassi & Gabriella Zupi

  2. Ultrastructures Department, Istituto Superiore di Sanità, Rome, Italy

    Annarita Stringaro

  3. Department of Experimental Medicine and Pathology, II Faculty, S. Andrea, Rome, Italy

    Antonella Stoppacciaro

  4. Inex Pharmaceuticals Corp., Burnaby, BC, Canada

    Sean C Semple

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  1. Carlo Leonetti
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Correspondence to Carlo Leonetti.

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Leonetti, C., Biroccio, A., Benassi, B. et al. Encapsulation of c-myc antisense oligodeoxynucleotides in lipid particles improves antitumoral efficacy in vivo in a human melanoma line. Cancer Gene Ther 8, 459–468 (2001). https://doi.org/10.1038/sj.cgt.7700326

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