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Cytokine immunotherapy of cancer with controlled release biodegradable microspheres in a human tumor xenograft/SCID mouse model |
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| Authors: | N. K. Egilmez Yong S. Jong Yoshimi Iwanuma Jules S. Jacob Camilla A. Santos Fang-An Chen Edith Mathiowitz Richard B. Bankert |
| Affiliation: | (1) Department of Molecular Immunology, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA, US;(2) Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, 69 Brown Street, Providence, RI 02912, USA, US;(3) Juntendo University School of Medicine, First Department of Surgery, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113, Japan, JP |
| Abstract: | A novel biodegradable poly(lactic acid) microsphere formulation was evaluated for in vivo cytokine immunotherapy of cancer in a human tumor xenograft/severe combined immunodeficiency (SCID) mouse model. Co-injection of interleukin-2 (IL-2)-loaded microspheres with tumor cells into a subcutaneous site resulted in the complete suppression of tumor engraftment in 80% of animals. In contrast, bovine-serum-albumin(BSA)-loaded particles or bolus injections of poly(ethylene glycol)/IL-2 were ineffective in preventing tumor growth. The antitumor effect of IL-2 released by the microspheres was shown to be mediated by the mouse natural killer cells. This is the first evidence that the rejection of human tumor xenografts can be provoked by the sustained in vivo delivery of IL-2 from biodegradable microspheres. The use of poly(lactic acid) microspheres to deliver cytokines to the tumor environment could provide a safer and simpler alternative to gene therapy protocols in the treatment of cancer. Received: 9 September 1997 / Accepted: 30 October 1997 |
| Keywords: | Cancer immunotherapy Cytokines Biodegradable microspheres SCID mice Human tumors |
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