>>FRAMINGHAM, Mass., Oct. 29 /PRNewswire-FirstCall/ -- In a scientific journal article published this month, a group of research scientists with Genzyme Molecular Oncology (Nasdaq: GZMO - News) report that immune- stimulating complexes made up of lipid and plasmid DNA produced immune responses that caused significant tumor regression in mice. The pre-clinical study findings also suggest these effects may extend long-term survival.
Johanne M. Kaplan, Ph.D., and William M. Siders, Ph.D., of Genzyme Molecular Oncology collaborated with other Genzyme Corp. researchers on the melanoma study. Their article, "Tumor Treatment with Complexes of Cationic Lipid and Noncoding Plasmid DNA Results in the Induction of Cytotoxic T Cells and Systemic Tumor Elimination," appears in the October edition of Molecular Therapy.
Findings from the research study show a significant, immune system response occurs within 24 hours following injection with these lipid/DNA complexes into, or near, the tumor site. Although the sequence of events is still undefined, the complex appears to initiate a chain of events that charges up the immune system and kills cancer cells not only located at the point of injection, but also at locations throughout the body where metastases had occurred. The study further suggests that these lipid/DNA complexes may provide a long-term survival benefit because once rejected, the cancer tumor does not recur in a majority of the study mice.
According to the study, what further makes these complexes unique is their ability to spark an antigen-specific immune response without the need for antigens. Findings suggest DNA/lipid complexes may represent a potentially useful approach for treating a broad range of cancer types.
"This new approach represents a potent and practical way to trigger an increase in the natural immune response in the injected tumor area, and set in motion the development of a specific anti-tumor response that can reach out and destroy tumor cells throughout the body," stated Kaplan. "Achieving an antigen-specific response without the use or need for antigens could prove to be a major development in how cancer vaccines are produced in the future. We are very excited by these findings and encouraged about the opportunity that may exist to develop this approach further."
The study also reveals that mice mount a natural anti-tumor response, but that this response is not sufficient by itself to regress tumors. Once enhanced by this lipid/DNA complex, the immune response may become strong enough to shrink the tumors and provide long-term survival benefit. Pre- clinical data from seven separate studies showed 100 percent, long-term survival of between 30 and 70 days in a melanoma tumor model.
Kaplan and her colleagues state that additional studies are now needed to determine if these complexes would be more useful as a standalone therapy, or in combination with antigen specific vaccines.<<
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>>Mol Ther 2002 Oct;6(4):519
Tumor treatment with complexes of cationic lipid and noncoding plasmid DNA results in the induction of cytotoxic T cells and systemic tumor elimination.
Siders W, Vergillis K, Johnson C, Scheule R, Kaplan J.
Genzyme Molecular Oncology, Framingham, Massachusetts, 01701, USA
We have demonstrated recently that treatment of established peritoneal mesothelial tumors with complexes composed of cationic lipid and noncoding plasmid DNA (pNull) results in the inhibition of tumor growth accompanied by the induction of a tumor-specific cellular immune response. In this study, treatment of mice bearing intraperitoneal (i.p.) M3 melanoma tumors with i.p. injections of lipid/pNull complex was found to inhibit tumor growth and induce the development of a cytolytic response against several M3 melanoma-associated antigens. Depletion of CD8(+) T cells, as opposed to natural killer (NK) or CD4(+) T cells, essentially abrogated the therapeutic effect of lipid+pNull complex, thus supporting the involvement of cytotoxic CD8(+) T cells in the antitumor response. The antitumor effect of lipid/pNull complex was maximal following delivery into a tumor-bearing compartment. For example, i.p. delivery of complex was more effective than intravenous (i.v.) or subcutaneous (s.c.) treatment of i.p. M3 tumors. In addition, i.v. injection of complex displayed therapeutic activity against lung metastases caused by i.v. injection of tumor cells, and intratumoral injection of complex into solid s.c. tumors caused regression in most animals. Importantly, the immune response induced by local treatment of tumors with complex also offered systemic protection against tumor cells at distal sites, as illustrated by the eradication of both peritoneal tumors and lung metastases in mice treated with complex delivered i.p. Treatment with lipid/pNull complex, therefore, represents an attractive immune-based treatment modality that could potentially be applied to many tumor types.<<
Cheers, Tuck |
