Tgen hasn't listed any 2001 papers on their website yet...
targetedgenetics.com
...but here is an abstract for tgdcce1a.
If anybody sees anything exciting, do speak up. The first
abstract sounded promising...but the second shows results
that seem, to me, underwhelming.
J Clin Oncol 2001 Jul 15;19(14):3422-33
Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer
cells and its biologic effects: a phase I clinical trial.
Hortobagyi GN, Ueno NT, Xia W, Zhang S, Wolf JK, Putnam JB, Weiden PL, Willey
JS, Carey M, Branham DL, Payne JY, Tucker SD, Bartholomeusz C, Kilbourn RG, De
Jager RL, Sneige N, Katz RL, Anklesaria P, Ibrahim NK, Murray JL, Theriault RL,
Valero V, Gershenson DM, Bevers MW, Huang L, Lopez-Berestein G, Hung MC.
Department of Breast Medical Oncology, The University of Texas M.D. Anderson
Cancer Center, Houston, TX 77030, USA. ghorto@notes.mdacc.tmc.edu
PURPOSE: Preclinical studies have demonstrated that the adenovirus type 5 E1A
gene is associated with antitumor activities by transcriptional repression of
HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to
induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude
mice. Therefore, we evaluated the feasibility of intracavitary injection of E1A
gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both
HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers
in a phase I clinical trial. PATIENTS AND METHODS: An E1A gene complexed with
DCC-E1A cationic liposome was injected once a week into the thoracic or
peritoneal cavity of 18 patients with advanced cancer of the breast (n = 6) or
ovary (n = 12). RESULTS: E1A gene expression in tumor cells was detected by
immunohistochemical staining and reverse transcriptase-polymerase chain
reaction. This E1A gene expression was accompanied by HER-2/neu downregulation,
increased apoptosis, and reduced proliferation. The most common
treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at
the injection sites. CONCLUSION: These results argue for the feasibility of
intracavitary DCC-E1A administration, provide a clear proof of preclinical
concept, and warrant phase II trials to determine the antitumor activity of the
E1A gene.
................
targetedgenetics.com
another...
Clin Cancer Res 2001 May;7(5):1237-45
Phase I trial of intratumoral liposome E1A gene therapy in patients with
recurrent breast and head and neck cancer.
Yoo GH, Hung MC, Lopez-Berestein G, LaFollette S, Ensley JF, Carey M, Batson E,
Reynolds TC, Murray JL.
Departments of Otolaryngology-Head and Neck Surgery, Wayne State
University-Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
PURPOSE: We conducted a Phase 1 study to determine the maximal tolerated dose
and maximum biologically active dose of the E1A gene delivered by intratumoral
injection as a lipid complex with 3
beta[N-(n',n'-dimethylaminoethane)-carbamoyl]
cholesterol/dioleoylphosphatidyl-ethanolamine (tgDCC-E1A). The E1A adenovirus
gene functions as a tumor inhibitor gene by repressing oncogene transcription;
modulating gene expression, resulting in cellular differentiation; and inducing
apoptosis of cancer cells. E1A also sensitizes cancer cells to chemotherapeutic
drugs such as etoposide, cisplatin, and taxol. EXPERIMENTAL DESIGN: Nine
patients with recurrent and unresectable breast cancer and nine patients with
head and neck cancer were enrolled. One tumor nodule in each patient was
injected with tgDCC-E1A. Safety, tumor response, E1A gene transfer, and
down-regulation of HER-2/neu were evaluated. RESULTS: No dose-limiting toxicity
was observed in the four dose groups (15, 30, 60, and 120 microg DNA/cm of
tumor). All patients tolerated the injections, although several experienced pain
and bleeding at the injection site. A maximally tolerated dose was not reached
in this study. E1A gene transfer was demonstrated in 14 of 15 tumor samples
tested, and down-regulation of HER-2/neu was demonstrated in two of the five
patients who overexpressed HER-2/neu at baseline. HER-2/neu could not be
assessed in other posttreatment tumor samples because of extensive necrosis. In
one breast cancer patient, no pathological evidence of tumor was found on biopsy
of the treated tumor site at week 12. In 16 patients evaluable for tumor
response, 2 had minor responses, 8 had stable disease, and 6 had progressive
disease. CONCLUSIONS: Gene therapy with an E1A gene:lipid complex appears to be
safe and warrants further testing.
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