Recombinant human endostatin adenovirus(Chengdu Enduoshi Biological Engineering Technology Co Ltd)

To investigate the antitumor effect of recombinant Endostatin adenovirus (Ad-E) with carboplatin in mice with Lewis lung cancer.

C57BL/6 mice bearing Lewis lung cancer received Ad-E and carboplatin respectively or in combination. The tumor volume, tumor net weight, survival time and side effects were observed. Histological analysis was conducted to assess microvessel density (MVD) within tumor tissue and apoptotic cells were identified using the TUNEL assay.

Compared with the control groups, the combination treatment significantly suppressed the tumor growth and prolonged survival time of the mice without obvious side-effects. The histological analysis revealed the combination treatment led to a decreased MVD and increased percent apoptosis in LL/2 tumors.

Our studies indicate that a combination of Ad-E with carboplatin can present better antitumor effects without obvious side-effect.

Recently, some phase I trials on endostatin has shown broad antitumor activity with low toxicity. This study was to determine the maximal tolerant dose (MTD) of recombinant human endostatin adenovirus Ad-Es for human.

For the sake of safety, 1 patient was treated with 1x10(10) VP Ad-Es single intratumoral injection in advance. A total of 14 patients with malignant tumors received weekly intratumoral injection of Ad-Es in a dose-escalation manner (1x10(11) VP, 5x10(11) VP, 1x10(12) VP) for 2 weeks.

Toxicity profiles in all 15 cases were available. All patients tolerated well. No dose-limited toxicity (DLT) and serious adverse event were observed during treatment. Main adverse events were injection reaction (40.0%) and fever (53.3%). One patient with nasopharyngeal carcinoma had a minor response, 12 patients showed stable disease and 2 patients had progressive disease.

Ad-Es is well tolerated up to 1x10(12) VP. The recommended dose for phase II trial is 1x10(12) VP intratumor injection for 4 consecutive weeks.