A Phase I trial of TNFerade biologic in patients with soft tissue sarcoma in the extremities.

Purpose: TNFerade is a second-generation replication-deficient adenovector carrying a transgene encoding human tumor necrosis factor alpha under control of a radiation- induced promoter. The objective of this study was to assess the tolerance of combining TNFerade and radiation therapy in patients with soft tissue sarcomas of the extremity.

Experimental Design: TNFerade was administered in combination with single-daily fractionated radiation therapy in 14 patients with soft tissue sarcoma of the extremities.

VEGF gene therapy for coronary artery disease and peripheral vascular disease.

Coronary artery disease (CAD) and peripheral arterial disease (PAD) are significant medical problems worldwide. Although substantial progress has been made in prevention as well as in the treatment, particularly of CAD, there are a large number of patients, who despite maximal medical treatment have substantial symptomatology and who are not candidates for mechanical revascularization. Therapeutic angiogenesis represents a novel, conceptually appealing treatment option.

Angiogenic gene therapy strategies for the treatment of cardiovascular disease.

Coronary artery disease (CAD) and peripheral vascular disease (PVD) are significant medical problems worldwide, and arguably the biggest medical problems in the developed world. Although substantial progress has been made in prevention as well as in the treatment of these diseases, particularly of CAD, there are a large number of patients, who despite maximal medical treatment, have substantial symptomatology, and who are not candidates for mechanical revascularization. Therapeutic angiogenesis represents a novel, conceptually appealing, treatment option for these patients.

Looking into anti-angiogenic gene therapies for disorders of the eye.

Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (DR) are the most common causes of visual impairment in the developed world. Because the key factor in AMD and DR is aberrant neovascularization in the retina (DR) or in the choroid (AMD), strategies to inhibit abnormal neovascularization represent a compelling therapeutic approach. Here we review various anti-angiogenic strategies for the treatment of ocular neovascular diseases with special emphasis on gene transfer as a way of achieving high, sustained concentrations of anti-angiogenic proteins in the back of the eye without concomitant systemic toxicity.