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Muscular dystrophy presents a formidable challenge for gene therapy. Major hurdles include the need to correct large masses of tissue (40% of the body weight) with minimal damage to the already inflamed and necrotic muscles, absence of immune rejection of the therapeutic protein, and sustained (if possible, life-long) expression. Plasmid DNA has long been neglected as a candidate vector for this devastating disease, due to a low in vivo transfection efficiency. It, nevertheless, meets many of the prerequisites for a clinically viable treatment: ease of manufacturing, low toxicity, immunologically innocuous (to allow repeated administrations and insensitivity to pre-existing immunity), and accommodation of the large 11-kb dystrophin cDNA. Over the past year, interest has increased with two major breakthroughs: the first gene-based clinical trial for Duchenne muscular dystrophy that involved a human dystrophin plasmid, and a new method of intravascular delivery showing widespread transfection of limb muscles in large animals, including non-human primates. This opens a new avenue for the treatment of Duchenne dystrophy and many applications using gene delivery to skeletal muscle.

Therapeutic vaccination against cancer-associated antigens represents an attractive option for cancer therapy in view of the comparatively low toxicity and, so far, excellent safety profile of this treatment. Nevertheless, it is now recognized that the vaccination strategies used for prophylactic vaccinations against infectious diseases cannot necessarily be used for therapeutic cancer vaccination. Cancer patients are usually immunosuppressed, and most cancer-associated antigens are self antigens. Therefore, various immunostimulation techniques are under investigation in an effort to bolster immune systems and to overcome immune tolerance to self antigens. Various strategies to stimulate antigen presentation, T-cell reactivity and innate immune activity are under investigation. Similarly, strategies to produce an immunological 'danger signal' at the site of the tumor itself are under evaluation, as it is recognized that while tumor-specific T-cells can be activated at the site of vaccination, they require appropriate signals to be attracted to a tumor. The detection, evaluation and quantification of specific immune responses generated by vaccination with cancer-associated antigens is another important area of therapeutic cancer vaccine evaluation receiving much attention and novel strategies. Multiple clinical trials have been undertaken to evaluate therapeutic vaccines in patients. Aggressive protocols such as those combining specific stimulation of T-cells and chemotherapy or strategies to block immune regulation are having some success.

Coley Pharmaceutical (formerly CpG ImmunoPharmaceuticals) is developing CpG-7909 (ProMune) for use in the potential treatment of cancer and as a vaccine adjuvant. By April 2000, CpG-7909 had entered phase I/II trials for cancer and in March 2002, Coley initiated a phase I trial in non-Hodgkin's lymphoma in combination with rituximab (Rituxan). By October 2002, CpG-7909 was in phase II trials as a vaccine adjuvant. Cpg-7909 is currently also undergoing phase II trials for melanoma.