Gene-modified cellular vaccines: technologic aspects and clinical problems.

Activity in the cancer vaccine sector has quadrupled in the last decade. A number of therapeutic cancer vaccines are reaching the market. The huge number of clinical trials in progress is expected to undergo evaluation shortly. Whole cell tumor vaccines or gene-modified whole cells are being intensively tested in clinical trials. However, the specificity of the product makes the drug development process, including clinical trials, a considerable challenge. Their complex nature, standardization of manufacturing, and characterization often pose problems. Accordingly, to develop a well characterized controlled vaccine, more than a few factors need to be established. The final cell vaccine formulation must be characterized for product identity, purity, impurities, sterility, potency, cell viability, and total cell number. Therapeutic cancer vaccines show different clinical characteristics than cytotoxic anticancer agents. Unfortunately, the rules of clinical trial design for active immunotherapy have been adapted from the designs for examination of cancer chemotherapy. Accordingly, many research groups and clinical consortia have postulated modifications and unifications of existing clinical trial designs. A clinical development model has suggested that cancer vaccines be investigated in 2 categories of clinical trials: proof-of- principle and efficacy. Moreover, it is becoming clear that no drug demonstrates anticancer activity in all patients. Thus, intensive studies have been performed to seek specific biomarkers which could help stratify patients who are likely to respond to a particular treatment. This presents a big challenge beyond the analysis of the immune system status necessary to assess the effects of active immunotherapy.