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High frequency of epidemiological threats (H5N1 influenza, SARS, etc.) in modern world calls for the development of new flexible technologies for manufacturing efficacious vaccines and rapid reorientation of their production as appropriate. Genetic vaccination is one of such technologies aimed at prophylaxis of dangerous and socially significant infections. The technology is based on administration of one or several functionally active genes encoding for antigens of pathogens which induces formation of both cellular and humoral immunity against the respective microorganism. This property of genetic vaccines is used for the development of prophylactic schemes. New vaccines are currently being designed to prevent a variety of infections. The aim of the present review is to outline major trends in genetic vaccination leading to the improvement of its efficacy.

Immunotherapeutic strategies to combat neurodegenerative disorders have galvanized the scientific community since the first dramatic successes in mouse models recreating aspects of Alzheimer disease (AD) were reported. However, initial human trials of active amyloid-beta (Abeta) vaccination were halted early because of a serious safety issue: meningoencephalitis in 6% of subjects. Nonetheless, some encouraging preliminary data were obtained, and rapid progress has been made toward developing alternative, possibly safer active and passive immunotherapeutic approaches for several neurodegenerative conditions. Many of these are currently in human trials for AD. Despite these advances, our understanding of the essential mechanisms underlying the effects seen in preclinical models and human subjects is still incomplete. Antibody-induced phagocytosis of pathological protein deposits, direct antibody-mediated disruption of aggregates, neutralization of toxic soluble proteins, a shift in equilibrium toward efflux of specific proteins from the brain, cell-mediated immune responses, and other mechanisms may all play roles depending on the specific immunotherapeutic scenario.

Conventional treatment of hematologic malignancies mainly consists of chemotherapeutic agents or a combination of both, chemotherapy and monoclonal antibodies. Despite recent advances, chemotherapeutic treatments often remain unsatisfying due to severe side effects and incomplete long-term remission. Therefore the evaluation of novel therapeutic options is of great interest. B cell malignancies, in particularly follicular lymphomas, chronic lymphocytic leukemia and multiple myeloma, represent the most immune-responsive types of all human cancer. Several immunotherapeutic strategies are presently employed to combat these B-cell malignancies. Active immunotherapies include vaccination strategies with dendritic cells (DCs) and genetically-modified tumor cell preparations as well as DNA and protein vaccination. Most of these vaccines target the tumor-specific immunoglobulin idiotype and have already demonstrated some anti-lymphoma activity in early phase clinical trials while their definitive impact is evaluated in ongoing phase III randomized trials. In contrast to these active immunizations, T cells transduced with chimeric antigen receptors and donor leukocyte infusions (DLI) represent adoptive (passive) immunotherapies. Recent advances of gene transduction technologies enabled improvement of immunotherapeutic strategies based on genetic modification of malignant cells or adoptive T cells. Current early phase clinical trials are investigating the potential of these innovative approaches. At the moment it remains unclear if the novel immunotherapeutic strategies will be able to play a similar role in the treatment of B cell malignancies than the already established antibody-based immunotherapy.

Immunotherapy is a promising new approach in breast cancer treatment, complementing surgery, chemotherapy, radiation and antihormonal therapy. Primarily, two treatment options are available which are supported by a rapidly growing body of clinical evidence. These are active specific immunotherapy with Theratope and passive immunotherapy targeting the HER-2 receptor with trastuzumab (Herceptin). Trastuzumab has a proven efficacy as monotherapy as well as in combination with chemotherapeutic agents in HER-2-overexpressing metastatic breast cancer. Trastuzumab is generally well tolerated although cardiotoxicity has been observed, especially when in combination with doxorubicin (Adriamycin), where this can be a serious concern. Therefore, less cardiotoxic combinations with docetaxel (Taxotere), vinorelbine (Navelbine) and epirubicin (Pharmorubicin) or cyclophosphamide (Endoxana) have been tested. The combination of trastuzumab with paclitaxel (Taxol) is well approved. The use of trastuzumab in adjuvant and preoperative therapy is currently being examined in controlled trials. After a brief outline of immunotherapy with Theratope and trastuzumab, this article reviews recent and ongoing clinical studies conducted with trastuzumab.

In the past two decades, the worldwide steadily rising incidence of melanoma, its dismal prognosis when locally advanced or metastatic, and the absence of clinically effective therapeutic options have prompted studies that generated extensive preclinical knowledge on the biology of melanoma cells and their interaction with the host's immune system. As a consequence, among solid tumors, melanoma represents a "model malignancy" to design and apply in the clinic new bioimmunotherapeutic approaches, that are eventually translated to solid tumors of different histotypes. Despite its waxing and waning appeal as a therapeutic strategy, antibody treatment still represents a promising clinical approach to melanoma. Europe is no exception in the clinical interest for antibodies as therapeutic tools in melanoma patients; European researchers have also focused on preclinical issues that may improve current antibody-based therapeutic approaches on the one hand, while providing novel clinical strategies on the other hand., (Copyright 2002, Elsevier Science (USA). All rights reserved.)