Tumor cell vaccines can be generated from either the patients' own tissues (autologous) or other sources (allogeneic). An
autologous tumor cell-based vaccine against melanoma, conjugated to a hapten (dinitrophenyl), demonstrated improved disease-free
and overall survival as compared to historical controls.28 It is currently undergoing Phase 1 and 2 clinical studies. Canvaxin has been one of the most promising allogeneic melanoma
vaccines investigated to date. It is an irradiated whole-cell vaccine derived from three different melanoma cell lines, and
administered with BCG as adjuvant. These cell lines were screened to ensure the greatest likelihood that the vaccine would
contain an antigen common to each recipient's tumor. Canvaxin was shown to express at least 20 distinct melanoma associated
antigens, immune responses to which have been associated with survival in vaccine recipients.29
Dendritic cell based vaccines are under active development. Once dendritic cells are generated, they can be loaded with tumor
antigens through the addition of tumor antigens to the culture media, through incubation with autologous or allogeneic tumor
lysate, through gene modification with tumor antigen cDNA or autologous tumor mRNA, or through creation of tumor cell–dendritic
cell hybrids. Provenge, a vaccine against prostate cancer developed by Dendreon, is prepared from a patient's own monocytes
and then loaded with a tumor antigen (a fusion protein of full-length PAP and GM-CSF). In hormone-refractory prostate cancer
patients treated with the vaccine, the median survival was significant longer than placebo.30
Plasmid DNA and viral vector based vaccines have been actively tested in clinical trials. Intramuscular or intradermal plasmid
DNA administration is attractive because gene-transduction of the recipient's cells will result in continuous production of
the tumor antigen. Recombinant viral vectors are commonly used to enhance gene transduction efficiency over plasmid DNA. A
significant challenge of this strategy is the presence of pretreatment antiviral antibodies, which can neutralize the effects
of subsequent treatment.
Preventive cancer vaccines are mostly in the early research stage. New breakthroughs will depend on an increased understanding
of what tumor-specific antigens are expressed during the initial tumor development stage.
Malaria infection occurs in more than 30% of the world's population, almost exclusively in developing countries, and results
in one million deaths annually. Most cases of the disease in humans are caused by four different species of the malarial parasite.
There is currently no vaccine available for the parasite pathogens that infect humans, despite extensive efforts. The complex
lifecycle of the malaria parasite contributes to the complexity of developing an effective vaccine. The parasite is spread
by insect vectors that go through different stages and forms (intracellular, extracellular, sexual, and asexual) as they grow
in the blood and tissues (primarily the liver) of the human hosts. Malaria is difficult to grow in large quantities outside
the natural host.3
Malaria vaccine development has been focused on subunit vaccines targeting either the pre-erythrocytic or erythrocytic stage
of the parasite lifecycle.31 The vaccine that is currently most advanced in development is the RTS,S vaccine in an AS02 adjuvant. It comprises portions
of the circumsporozoite protein (CSP) linked to components of the hepatitis B surface antigen such that immunogenic particles
are formed. The vaccine (given three doses over several months) provided protection in 41% of the individuals in sporozoite
challenge studies. Subsequent field trials showed significant protection in adults and recently in children. This vaccine
is believed to act mainly through antisporozoite antibodies, but perhaps also through T-cells that target infected hepatocytes.