The goal of immunotherapy in cancer is to elicit an immune response against tumor antigens to a level that is sufficient to control and eliminate malignant growth. It has been known that a weak, but ineffective anti-tumor response can often be detected in tumor-bearing hosts including cancer patients. The ineffectiveness of this immune response reflects an imbalance between the immune system and the malignant growth. To achieve a meaningful anti-tumor response, the transfer of a large number of tumor-reactive T-cells could lead to the regression of existing tumors in both animals and man. This approach has been termed "adoptive immunotherapy." By contrast, active immunotherapy aims to illicit or boost immune responses in tumor-bearing hosts through vaccination. Although theoretically attractive, current vaccine approaches have generally been unsuccessful. Both the tumor’s weak antigens and the lack of effective antigen presentation of these antigens have attributed to the difficulties associated with effective design of cancer vaccines.

 

Over the past decades, dendritic cells (DCs) have been identified to be the most potent antigent presenting cells (APCs). The ability to generate large number of DCs in vitro has fueled enthusiasm in using DCs as a tool for antigen delivery. To induce immune responses to tumor, DCs have been loaded with soluble tumor peptides, proteins, cell lysates, as well as transfection with tumor RNA, to name just a few. Traditionally, however, whole tumor cells, inactivated by radiation or mitomycin-C treatment, have been the best antigens for immunization. To preserve tumor cell viability and DC functionality, we have recently generated DC-tumor heterokaryons by an electrofusion procedure. The greatest advantage of a fusion vaccine is that it could present known and undefined antigens to both MHC I and II pathways. In at least five antigenically distinct murine tumors in three different inbred mice, we have demonstrated that a single fusion vaccination was capable of mediating the regression of tumor established in various visceral organs.

 

In animals studies, the strongest therapeutic immunity has always been illicited against the elusive tumor specific tumor antigens (TSTA), which are rarely genetically cloned and chemically defined because the are expressed uniquely on individual tumors. By contrast, the more recently identified human TAAs are either derived from mutated or over-expressed cell proteins or cryptic epitopes of differential proteins that are shared among tumors of the same and different histologies. This group of shared antigens is a potential target for the development of immunotherapy in humans. Although the use of autologous (syngeneic) tumors is ideal for immunotherapy, the difficulties of establishing tumor cell lines in vitro in most cancer patients prohibits its application in the clinic. A clinically amiable approach will be the use of well-established allogeneic tumor cell lines, which express shared TAAs. In this approach, one must consider both the positive and negative consequences of an immune response against histocompatiblity antigens. If successful, however, immunotherapy should be routinely available for most cancer patients.