ABSTRACT
The concept that tumor growth could be susceptible to control by the host's immune system dates to the early 1900s. However, it was not until 1957 that Prehn and Main convincingly demonstrated that active specific immunization could induce a functionally effective antitumor immune response. These investigators immunized syngeneic mice with a chemically induced sarcoma using a technique whereby the transplanted tumor was allowed to grow but was excised before it killed the host. These now surgically cured mice were able to reject a subsequent transplant of the same tumor yet accept a skin graft from a mouse of the same strain as that in which the tumor had arisen. This experiment provided a scientific foundation for the pursuit of active specific immunization as a cancer treatment (i.e., antigens existed on tumor cells which could be targeted to effect tumor rejection). Early trials of active specific tumor immunotherapy, both in animals and in man, utilized whole tumor cells as a source of immunogen. Clinical trials focused mainly on melanoma and to a lesser extent renal cell, colon and lung cancers. It is encouraging that active specific immunization with tumor cell-based vaccines, when optimally formulated, induced objective tumor 312regression in 10-20% of patients (reviewed by Mastrangelo et al., 1995a). However, the limited availability of relevant tumor cells, and the cumbersome processing required, curtailed the application of such vaccines. In the search for a more user friendly vaccine, most investigators are exploring chemically defined tumor associated antigens. We continue to focus on autologous tumor cells because these cells display not one but all of the potential antigens, both known and as yet unidentified, expressed by the patient's tumor. Our goals are to facilitate the exploitation of autologous tumor cells as an antigen source and to improve their immunogenicity by manipulation in situ in vivo.
