Researchers have compared paracrine GM-CSF (either by transduction or by time-release microspheres) with BCG and C. parvum in seven or eight different tumor models. The resulting systemic immune response generated by GM-CSF is between 1.5 and 4.0 logs more potent than either adjuvant.
While researchers have learned a tremendous amount from their experiments, they are also certain that transducing autologous tumor explants is not feasible for large-scale application in the general patient population. Microsphere approaches obviate the need for GM-CSF transduction, and the question is moot if immunodominant tumor antigens are in fact shared.
However, it may be 15 to 30 years before investigators identify the relevant antigens for all of the important tumors.
GM-CSF significantly up-regulates both Th-1 and Th-2 lymphokines.
A single vaccination with B7-transduced tumor cells does not evoke a measurable response that maps to the tumor’s MHC type. There is a small response to a second vaccination.
Tumor antigens will ultimately prove to be very important, but at present the best strategy for identifying immunorelevant antigens is to use whole-cell vaccines and let the immune system indicate which of the 50,000 or 100,000 antigens in that tumor it is capable of responding to.
There is no data to support the assertion that viral sequences bind to MHC better than self-sequences. However, high-affinity binding generates a much more profound tolerance.
A total of 10 percent or 15 percent of tumors turn off MHC Class I, in which case CTL response is irrelevant. In such cases, NK cells can be brought into the response to replace CD8 responses.
Once the relevant antigens are defined, melanoma and cervical cancer are both logical targets for cancer vaccines. So, too, are cancers of dispensable tissues (e.g., ovary, prostate, breast). Eventually, tumor vaccines might be used prophylactically, to prevent tumors caused by viruses before they occur (e.g., human papilloma virus, hepatitis C virus).