Many cancers are associated with viral infections, and vaccines that prevent these infections can reduce cancer risk. A major breakthrough in anticancer therapy occurred in 2005 with the completion of a clinical trial involving 12,167 women that tested a vaccine against human papilloma virus (HPV). This trial showed that a recombinant vaccine against HPV was 100% effective in preventing cervical cancer caused by two key HPV strains, HPV-16 and HPV-18, which are associated with 70% of cervical cancers. The vaccine most likely prevents infection of cervical epithelium by HPV through the induction of anti-HPV antibodies (Fig. 16.21). Although this trial showed the potential of vaccines to prevent cancer, attempts to use vaccines to treat existing tumors have been less effective. In the case of HPV, certain types of vaccines that have increased immunogenicity for eliciting T-cell responses are beginning to show effectiveness in treating existing intraepithelial neoplasia caused by the virus. Similarly, the majority of liver cancers are associated with chronic hepatitis caused by several viruses. The vaccine against hepatitis B can reduce primary liver cancer due to this virus, although it will not protect against cancers caused by infections by other viruses such as hepatitis C.
Vaccines based on tumor antigens are, in principle, the ideal approach to T-cell-mediated cancer immunotherapy, but they are difficult to develop. For HPV, the relevant antigens are known. For most spontaneous tumors, however, relevant peptides of tumor rejection antigens may not be the same in different patients’ tumors and may be presented only by particular MHC alleles. This means that an effective tumor vaccine must include a range of tumor antigens. It is also clear that cancer vaccines for therapy should be used only when the tumor burden is low, such as after adequate surgery and chemotherapy.
The sources of antigens for cell-based cancer vaccines are the individual patients’ tumors removed at surgery. These vaccines are prepared by mixing either irradiated tumor cells or tumor extracts with killed bacteria such as Bacille Calmette–Guérin (BCG) or Corynebacterium parvum, which act as adjuvants to enhance the immunogenicity of the tumor antigens (see Appendix I, Section A-41). Vaccination using BCG adjuvants has had variable results in the past, but renewed interest is based on recent appreciation of their interaction with Toll-like receptors (TLRs). Stimulation of TLR-4 by BCG and other ligands has been tested against melanoma and other solid tumors. CpG DNA, which binds to TLR-9, has also been used to increase the immunogenicity of cancer vaccines. In cases where candidate tumor rejection antigens have been identified, for example, in melanomas, experimental vaccination strategies have included the use of whole proteins, peptide vaccines based on sequences recognized by cytotoxic T lymphocytes and helper T lymphocytes (either administered alone or presented by the patient’s own dendritic cells), and recombinant viruses encoding these peptide epitopes.