Future developments in cancer vaccinology have to take the above-discussed experiences into account. While there is ample room for improvements in vaccine designs and delivery schemes, the basic problem of immune evasion by antigen loss cannot be overcome by vaccination therapy. It needs to be defined, therefore, for which cancers, in which disease states, and possibly in which schemes of combination therapy therapeutic vaccination can best exert its potential against cancer.
Nearly all clinical trials for therapeutic cancer vaccine have been conducted with advanced-stage patients. These conditions are expected to be the most difficult to treat, and cure by therapeutic vaccination is bound to remain the exception. However, the extended survival of patients under vaccination therapy suggests its suitability for maintenance therapy where cure is not possible. Adjuvant therapy after surgery may be an important indication for tumor vaccination. A very extensive study with colon carcinoma patients who received vaccines after surgical resection of the tumors demonstrates a clear benefit for the vaccinated patients and lends strong support to the above notion.
Early stage cancers could be much more responsive to therapeutic vaccination. However, this option has not yet been tested in greater detail, and further conclusions have to await the outcomes of thorough clinical vaccination trials with early-stage cancer patients. Prophylactic vaccinations would be ideal and are in fact promising prospects for cancers with a microbial etiology. Vaccination against human papilloma viruses is currently being tested for prevention of cervical carcinoma. Although it will take many more years before the efficacy of such prophylaxis can be assessed properly, the initial investigations indicate a substantial reduction of pre-cancerous conditions after vaccination.
For most cancers, prophylaxis is not possible and for most patients therapeutic vaccination is not a dependable option. Immune evasion by antigen loss or suppression too often quenches the antitumor effects of the vaccination. Therapy resistance, such as by antigen loss, is not restricted to immunotherapy; it is the key problem for clinical oncology in general. Given the genetic instability and heterogeneity of tumor cells as the likely basis for the selection of therapy-resistant tumor variants, future developments in oncology need to devise treatment regiments that can cope with the diversity of the tumor cells. Such new therapies could be combinations of different therapeutic principles that target the tumor cells at different pathogenically relevant sites. Therapeutic vaccination could be an important component of such combination therapies.
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