Klin Onkol 2005; 18(4): 126-133.
Summary: The ultimate goal of tumour immunotherapy is to modulate a patient’s immune system in the course of cancer disease to the extent of being able to eliminate or at least reduce the tumour load. The active immunotherapy tries to achieve this goal by active immunization, i.e. therapeutic vaccination. Its underlying principle is a specific activation of the patient’s immune system by a convenient delivery of tumour antigens of choice, which can adopt a variety of forms (lethally irradiated cancer cells, tumour lysates, antigenic proteins or peptides, peptide-loaded dendritic cells etc.). Actual efficacy of these approaches, in terms of an objective clinical response, is quite low (3 – 10 %). Two prominent directions are appearing in the current development of the active immunotherapy of cancer. The first is an effort to understand the factors determining the clinical response on a level of basic immunological and molecular biological knowledge, e.g. in terms of differentially expressed genes or polymorphic information in the genome itself. Important goal of this approach is to predict with reasonable accuracy the clinical response of a tumour before starting the vaccination. The second direction of the current development in this field is a search for new tumour antigens or vaccination protocols with improved clinical efficacy. Telomerase seems to be such a promising new antigen and, likewise, application of vaccines based on complexes of peptides with heat shock proteins is similarly regarded with hope. Their clinical impact awaits, nevertheless, validation in larger clinical studies. The second main approach to the tumour immunotherapy, namely the passive immunotherapy, consists in supplementing the patient’s immune system with ex vivo prepared and activated immune effectors. Traditionally represented by antibody-based therapies, passive immunotherapy approaches scored recently important clinical successes for cell-based therapies as well, namely in exploiting natural killer cell activation in frames of allogeneic and haploidentical blood stem cell transplantation in treatment of some leukaemias, and in adoptively transferred short-term in vitro expanded autologous tumour infiltrating lymphocytes in treatment of metastasizing malignant melanoma. A new development in passive cellular immunotherapy is an effort to manipulate the T cell receptor genes to increase their affinity for a tumour antigen in question. A little removed from these two main immunotherapeutic branches is tumour treatment based on sole cytokine administration, with the two major cytokines being interleukin-2 and interferons-<. Molecular analysis of genes activated and repressed by IFN< treatment of malignant melanoma suggests that this treatment might result in suppression of some melanocyte-specific immunodominant antigens, which could be exploited with advantage in terms of successive therapeutic vaccination.
