Cancer Immunotherapy: Perspectives and Prospects

During the last 15–20 years, immunotherapy has emerged as an alternative or adjuvant approach to cancer treatment. The immunotherapy of cancer holds promise in harnessing the host immune response to specifically target tumor cells. Although the potential of this strategy remains auspicious, the approach requires optimization. In this review, we intend to delineate basic aspects of the different immunotherapeutic modalities, their advantages and drawbacks, as well as ways to improve the efficacy of each, either alone or in combination with others.

A key advance in immunology in the past decade has been the elucidation of the antigenic basis of tumor-cell recognition and destruction. As in normal cells, tumor cells express MHC-peptide antigen complexes, and thus can elicit specific HLArestricted immune responses. The result of such responses is the generation of specific CD4⁺ and CD8⁺ T lymphocytes, as well as antibodies, against peptide epitopes derived from tumor-associated antigens (TAA). TAA fall into four categories: unique antigens (mutated, alternatively processed, idiotypic antibodies), shared antigens (cancer/testis antigens, normally expressed during development but aberrantly expressed in adult somatic cells, i.e., NY-ESO-1), differentiation antigens (celllineage- specific, i.e., Melan-A/MART-1, gp100), overexpressed antigens (expressed at higher levels than in normal cells, i.e., HER-2/neu), and viral antigens (HPV, HBV, EBV, etc.) (72).