Boosting the immune response: an alternative combination therapy for cancer patients

Transformation of normal cells into malignant cancer involves a number of changes in the genome. These changes include chromosomal translocations, exon deletions and gene mutations, to name a few, that result in deregulation of the regulatory circuits of the cell and consequently in profound changes in their antigenic composition, including expression of mutated proteins, overexpression of proteins that are produced at much lesser levels in normal tissue and expression of aberrantly glycosylated proteins. It is well established that these new antigenic entities, referred to as tumor-associated antigens (TAA), are recognized by the immune system and elicit immune reactivity. However, the immune reaction is overpowered by the cancer potential to grow and to metastasize. Cancer immunotherapy aims at boosting the naturally occurring immune response at a level that will prevail over the ability of cancer cells to escape immune attack. After more than 20 years of intense research and a growing number of clinical trials, most of which gave marginal results, it is now clear that the task is not an easy one. However, during the same period of time, we have gained a much better understanding of the mechanisms of tumor growth, the mechanisms by which the immune system is activated or becomes tolerant and of the natural relationship between cancers and the immune system. Also, even though few, some immunotherapy strategies have demonstrated positive clinical responses and are already used as standard therapies. These developments give the impetus to explore and devise new strategies that will by more effective in strengthening the immune reactivity at a level that will counteract the tumor potential. In this paper we review the knowledge gained from basic research related to cancer immunity and from clinical trials. We propose that, based on this knowledge, improved clinical protocols can be elaborated.