Immune therapy for cancer.
ABSTRACT Over the past decade, immune therapy has become a standard treatment for a variety of cancers. Monoclonal antibodies, immune adjuvants, and vaccines against oncogenic viruses are now well-established cancer therapies. Immune modulation is a principal element of supportive care for many high-dose chemotherapy regimens. In addition, immune activation is now appreciated as central to the therapeutic mechanism of bone marrow transplantation for hematologic malignancies. Advances in our understanding of the molecular interactions between tumors and the immune system have led to many novel investigational therapies and continue to inform efforts for devising more potent therapeutics. Novel approaches to immune-based cancer treatment strive to augment antitumor immune responses by expanding tumor-reactive T cells, providing exogenous immune-activating stimuli, and antagonizing regulatory pathways that induce immune tolerance. The future of immune therapy for cancer is likely to combine many of these approaches to generate more effective treatments.
- SourceAvailable from: Daniela Fioretti[show abstract] [hide abstract]
ABSTRACT: A variety of clinical trials for vaccines against cancer have provided evidence that DNA vaccines are well tolerated and have an excellent safety profile. DNA vaccines require much improvement to make them sufficiently effective against cancer in the clinic. Nowadays, it is clear that an increased antigen expression correlates with improved immunogenicity and it is critical to vaccine performance in large animals and humans. Similarly, additional strategies are required to activate effective immunity against poorly immunogenic tumour antigens. This review discusses very recent scientific references focused on the development of sophisticated DNA vaccines against cancer. We report a selection of novel and relevant patents employed to improve their immunogenicity through several strategies such as the use of tissue-specific transcriptional elements, nuclear localisation signalling, codon-optimisation and by targeting antigenic proteins to secretory pathway. Recent patents validating portions or splice variants of tumour antigens as candidates for cancer DNA vaccines with improved specificity, such as mesothelin and hTERT, are also discussed. astly, we review novel patents on the use of genetic immunomodulators, such as “universal” T helper epitopes derived from tetanus toxin, E. coli heat labile enterotoxin and vegetable proteins, as well as cytokines, chemokines or costimulatory molecules such as IL-6, IL-15, IL-21 to amplify immunity against cancerRecent Patents on Anti-Cancer Drug Discovery 01/2014; 9(1):66-82. · 2.70 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: FOXP3(+)CD25(+)CD4(+) regulatory T (Treg) cells, crucial for the maintenance of immunological self-tolerance, are abundant in tumors. Most of them are chemo-attracted to tumor tissues, expanding locally and differentiating into a Treg-cell subpopulation that strongly suppresses the activation and expansion of tumor-antigen-specific effector T cells. Several cancer immunotherapies targeting FOXP3(+)CD4(+) Treg cells, including depletion of Treg cells, are currently being tested in the clinic. In addition, clinical benefit of immune-checkpoint blockade, such as anti-CTLA-4 monoclonal antibody therapy, could be attributed at least in part to depletion of FOXP3(+)CD4(+) Treg cells from tumor tissues. Thus, optimal strategies need to be established for reducing Treg cells or attenuating their suppressive activity in tumor tissues, together with activating and expanding tumor-specific effector T cells.Current opinion in immunology 01/2014; 27C:1-7. · 10.88 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Cancer immunotherapy holds great promise, yet its efficacy and applicability can be hampered by the rise of systemic toxicities. We have recently shown that the lethal side effects of cancer immunotherapy are markedly exacerbated with aging. Blocking tumor necrosis factor α or macrophages can alleviate the systemic toxicity of immunotherapy while preserving its antineoplastic effects.Oncoimmunology. 12/2013; 2(12):e27186.