Targeting the Immune System in Cancer (original) (raw)
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The Immune Response to Tumors as a Tool toward Immunotherapy
Clinical and Developmental Immunology, 2011
Until recently cancer medical therapy was limited to chemotherapy that could not differentiate cancer cells from normal cells. More recently with the remarkable mushroom of immunology, newer tools became available, resulting in the novel possibility to attack cancer with the specificity of the immune system. Herein we will review some of the recent achievement of immunotherapy in such aggressive cancers as melanoma, prostatic cancer, colorectal carcinoma, and hematologic malignancies. Immunotherapy of tumors has developed several techniques: immune cell transfer, vaccines, immunobiological molecules such as monoclonal antibodies that improve the immune responses to tumors. This can be achieved by blocking pathways limiting the immune response, such as CTLA-4 or Tregs. Immunotherapy may also use cytokines especially proinflammatory cytokines to enhance the activity of cytotoxic T cells (CTLs) derived from tumor infiltrating lymphocytes (TILs). The role of newly discovered cytokines r...
Cancer immunotherapy: moving beyond current vaccines
Nature Medicine, 2004
Great progress has been made in the field of tumor immunology in the past decade, but optimism about the clinical application of currently available cancer vaccine approaches is based more on surrogate endpoints than on clinical tumor regression. In our cancer vaccine trials of 440 patients, the objective response rate was low (2.6%), and comparable to the results obtained by others. We consider here results in cancer vaccine trials and highlight alternate strategies that mediate cancer regression in preclinical and clinical models.
A primer on cancer immunology and immunotherapy
Cancer Immunology, Immunotherapy, 2004
The role of immunity in cancer has been abundantly demonstrated in murine tumor models as well as in man. Induction of clinically effective antitumor immune responses, based on this information, in patients with cancer however, remains elusive. This is not because tumors lack recognizable antigens [in fact there is evidence that there are thousands of potential novel targets in each tumor cell] but rather due to the fact that the induction of responses is not adequate nor particularly well understood. Tumors seem to be rather effective at limiting immune responses. Many of the molecularly defined antigens that have been detected on tumor cells are derived from self-proteins and as such are subject to tolerizing mechanisms. Such tumors have also developed escape mechanisms capable of evading or suppressing immune responses. Understanding the role of dendritic cells during the effector phase of the immune response and the complex interactions of stromal, immune, and tumor cells in the tumor microenvironment represent the next challenges to be understood for tumor immunology.
Cancer vaccines and immunotherapy
British medical bulletin, 2002
It is now clear that many human tumour antigens can be recognised by the immune system. These tumour antigens can be classified into several groups including cancer-testis, differentiation, tissue specific, over-expressed, and viral-associated antigens. In many cases, there is a known molecular basis of carcinogenesis which provides the explanation for the differentiated expression of these antigens in tumours compared with normal cells. Improved understanding of the biology of the immune response, particularly of immune recognition and activation of T-cells, allow better design of vaccines. Pre-clinical comparative studies allow evaluation of optimal vaccine strategies which can then be delivered to the clinic. Currently, a range of cancer vaccines are being tested including those using tumour cells, proteins, peptides, viral vectors, DNA or dendritic cells. Ultimately, this research should give rise to an entirely new modality of cancer treatments.
Combating Cancer With Tumor Immunotherapy
e Journal of Biological Sciences, 1 (1), 11-22., 2009
Cancer is a worldwide health problem. Cancer immunotherapy can be studied in two categories: cancer vaccines and induction of immune response against specific antigens. For studying it in a better way to combat cancer, we should look it from the respective angles of immune system's components. For combating cancer, we should look into the roles of innate cells, antibodies, T cells, NK cells, macrophages, and at last the evasion of tumor responses. From all these concepts, we can land on many immunotherapy ways like Humoral or cellular immunotherapy, Passive antibody transfer, APC activity enhancement, and the important role of monoclonal antibodies, Dendritic cells, cytokines and interferons. Still moving further using a pool of these resources, we can combat cancer in a better way.
2019
Although recent therapeutic approaches have revitalized the enthusiasm of the immunological way to combat cancer, still the comprehension of immunity against tumors is largely incomplete. Due to their specific function, CD8+ T cells with cytolytic activity (CTL) have attracted the attention of most investigators because CTL are considered the main effectors against tumor cells. Nevertheless, CTL activity and persistence is largely dependent on the action of CD4+ T helper cells (TH). Thus establishment of tumor-specific TH cell response is key to the optimal response against cancer. CD4+ TH lymphocytes are conventionally primed and activated against antigens, including TAAs, by professional antigen presenting cells (APCs). Priming is mainly induced by dendritic cells (DCs) and less efficiently by macrophages, that present antigens via their cell surface MHC class II molecules.
Aspects of cancer immunotherapy
Immunology and Cell Biology, 2003
Cancer immunotherapy has traditionally undergone a 'revolution' every decade, from the use of Bacille Calmette-Guérin by scarification in the 1970s, to interleukin-2 therapies in the 1980s, and monoclonal antibody treatments in the early 1990s. Usually the early reports on the use of such agents were encouraging, but when more patients were studied in multiple centres, the initial promising results could not be confirmed. Now in a new century, we have more reagents and methods available than ever before -indeed, with such a plethora of reagents it is difficult to envisage them being fully and appropriately tested within the next decade, by which time there will be even more reagents to test. However, there have been three major advances which should lead to substantial progress in cancer immunotherapy: (1) the widespread use of genetic engineering, enabling identification of candidate vaccine proteins and manipulation of their sequences; (2) the production of antigens, antibodies and cytokines in large amounts by recombinant technologies, and (3) an understanding of the mode of presentation of peptides by major histocompatibility complex Class I and Class II molecules and their recognition by T cells. Despite these advances, there are major problems facing cancer immunotherapy, such as the ability of tumours to mutate and evade the immune system and the difficulty of precisely defining the interactions of effector cells in mediating 'rejection' or destruction of a tumour. There are clearly immunological similarities with diseases such as malaria and schistosomiasis, where the invading foreign organisms can use a variety of strategies to resist an elicited immune response. The failure to find a suitable vaccine for these diseases must lead to some pessimism for the development of immunotherapy for an autologous tumour. However, there are promising studies now in progress which should give an indication of the most important directions to follow. This review provides a commentary on aspects of cancer immunotherapy and in particular will deal with: (1) the selection of antigens as vaccine components; (2) the modes of presentation of antigens, particularly by major histocompatibility complex Class I molecules; and (3) new modes of delivery of vaccine immunogens.