Cancer Immunotherapy Comes of Age

Abstract

Cancer immunotherapy comprises a variety of treatment approaches, incorporating the tremendous specificity of the adaptive immune system (T cells and antibodies) as well as the diverse and potent cytotoxic weaponry of both adaptive and innate immunity. Immunotherapy strategies include antitumor monoclonal antibodies, cancer vaccines, adoptive transfer of ex vivo activated T and natural killer cells, and administration of antibodies or recombinant proteins that either costimulate immune cells or block immune inhibitory pathways (so-called immune checkpoints). Although clear clinical efficacy has been demonstrated with antitumor antibodies since the late 1990s, other immunotherapies had not been shown to be effective until recently, when a spate of successes established the broad potential of this therapeutic modality. These successes are based on fundamental scientific advances demonstrating the toleragenic nature of cancer and the pivotal role of the tumor immune microenvironment in suppressing antitumor immunity. New therapies based on a sophisticated knowledge of immune-suppressive cells, soluble factors, and signaling pathways are designed to break tolerance and reactivate antitumor immunity to induce potent, long-lasting responses. Preclinical models indicate the importance of a complex integrated immune response in eliminating established tumors and validate the exploration of combinatorial treatment regimens, which are anticipated to be far more effective than monotherapies. Unlike conventional cancer therapies, most immunotherapies are active and dynamic, capable of inducing immune memory to propagate a successful rebalancing of the equilibrium between tumor and host.

The Applications and Prospects of Blockade of Programmed Death—1 Antibody in the Process of Treating Colorectal Cancer

“…Although an endogenous immune response to cancer is observed in preclinical models and patients, this response is ineffective, because tumors develop multiple resistance mechanisms, including local immune suppression, induction of tolerance, and systemic dysfunction in T-cell signaling [17][18][19][20]. Moreover, tumors may exploit several distinct pathways to actively evade immune destruction, including endogenous "immune checkpoints" that normally terminate immune responses after antigen activation or both [21].…”

Cancer Immunotherapy and Immunonutrition

“…ACT would hopefully circumvent the tolerance to tumor antigens and produces high avidity in effector T-cells, but is only currently restricted to melanoma, and has safety issues and serious adverse effects and lacks of long lasting responses. It is also an expensive treatment and requires time to develop the desired cell population [7][8][9].…”

Immunotherapy in ovarian cancer

“…Immunotherapy has found particular success in the treatment of other immunogenic cancers, in particular melanoma and renal cell carcinoma, 14 and successful strategies are being extrapolated into the treatment of ovarian cancer. Traditionally, immunotherapeutic strategies have focused on enhancing, inducing or suppressing innate or adaptive immune responses.…”

“…15 In addition, more recent approaches have investigated immunomodulatory strategies aimed at removing immune inhibitory responses due to Tregs and CTLA-4. 14,15 ( Table 1) Cytokine therapy. Anti-tumor immune responses have been generated in preclinical models with the administration of cytokines, including IL-2, -4, -7, -12 and -18, IFN-α, IFN-γ, tumor NY-ESO-1 is a cancer-testis antigen which is highly immunogenic and has high expression in ovarian cancer.…”