Advancing Cancer Therapy with Present and Emerging Immuno-Oncology Approaches

Abstract

Immuno-oncology (I-O) is a young and growing field on the frontier of cancer therapy. Contrary to cancer therapies that directly target malignant cells, I-O therapies stimulate the body’s immune system to target and attack the tumor, which is otherwise invisible to, or inhibiting the immune response. To this end, several methods have been developed: First, passive therapies that enable T-cells to fight the tumor without direct manipulation, typically through binding and modifying the intracellular signaling of surface receptors. Checkpoint inhibitors, perhaps the most well known of I-O therapies; are an example of such. These are monoclonal antibodies that block binding of the tumor cell at receptors that inactivate the T-cell. A variety of small molecules can achieve the same effect by affecting metabolic or signaling pathways to boost the immune response or prevent its attenuation. Drugs originally formulated for unrelated disease states are now being used to treat cancer under the I-O approach. Second, active therapies which often involve direct manipulations that occur in vitro and once introduced to the patient will directly attack the tumor. Adoptive cell transfer is the oldest of these methods. It involves the removal of T-cells from the body, which are then expanded and genetically modified for specificity toward tumor-associated antigens (TAAs), and then reintroduced to the patient. A similar approach is taken with cancer vaccines, where TAAs are identified and reintroduced with adjuvants to stimulate an immune response, sometimes in the context of antigen-presenting cells or viral vectors. Oncolytic viruses are genetically modified natural viruses for selectivity toward tumor cells. The resulting cytotoxicity has the potential to elicit an immune response that furthers tumor cell killing. A final active approach is bi-specific T-cell engagers. These modified antibodies act to link a T-cell and tumor cell through surface receptors and thereby forcibly generate immune recognition. The therapies in each of these subfields are all still very new and ongoing clinical trials could provide even further additions. The full therapeutic potential of the aforementioned therapies, alone or in combination, has yet to be realized, but holds great promise for the future of cancer treatment.

Characterization of cluster of differentiation�47 expression and its potential as a therapeutic target in esophageal squamous cell cancer

“…The effectiveness of immunotherapy has been clinically proven and may therefore be developed as a novel method of treating cancer (8)(9)(10). Treatments that block checkpoint inhibitors, including cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), have been approved by the US Food and Drug Administration to treat melanoma, non-small-cell lung cancer, head and neck cancer, renal cancer and non-Hodgkin's lymphoma (8).…”

“…Treatments that block checkpoint inhibitors, including cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), have been approved by the US Food and Drug Administration to treat melanoma, non-small-cell lung cancer, head and neck cancer, renal cancer and non-Hodgkin's lymphoma (8). Compared with standard therapies, remarkable efficacy has been achieved following the use of checkpoint inhibitors; however, a number of patients with melanoma exhibit no response or resistance to immune checkpoint blockades (11)(12)(13).…”

Immunoinformatic design of multi epitopes peptide-based universal cancer vaccine using matrix metalloproteinase-9 protein as a target

“…Different type of immunotherapy are available including cytokine therapy, checkpoint inhibitors, monoclonal antibodies and therapeutic vaccines. (13, 14) With the latter being the center of many researches in the recent years, cumulating in the approving of Sipuleucel-T By the U.S. Food and Drug Administration (FDA) as the first dendritic cell based therapeutic vaccine for prostate cancer in 2010. (15, 16) vaccine can either be used alone or in combination with other modalities like immune checkpoint inhibitors (ICIs) which shows better results when compared with vaccine monotherapy.…”

Aptamer‐integrated α‐Gal liposomes as bispecific agents to trigger immune response for killing tumor cells

“…With the development of tumor molecular biology and immunology, tumor targeted therapy and immunotherapy have attracted considerable interests in tumor therapy . The tumor targeted therapy has the advantages of excellent specificity, efficacy, and minimal side effects .…”

“…With the development of tumor molecular biology and immunology, tumor targeted therapy and immunotherapy have attracted considerable interests in tumor therapy. [1][2][3] The tumor targeted therapy has the advantages of excellent specificity, efficacy, and minimal side effects. 4,5 By including tumor targeting attribute, immunotherapy with high specificity and efficacy to target tumor cells can be achieved.…”