SPOTLIGHT cancer-targeted immune cells (see Adoptive Cell Therapy, p. 109), or by enhancing T-cell function utilizing proteins known as cytokines (see Enhancing Immune Cell Function, p. 117) or cells that trigger cancer-fighting T cells (e.g., the cancer vaccine sipuleucel-T or Provenge). Other immunotherapeutics work by flagging cancer cells for rapid destruction by the immune system. These include therapeutic antibodies that work by bringing immune cells into close contact with cancer cells and activating them, which leads to cancer cell destruction (422) (see Directing the Immune System to Cancer Cells, p. 120). Yet other immunotherapeutics comprise a virus that preferentially infects and kills cancer cells, releasing molecules that trigger cancer-fighting T cells; these are called oncolytic virotherapeutics, for example, talimogene laherparepvec (T-Vec; Imlygic). Releasing the Brakes on the Immune System Decades of research have revealed that some tumor cells have increased levels of certain proteins on their surface that attach to and activate “brakes” on T cells, thus stopping them from attacking cancer cells. These brakes are proteins on the surface of T cells and are called immune checkpoint proteins. Immune checkpoint inhibitors (ICIs) are a class of transformative new therapeutics that can release the brakes on T cells and trigger T cells to destroy cancer cells (423). Immunotherapeutics Can Work in Many Ways Decades of research and technological advances have allowed researchers to harness the potential of the immune system in treating cancer. In just over a decade, FDA has approved different types of immunotherapeutics that work in multiple ways. These include immunotherapeutics that unleash the natural killing power of the immune system to treat cancer by releasing the brakes on the immune system, such as immune checkpoint inhibitors (A); immunotherapeutics that comprise a virus that preferentially infects and kills cancer cells by releasing molecules that trigger cancerfighting T cells (B); immunotherapeutics that amplify the cancer killing ability of the immune system, such as CAR T-cell therapy (C); immunotherapeutics that enhance the function of the immune system, such as cytokines (D); immunotherapeutics that provide more cancertargeted immune cells to enhance the killing power of the immune system (E); and immunotherapeutics that flag cancer cells for destruction by the immune system, such as therapeutic antibodies. (F). FIGURE 17 A B C D E F Immune checkpoint inhibitors Oncolytic viruses Cancer vaccines Cytokines Adoptive cell therapies Therapeutic antibodies Immunotherapy: Pushing the Frontier of Cancer Medicine AACR Cancer Progress Report 2023 101
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