SPOTLIGHT Enhancing Immune Cell Function Immune cells communicate with each other and with their surrounding cells by direct contact as well as through the release of a class of molecules called cytokines. Cytokines are also produced by nonimmune cells and play an essential role in rapidly activating the immune system in response to cellular stresses, such as infection, inflammation, and cancer (457). For many decades, researchers have been investigating the natural cancer killing ability of two cytokines, interferon-alpha (IFNα) and interleukin-2 (IL-2), to boost the cancer-killing function of the immune system (458). Discoveries in the late 1960s established the role of interferons in suppressing tumor growth, which led to subsequent clinical trials confirming their anticancer effects (449). In 1986, IFNα became the first FDA-approved cancer immunotherapy when it was approved for the treatment of a rare blood cancer known as hairy-cell leukemia (459). Although cytokines have shown some promise as immunotherapeutics, their success has been limited. One limitation is that cytokines do not persist very long in the body, so ongoing research is developing more stable versions of cytokines (461). Another challenge is the significant adverse effects when cytokines are administered as a systemic treatment. Researchers are exploring ways to enhance the efficacy of interferons while minimizing their side effects, for example, by delivering them in or near tumors (461). The FDA approval of nadofaragene firadenovec-vncg (Adstiladrin) in December 2022, was a major advance in the field of interferonbased cancer immunotherapy. The FDA approved nadofaragene firadenovec-vncg for the treatment of adult patients with highrisk, non–muscle-invasive bladder cancer (NMIBC) that did not respond to Bacillus Calmette-Guérin (BCG) treatment. More than 82,000 new cases of bladder cancer will be diagnosed in the United States in 2023 (28). Non–muscle-invasive bladder cancer—a type of cancer that has grown through the lining of the bladder but hasn’t yet invaded the muscle layer—makes up around 75 percent of all new cases of bladder cancer (462). Patients with high-risk NMIBC are usually treated with BCG—an immunotherapeutic that was originally developed as a vaccine against tuberculosis (TB)—which is instilled directly into the bladder. While 80 percent of patients initially respond to BCG, within a year over half of patients with an initial response experience recurrence and progression of cancer, and many develop disease that becomes BCG-unresponsive (463,464). CAR T-cell Therapies Approved by the U.S. Food and Drug Administration As of July 31, 2023, there are six distinct FDA-approved CAR T-cell therapies to treat different cancer types: APPROVAL YEAR THERAPY NAME TREATMENT FOR 2022 Ciltacabtagene autoleucel (Carvykti) Adult patients with relapsed or refractory multiple myeloma 2021 Idecabtagene vicleucel (Abecma) Adult patients with relapsed or refractory multiple myeloma 2021 Lisocabtagene maraleucel (Breyanzi) Adult patients with certain types of B-cell lymphoma 2020 Brexucabtagene autoleucel* (Tecartus) Patients with relapsed or refractory mantle cell lymphoma 2017 Tisagenlecleucel* (Kymriah) Adult patients with certain types of B-cell lymphoma and young adult patients up to age 25 with certain types of lymphoblastic leukemia 2017 Axicabtagene ciloleucel* (Yescarta) Adult patients with certain types of B-cell lymphoma *These therapeutics have received expanded approvals for the treatment of additional blood cancer types since their first approvals by FDA. SIDEBAR 40 continued on page 120 Immunotherapy: Pushing the Frontier of Cancer Medicine AACR Cancer Progress Report 2023 117
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