SPOTLIGHT Patients who do not respond to BCG have very few treatment options other than surgical removal of the bladder. Although potentially curative, such surgical therapy is associated with high rates of complication. Additionally, many patients with underlying health conditions are unwilling or unable to undergo the surgery (464). Therefore, alternative treatments for patients with bladder cancer, such as Lesa Kirkman, p. 118, are an urgent medical need, and are addressed by the nadofaragene firadenovec-vncg approval. Nadofaragene firadenovec-vncg is a novel therapeutic. It is the first gene therapy approved for bladder cancer. When instilled into the bladder through a urinary catheter, the therapeutic infiltrates the bladder cells and delivers a gene encoding interferon alpha 2b (IFNα2b) into the DNA of the cells it infiltrates. Once the gene is incorporated into the bladder cells, they produce the IFNα2b protein, which blocks bladder cancer growth through the activation of immune cells, among other mechanisms (466). The approval was based on a Phase II, single arm study with registration intent. Findings of the study showed that among 51 percent of patients treated with nadofaragene firadenovec-vncg no cancer cells could be detected in their urine and in the urinary bladder tissue (464). Researchers are also evaluating IFNα2b treatment as a potential therapy for other cancer types. As one example, recent data show that people with low-grade lymphomatoid granulomatosis, a rare condition that can progress into an aggressive B-cell lymphoma, can live for decades after diagnosis when treated with IFNα2b (467). This is a remarkable advance compared to findings from past studies showing median survival of less than two years for people with lymphomatoid granulomatosis. Directing the Immune System to Cancer Cells An immune cell must find a cancer cell before it can attack and eliminate it. Many therapeutic antibodies approved by FDA for the treatment of various types of cancer work, at least in part, by helping immune cells find cancer cells. Because of the effectiveness and promise of antibody-based immunotherapeutics, many researchers have been working to develop new as well as improved versions of this important class of anticancer therapeutics. One class of recently developed therapeutic antibodies is known as T-cell engaging bispecific antibodies. Using two or more arms that are engineered into these antibody particles, these immunotherapeutics bind to immune cells and cancer cells simultaneously. By acting as a connector, T-cell engaging bispecific antibodies bring cancer cells into close proximity with T cells, which are then activated and eliminate the cancer cells. The first of these agents, blinatumomab (Blincyto), was approved by FDA in December 2014 for treating certain patients with a type of acute lymphoblastic leukemia (ALL) called B-cell ALL (468). Unprecedented advances in genetic engineering, molecular biology, and immunology over the past decade have led to a rapid proliferation in this innovative new area of cancer medicine. Between August 1, 2022, and July 31, 2023, FDA approved four new T-cell engaging bispecific antibodies for the treatment of a number of hematologic cancers. In October 2022, FDA approved teclistamab-cqyv (Tecvayli) for adult patients with multiple myeloma that has relapsed after, or never responded to, at least four prior lines of therapy. Teclistamab-cqyv attaches to a molecule called CD3 on T cells with one arm and to B-cell maturation antigen (BCMA), BCG IMMUNOTHERAPY AGAINST CANCER Currently BCG immunotherapy remains a standard of care for high-risk non–muscle-invasive bladder cancer. BCG, Bacillus Calmette–Guérin. Developed from (465). Therapeutic antibodies are proteins that are effective in the treatment of numerous cancer types and function in several different ways by attaching to a specific molecule in the body. 1908 Work on BCG vaccine, a less pathogenic mycobacterium strain, begins 1921 BCG vaccine is developed 1882 Discovery of Mycobacterium tuberculosis as the causative organism of TB 1950 Anticancer eect of BCG is observed in mice 1929 Cancer incidence is observed to be significantly lower in TB patients 1976 Ecacy of BCG in treating patients with bladder cancer is first reported 1990 FDA approves the use of BCG vaccine for early-stage bladder cancer AACR Cancer Progress Report 2023 Immunotherapy: Pushing the Frontier of Cancer Medicine 120
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