Rapid complete response of metastatic melanoma in a patient undergoing ipilimumab immunotherapy in the setting of active ulcerative colitis.
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2015
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While blockade of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) T cell regulatory receptor has become a commonly utilized strategy in the management of advanced melanoma, many questions remain regarding the use of this agent in patient populations with autoimmune disease. We present a case involving the treatment of a patient with stage IV melanoma and ulcerative colitis (UC) with anti-CTLA-4 antibody immunotherapy. Upon initial treatment, the patient developed grade III colitis requiring tumor necrosis factor-alpha (TNF-α) blocking antibody therapy, however re-treatment with anti-CTLA-4 antibody following a total colectomy resulted in a rapid complete response accompanied by the development of a tracheobronchitis, a previously described extra-intestinal manifestation of UC. This case contributes to the evolving literature on the use of checkpoint inhibitors in patients also suffering from autoimmune disease, supports future clinical trials investigating the use of these agents in patients with autoimmune diseases, and suggests that an understanding of the specific molecular pathways involved in a patient's autoimmune pathology may provide insight into the development of more effective novel combinatorial immunotherapeutic strategies.
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Bostwick, A Doran, April K Salama and Brent A Hanks (2015). Rapid complete response of metastatic melanoma in a patient undergoing ipilimumab immunotherapy in the setting of active ulcerative colitis. J Immunother Cancer, 3. p. 19. 10.1186/s40425-015-0064-2 Retrieved from https://hdl.handle.net/10161/11661.
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Scholars@Duke
April Kelly Scott Salama
Brent A. Hanks
We are interested in understanding the mechanisms that cancers have evolved to suppress the generation of tumor antigen-specific immune responses and how this knowledge can be exploited for the development of novel and more effective cancer immunotherapy strategies. This work involves the utilization of both autochthonous transgenic tumor model systems as well as clinical specimens to develop novel strategies to enhance the efficacy of immunotherapies while also developing predictive biomarkers to better guide the management of cancer patients with these agents. We strive to translate our understanding of the fundamental biochemical and metabolic pathways within the tumor microenvironment that are critical for driving immune evasion and resistance into early phase clinical trial testing.
Our work utilizes a variety of techniques and methodologies that span the breadth of basic biological research. This work integrates studies based on both 1) transgenic mouse tumor models that are monitored using bioluminescence and micro-CT imaging and 2) a variety of clinical specimens.
Our current areas of focus include:
- Investigating mechanisms of adaptive or acquired immunotherapy resistance in cancer
- Studying the relationship between EMT pathways and immunotherapy resistance.
- Elucidating mechanisms of dendritic cell tolerization in the tumor microenvironment and how these processes may contribute to immunotherapy resistance
- Development of novel pharmacologic and genetic strategies to overcome immunotherapy resistance
- Investigating mechanisms contributing to select immunotherapy-associated toxicities
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