The cancer journal
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Most patients with head and neck squamous cell cancer (HNSCC) will present with advanced disease characterized by poor prognosis and limited treatment options. Our growing understanding of the complex crosstalk between tumor cells and the immune system has facilitated the development of promising therapies targeting immune checkpoints, such as programmed death 1 and the cytotoxic T-lymphocyte antigen 4, which are producing considerable clinical responses. ⋯ This may be counteracted by optimizing the dosing, sequence, and timing of immune checkpoint therapies and by combining these regimens with other modalities such as radiation therapy, cancer vaccines, cytotoxic chemotherapies, and molecularly targeted agents. The present review summarizes the pathophysiological role of immune regulation in HNSCC and provides a concise update on the clinical translation of immune checkpoint therapies in this tumor type.
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Renal cell carcinoma (RCC) is a largely chemotherapy-resistant disease that is commonly treated with molecularly targeted therapies. Evidence suggests that RCC is also an immune-responsive disease, and checkpoint inhibitors are in active development as agents for the treatment of systemic disease. ⋯ Nivolumab is the most completely characterized anti-PD-1 agent in RCC and has been shown to be efficacious as monotherapy. Currently, there are multiple ongoing clinical trials exploring the use of combination therapy with PD-1 blockade.
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Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by a reactive immune infiltrate surrounding relatively few malignant cells. In this scenario, active immune evasion seems to play a central role in allowing tumor progression. Immune checkpoint inhibitor pathways are normal mechanisms of T-cell regulation that suppress immune effector function following an antigenic challenge. ⋯ In this review, we discuss the rationale for targeting PD-1 and PD-L1 in the treatment of HL. We will evaluate the published clinical data on the different agents and highlight the safety profile of this class of agents. We discuss the available evidence on the use of biomarkers as predictors of response to checkpoint blockade and summarize the areas under active investigation in the use of PD-1/PD-L1 inhibitors for the treatment of HL.
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The expression of CD30 receptors is one of the defining characteristics of the malignant Reed-Sternberg cells of Hodgkin lymphoma (HL). CD30 is rarely expressed by normal cells and is rapidly internalized, making it an ideal therapeutic target for monoclonal antibodies and for antibody-drug conjugates. Brentuximab vedotin is the first antibody-drug conjugate to be approved by regulatory agencies for the treatment of patients with relapsed HL, with a single-agent response rate of 75%. In this review article, we discuss the current and ongoing development of brentuximab vedotin in patients with relapsed and newly diagnosed HL.
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Relapsed and refractory hematologic malignancies have a very poor prognosis. Chimeric antigen receptor T cells are emerging as a powerful therapy in this setting. Early clinical trials of genetically modified T cells for the treatment of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia have shown high complete response rates in patients with few therapeutic options. ⋯ At the same time, the design and production of chimeric antigen receptor T cells are being advanced so that this therapy can be more widely utilized. Cytokine release syndrome and neurotoxicity are common, but they are treatable and fully reversible. This review will review available data as well as future developments and challenges in the field.