Immunotherapy
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Randomized Controlled Trial Multicenter Study
Vedolizumab for ulcerative colitis and Crohn's disease: results and implications of GEMINI studies.
Vedolizumab (VDZ) is a selective antibody against α4β7-integrin, which targets leukocyte trafficking in the gastrointestinal tract. The GEMINI studies are Phase 3, randomized, placebo-controlled trials to assess the efficacy of VDZ in induction and maintenance of moderately to severely active ulcerative colitis (GEMINI 1) and Crohn's disease (GEMINI 2). Included in these studies are patients who have failed TNF-α antagonist therapy. ⋯ GEMINI 2 met one of two primary end points in the induction phase showing that VDZ is more likely to induce clinical remission compared with placebo. VDZ is an effective agent in the maintenance of Crohn's disease. These studies pave the way to a new class of medications for treatment of inflammatory bowel disease.
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Peptides and peptidomimetics can function as immunomodulating agents by either blocking the immune response or stimulating the immune response to generate tolerance. Knowledge of B- or T-cell epitopes along with conformational constraints is important in the design of peptide-based immunomodulating agents. ⋯ The design of peptides/peptidomimetics for immunomodulation in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, systemic lupus and HIV infection is reviewed. In cancer therapy, peptide epitopes are used in such a way that the body is trained to recognize and fight the cancer cells locally as well as systemically.
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In the final issue of Science in 2013, the American Association of Science recognized progress in the field of cancer immunotherapy as the 'Breakthrough of the Year.' The achievements were actually twofold, owing to the early success of genetically engineered chimeric antigen receptors (CAR) and to the mounting clinical triumphs achieved with checkpoint blockade antibodies. While fundamentally very different, the common thread of these independent strategies is the ability to prevent or overcome mechanisms of CD8(+) T-cell tolerance for improved tumor immunity. Here we discuss how circumventing T-cell tolerance has provided experimental insights that have guided the field of clinical cancer immunotherapy to a place where real breakthroughs can finally be claimed.
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Recent research has provided strong support for the utility of broadly neutralizing antibodies generated against viruses, which inherently possess a high degree of antigenic variability (such as influenza virus or HIV) as a feasible means to prevent infection. Many of these antibodies share the ability to bind to highly conserved regions within the stem of the virus 'spike' or surface glycoprotein, in such a way that they interfere with virus entry, including membrane fusion. As a result, broadly neutralizing antibodies could be supplied to patients as a form of passive immunotherapy, as well as play a role in the design of new 'universal' vaccines and antiviral agents. The following article describes the most recent innovations in this exciting field.
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Evaluation of: Younes A, Connors JM, Park SI et al. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a Phase 1, open-label, dose-escalation study. Lancet Oncol. 14(13), 1348-1356 (2013). ⋯ Now in Phase I clinical trial, it has been shown that combining BV with multiagent chemotherapy (excluding bleomycin) as first-line treatment in HL patients with high-risk disease is feasible. Complete response rates were over 90% and toxicity was manageable. Given that the malignant cell population comprises a minority of HL lesions, and that BV releases a diffusible cytotoxin via a cathepsin B-cleavable linker, we argue that a significant proportion of the antitumor activity of BV can be attributed to bystander cytotoxicity in addition to direct killing of CD30-expressing malignant cells.