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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Alemtuzumab, a humanized monoclonal antibody that targets CD52, was recently approved in the EU and Canada for the treatment of patients with active relapsing-remitting multiple sclerosis. Alemtuzumab induces rapid depletion of circulating B- and T-lymphocytes followed by repopulation that leads to a distinctive lymphocyte profile, including an increased proportion of regulatory T-lymphocytes and memory B- and T-lymphocytes. In early open-label studies, alemtuzumab treatment reduced the number of clinical relapses and new MRI lesions in participants with secondary progressive MS. ⋯ Two of these trials showed reduction in risk of confirmed worsening of disability, and all showed reduction in cerebral atrophy. Safety issues include infusion reactions that are mitigated by pretreatment with corticosteroids in addition to symptomatic management with antihistamines; mild to moderate infections; and autoimmune adverse events. In this context, post-marketing risk mitigation strategies will be needed so that potential adverse events can be identified and managed early and effectively.
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Glioblastoma multiforme (GBM) is the most common and aggressive glial cell-derived primary tumor. Current standard of care for patients with GBM includes maximal tumor resection plus adjuvant radiotherapy and temozolomide chemotherapy, increasing median overall survival to a mere 15 months from diagnosis. Because these therapies are inherently nonspecific, there is an increased likelihood of off-target and incomplete effects; therefore, targeted modalities are required for enhanced safety and efficacy. ⋯ Vaccination with rindopepimut has been shown to specifically eliminate cells expressing EGF receptor variant III. Phase II clinical trials have suggested that vaccination of newly diagnosed GBM patients with rindopepimut plus adjuvant granulocyte-macrophage colony-stimulating factor results in prolonged progression-free and overall survival with minimal toxicity. This review will outline the development of rindopepimut, as well as the current status of this vaccine.
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Tumors in about 15% of patients with breast cancer overexpress HER2. Trastuzumab (Herceptin(®); F. Hoffmann-La Roche, Basel, Switzerland) is a humanized monoclonal antibody against HER2. ⋯ The results of a prospective randomized Phase III study have demonstrated that subcutaneous trastuzumab is noninferior compared with the intravenous administration of the drug in terms of efficacy (assessed as pathological complete response rate) as well as in pharmacokinetic parameters. Moreover, another prospective randomized study showed that an overwhelming majority of patients prefer subcutaneous over intravenous trastuzumab. The advent of subcutaneous trastuzumab represents an important progress in the concept of cancer management that is based also on patient choice and preferences.
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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.