Expert opinion on biological therapy
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Expert Opin Biol Ther · Aug 2016
ReviewImmune checkpoint inhibitors in gynecologic cancers with lessons learned from non-gynecologic cancers.
The immune system plays a critical role in controlling cancer through a dynamic relationship with cancer cells. Immunotherapy can establish a sustained immune response against recurring cancer cells leading to long-term remissions for cancer patients. The use of immune checkpoint inhibitors, which work by targeting molecules that regulate immune responses, might be a promising avenue of immunotherapeutic research in gynecologic cancers. ⋯ After years of very little success, a better understanding of the pivotal role of the tumor microenvironment in suppressing anticancer immunity and the exploration of treatment regimens using immune checkpoint inhibitors alone or in combination have finally led to the development of effective cancer immunotherapies and to improve survival of patients with certain types of advanced cancers. While the clinical experience with immune checkpoint inhibitors in gynecologic cancer patients remains limited, early signal of clinical activity strongly suggest that immunotherapy will play a significant role in the year to come in at least a subset of gynecologic cancer patients.
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Expert Opin Biol Ther · Jul 2016
ReviewMesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases.
Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives. ⋯ While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification.
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Expert Opin Biol Ther · Jan 2016
Ixekizumab: a new anti-IL-17A monoclonal antibody therapy for moderate-to severe plaque psoriasis.
Psoriasis is a common, systemic, inflammatory disease with prominent skin and joint manifestations. Interleukin 17A (IL-17A) has been identified as a key effector cytokine that mediates immunopathogenesis of psoriasis. Ixekizumab, a humanized monoclonal antibody that targets IL-17A, has been found in clinical trials to dramatically reduce signs and symptoms of moderate-to-severe plaque psoriasis. ⋯ This supports the idea that IL-17A plays a central role in psoriasis immunopathogenesis. While ixekizumab has been shown to be safe in trials up to 60 weeks, long-term safety data are not yet available. Because its efficacy is higher than all previously approved drugs for psoriasis thus far, approval and use of ixekizumab may lead to a treatment paradigm change for psoriasis, where clear or near clear skin becomes an acceptable and achievable treatment goal.
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Immune checkpoint inhibitors targeting programmed death protein 1 (PD-1) receptor and its ligand, PD-L1, have recently led to significant and durable improvements in the clinical outcomes of some types of cancers including lung cancer. ⋯ Pembrolizumab, demonstrated durable response and prolonged OS especially in NSCLC patients with high expression of PD-1, thereby suggests a new treatment paradigm. However, many issues remain to be explored, including the identification of other robust biomarkers that can accurately predict the immune-responsiveness of tumors. Along with the identification of predictive biomarkers, further understanding of the tumor microenvironment is necessary to improve treatment outcomes through combinations of immunotherapy or combined with other targeted therapies.
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Expert Opin Biol Ther · Jan 2016
ReviewCombination immune checkpoint blockade with ipilimumab and nivolumab in the management of advanced melanoma.
The use of immune checkpoint inhibitors for the treatment of advanced melanoma has evolved beyond monotherapies such as ipilimumab and nivolumab to combination strategies involving both. This combination approach results in response rates around 60% and superior progression-free survival compared with ipilimumab monotherapy (median 11.5 versus 2.9 months). ⋯ Efficacy for the combination approach is seen across a wide array of subgroups and occurs regardless of BRAF mutation status. Counterbalancing the apparent advantages, combination ipilimumab with nivolumab is associated with a high rate (55%) of grade 3/4 adverse events leading to discontinuation in a third of those treated. Most of these are manageable and do not appear to compromise durability of response. Overall survival information is currently immature but appears promising.