Expert opinion on biological therapy
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Expert Opin Biol Ther · Jun 2013
ReviewAnti-programmed death-1 and anti-programmed death-ligand 1 antibodies in cancer therapy.
Multiple agents targeting the immune "checkpoint" programmed death-1 (PD-1) pathway have demonstrated early evidence of durable clinical activity and an encouraging safety profile in patients with various tumor types, including some cancers, such as non-small-cell lung cancer, historically perceived as non-immunogenic and thus nonresponsive to immunotherapy. ⋯ Rather than targeting the tumor directly, immunotherapies inhibiting PD-1 pathway signaling modulate the antitumor immune response. Indeed, these agents have already demonstrated promising antitumor activity and manageable toxicity in various cancers. If future data continue to support encouraging clinical profiles of anti-PD-1 and anti-programmed death-ligand 1 antibodies, the current paradigm of cancer therapy may shift. In select patient populations (ideally identified by a predictive biomarker), PD-1 pathway-targeted immunotherapy has the potential to serve as the backbone of cancer treatment, and trials evaluating combinations with chemotherapy and/or molecularly targeted therapies will determine whether additive or even synergistic responses can be achieved.
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Expert Opin Biol Ther · May 2013
ReviewPertuzumab : evolving therapeutic strategies in the management of HER2-overexpressing breast cancer.
HER2 overexpression or amplification is present in approximately one-fifth of breast cancers and historically was associated with aggressive disease and poorer prognosis. The introduction of the humanized monoclonal antibody trastuzumab dramatically improved disease-free survival (DFS) and overall survival (OS) in this subgroup. As the majority of patients with metastatic disease ultimately develop resistance to trastuzumab, a need exists for more effective targeted therapies. Pertuzumab is an anti-HER2/neu-targeted therapy in the late stages of clinical development. The combination of pertuzumab, trastuzumab and docetaxel has been found to have an OS benefit in patients with HER2 positive metastatic breast cancer (MBC) when used in the first-line setting. This reflects a new standard of care, and pertuzumab was recently approved for this indication by the Food and Drug Administration (FDA). The efficacy of pertuzumab and trastuzumab in conjunction with chemotherapy is currently being evaluated in the adjuvant setting. ⋯ Pertuzumab, in combination with the humanized monoclonal antibody trastuzumab, and docetaxel is a standard of care for patients with previously untreated metastatic breast cancer based on the CLEOPATRA study showing a survival benefit. There is no increase in cardiac toxicity with the combined HER2-targeted therapy. Future issues will address appropriate sequencing and combination with other anti-HER2-targeted therapies and/or chemotherapy.
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Expert Opin Biol Ther · Apr 2013
ReviewStem cell therapy for chronic heart failure: an updated appraisal.
Significant advances have been made to understand the mechanisms involved in cardiac cell-based therapies. The early translational application of basic science knowledge has led to several animal and human clinical trials. The initial promising beneficial effect of stem cells on cardiac function restoration has been eclipsed by the inability of animal studies to translate into sustained clinical improvements in human clinical trials. ⋯ Several questions remain unanswered, and this limits our ability to understand basic mechanisms involved in stem cell therapeutics. Human studies have revealed critical unresolved issues. Further elucidation of the proper timing, mode delivery and prosurvival factors is imperative, if the field is to advance. The limited benefits seen to date are simply not enough if the potential for substantial recovery of nonfunctioning myocardium is to be realized.
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Expert Opin Biol Ther · Feb 2013
ReviewMonoclonal antibodies for asthma and chronic obstructive pulmonary disease.
In asthma and chronic obstructive pulmonary disease (COPD), the inflammation in the airways cannot always be controlled with conventional therapies, such as inhaled corticosteroids. Addition of more specific anti-inflammatory therapies, such as monoclonal antibodies, against inflammation pathways might improve the disease outcome. ⋯ The current use of omalizumab in asthma provides a good example on the potential therapeutic role of monoclonal antibodies in both asthma and COPD. There are many other monoclonal antibodies which are currently investigated as possible therapies in these diseases. The identification of the disease subsets in which such antibodies might exert the maximum benefit opens the door for personalized medicine and for targeted biological therapy in asthma and COPD.
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Expert Opin Biol Ther · Dec 2012
ReviewAn update on vaccines for tuberculosis - there is more to it than just waning of BCG efficacy with time.
Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide. ⋯ It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.