Elotuzumab in the treatment of relapsed and refractory multiple myeloma

Multiple myeloma (MM) is still considered an incurable disease. However, drugs with different mechanisms of action that can improve the efficiency of treatment offer hope. Still, there are concerns about an unacceptable increase in toxicity with such regimens. The results of recently published clinical studies of elotuzumab in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone confirm previous hopes to improve the effect of that treatment. Humanized monoclonal antibodies aimed at SLAMF7 stimulate natural killer cells to fight against MM cells. Elotuzumab used in combination with lenalidomide/dexamethasone or with pomalidomide/dexamethasone is approved by the US FDA to treat patients with relapsed and/or refractory MM. The article is a summary of the recent knowledge about the possibility of using elotuzumab in the treatment of relapsed and/or refractory MM and shows its potential uses in the future.

CGRP: from history to clinical application - A review

The role of calcitonin gene-related peptide (CGRP) and its receptor have played an important role in migraine for the last decades due to development of therapies that target their receptors at the trigeminal pain system, aiming at prevention or relief of acute migraine attacks. At first, CGRP receptor antagonists, called gepants have demonstrated appropriate effectiveness. In addition, they did not cause vasoconstriction, one of the drawbacks of triptans. However, their use had to be discontinued due to the risk of liver toxicity. Humanized monoclonal antibodies towards CGRP and the CGRP receptor have been developed as an alternative approach to block CGRP transmission. Still, there are some questions not fully answered as where CGRP and its receptor are located, how they influence the mechanisms of migraine attacks and if the blood brain barrier has any sort of importance. There is still much to learn about CGRP and migraine pathophysiology, especially its anatomical target sites and anti-CGRP agents. This paper presents a review of CGRP, including a brief history, focusing in CGRP mechanism, updates and future treatments.

Dendritic Cells and SARS-CoV-2 Infection: Still an Unclarified Connection

The ongoing pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has so far infected about 2.42 × 107 (as at 27 August 2020) subjects with more than 820,000 deaths. It is the third zoonotic coronavirus-dependent outbreak in the last twenty years and represents a major infective threat for public health worldwide. A main aspect of the infection, in analogy to other viral infections, is the so-called “cytokine storm”, an inappropriate molecular response to virus spread which plays major roles in tissue and organ damage. Immunological therapies, including vaccines and humanized monoclonal antibodies, have been proposed as major strategies for prevention and treatment of the disease. Accordingly, a detailed mechanistic knowledge of the molecular events with which the virus infects cells and induces an immunological response appears necessary. In this review, we will report details of the initial process of SARS-CoV-2 cellular entry with major emphasis on the maturation of the spike protein. Then, a particular focus will be devoted to describe the possible mechanisms by which dendritic cells, a major cellular component of innate and adaptive immune responses, may play a role in the spread of the virus in the human body and in the clinical evolution of the disease.

Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review

The need for proven disease-specific treatments for the novel pandemic coronavirus SARS-CoV-2 necessitates a worldwide search for therapeutic options. Since the SARS-CoV-2 virus shares extensive homology with SARS-CoV and MERS-CoV, effective therapies for SARS-CoV and MERS-CoV may also have therapeutic potential for the current COVID-19 outbreak. To identify therapeutics that might be repositioned for treatment of the SARS-CoV-2 disease COVID-19, we strategically reviewed the literature to identify existing therapeutics with evidence of efficacy for the treatment of the three coronaviruses that cause severe respiratory illness (SARS-CoV, MERS-CoV, and SARS-CoV-2). Mechanistic and in vitro analyses suggest multiple promising therapeutic options with potential for repurposing to treat patients with COVID-19. Therapeutics with particularly high potential efficacy for repurposing include camostat mesylate, remdesivir, favipiravir, tocilizumab, baricitinib, convalescent plasma, and humanized monoclonal antibodies. Camostat mesylate has shown therapeutic potential, likely by preventing viral entry into epithelial cells. In early research, the targeted antivirals remdesivir and favipiravir appear to benefit patients by decreasing viral replication; clinical trials suggest that remdesivir speeds recovery from COVID-19. Tocilizumab and baricitinib appear to improve mortality by preventing a severe cytokine storm. Convalescent plasma and humanized monoclonal antibodies offer passive immunity and decreased recovery time. This review highlights potential therapeutic options that may be repurposed to treat COVID-19 and suggests opportunities for further research.

Anti-CGRP monoclonal antibodies: a breakthrough in the treatment of migraine

To date, the prophylactic treatment of migraine has included only nonspecific drugs of various pharmacological groups: the beta-blockers propranolol and metoprolol, the anticonvulsants topiramate and valproic acid, the antidepressants amitriptyline and venlafaxine, candesartan, and Ona botulinum toxin A. As these drugs were developed for treatment of other diseases, their use was associated with adverse effects: decreased blood pressure, mental retardation, weight increase, nausea, and some others. CGRP is a neuropeptide that was regarded as the main biomarker of migraine as its level in this disease rise. The emergence of humanized monoclonal antibodies has opened up the possibility of blocking the action of CGRP and developing a new class of drugs that includes fremanezumab, erenumab, galcanezumab, and eptinezumab. Anti-CGRP monoclonal antibodies can be prescribed to patients with chronic and episodic migraine. The use of anti-CGRP monoclonal antibodies in clinical studies was associated with a small number of adverse effects, with severe adverse reactions being extremely rare.

Recent Advances in the Development of Vaccines for Diabetes, Hypertension, and Atherosclerosis

Vaccines are commonly used in the prevention of infectious diseases. The basic principle of vaccination is to use specific antigens, endogenous or exogenous to stimulate immunity against the specific antigens or cells producing them. Autoantigen or oligo vaccination has been used for disease animal models. More recently humanized monoclonal antibodies have been successfully used for the treatment of neoplastic disorders or familial hypercholesterolemia. Humanized monoclonal antibody therapy needs repeated injection, and the therapy is expensive. Therapeutic vaccination can lead to persistent immunized or immune tolerant against the therapeutic molecule(s) or site. However, immunization against those endogenous substances may also elicit persistent autoimmune reaction or destruction that do harm to health. Therefore, rigorous studies are needed before any clinical application. In this review, we briefly reviewed vaccines used in protection against common metabolic diseases including atherosclerosis, hypertension, and diabetes mellitus.