DiaPep277 peptide therapy in the context of other immune intervention trials in type 1 diabetes

Introduction: Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic β-cells. The aim of immune intervention is to arrest this autoimmune attack. DiaPep277, a major T-cell epitope of heat shock protein 60 (hsp60), has been shown to be effective in the modulation of the immune response in recent onset T1D and is the main focus of this review in the context of other ongoing trials using different approaches.

Areas covered: The authors performed a literature search of Pubmed listed publications (from the last 10 years) and a website search of the company licensing DiaPep277. DiaPep277 has been investigated in Phase I – III trials in humans. Phase II trials showed a significant preservation of β-cell function in adult T1D patients (but not children) with an absence of adverse effects and not accompanied by lower glycosylated haemoglobin (HbA1c) levels or reduced daily insulin requirement compared with placebo-treated patients.

Expert opinion: Administration of DiaPep277 is safe and represents a promising therapeutic strategy in patients with recent-onset T1D. The results of two large Phase III trials will tell us whether this therapy may change our current approach to treating T1D patients at diagnosis.     

Otelixizumab: a novel agent for the prevention of type 1 diabetes mellitus

Introduction: Type 1 diabetes mellitus is a chronic, progressive autoimmune disorder linked to numerous genetic and environmental factors. Insulin is the only treatment and preventative strategies do not currently exist. An obvious need exists to develop a safe regimen that suppresses the progression of the disease.

Areas covered: A MEDLINE search (1966–June 2011) was conducted for English-language articles using the terms ‘otelixizumab’, ‘anti-CD3 antibody’ and ‘prevention of type 1 diabetes mellitus’. Relevant literature on otelixizumab, an anti-CD3 monoclonal antibody, currently in Phase III clinical trials for prevention of T1DM is discussed.

Expert opinion: Studies suggest that a monoclonal antibody directed against CD3 mitigates the deterioration in insulin production and decreases the rise in insulin requirement in recent onset T1DM for up to five years. The benefit was most pronounced in younger patients and in those with higher initial β-cell function. Adverse effects were significant but transient. Otelixizumab shows great promise but leaves room for improvement. Results of ongoing trials will help define its role in the prevention of T1DM.     

DiaPep277 peptide therapy in the context of other immune intervention trials in type 1 diabetes

INTRODUCTION: Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic β-cells. The aim of immune intervention is to arrest this autoimmune attack. DiaPep277, a major T-cell epitope of heat shock protein 60 (hsp60), has been shown to be effective in the modulation of the immune response in recent onset T1D and is the main focus of this review in the context of other ongoing trials using different approaches. AREAS COVERED: The authors performed a literature search of Pubmed listed publications (from the last 10 years) and a website search of the company licensing DiaPep277. DiaPep277 has been investigated in Phase I - III trials in humans. Phase II trials showed a significant preservation of β-cell function in adult T1D patients (but not children) with an absence of adverse effects and not accompanied by lower glycosylated haemoglobin (HbA1c) levels or reduced daily insulin requirement compared with placebo-treated patients. EXPERT OPINION: Administration of DiaPep277 is safe and represents a promising therapeutic strategy in patients with recent-onset T1D. The results of two large Phase III trials will tell us whether this therapy may change our current approach to treating T1D patients at diagnosis.     

Immunomodulation with heat shock protein DiaPep277 to preserve beta cell function in type 1 diabetes – an update

Importance of the field: Type 1 diabetes is a chronic autoimmune disease in which pancreatic beta cells are selectively destroyed. Ultimately hyperglycemia develops and insulin substitution becomes necessary. Immunomodulation aims at arresting this autoimmune attack. DiaPep277, the major T-cell epitope of heat shock protein 60 (hsp60), has been shown to be effective as a modulator of the immune system in type 1 diabetes and is the focus of this review.

Areas covered in this review: A literature search of Pubmed listed publications covering 1990 – 2009 and a website search of the licensing company were performed.

What the reader will gain: DiaPep277 has been successfully employed in animal models and has been investigated in Phase I – III studies in humans. A combined analysis of the Phase II trials showed a significant preservation of beta cell function in adults without adverse effects, but HbA1c was not changed. A Phase III clinical trial is ongoing, and a second Phase III trial will start in early 2010. Addressing the underlying autoimmune process is the call of the future in type 1 diabetes.

Take home message: Use of Diapep277 is a promising therapeutic strategy currently being tested in Phase III trials.     

Efficacy and safety of otelixizumab use in new-onset type 1 diabetes mellitus

ABSTRACT

Introduction: Type 1 diabetes (T1DM) is an immune-mediated disease induced by antigen-specific T cells infiltrating pancreatic beta cells leading to the progressive loss of endogenous insulin secretion.

Areas covered: The identification of specific components of the autoimmune response favoured the implementation of several immunomodulatory therapies including antiCD3 monoclonal antibody (mAb) called otelixizumab. Otelixizumab is a chimeric monoclonal antibody that targets the ε-chain of the CD3T-lymphocyte surface receptor that has been developed with the aim of short therapeutic courses capable of inducing a remission of T1DM. Clinical trials have been carried out with otelixizumab to evaluate its safety and efficacy, but despite positive results of Phase I and II studies, the results of Phase III studies have been contradictory.

Expert opinion: High doses of otelixizumab have shown beneficial effects on beta cell function whereas a lower dose, which was tested to avoid the adverse effects associated with higher doses, was not effective on beta cells preservation. We believe that otelixizumab is a drug of potential interest for treating new onset T1DM patients and its use in combination with other immunomodulatory agents should be considered as a solution to circumvent adverse effects while maintaining efficacy.     

Effect of gamma aminobutyric acid (GABA) or GABA with glutamic acid decarboxylase (GAD) on the progression of type 1 diabetes mellitus in children: Trial design and methodology

BackgroundEvidence suggests that GABA may reduce pancreatic inflammation, protect β-cells from autoimmune destruction, and potentiate the regeneration of new β-cells in the setting of type 1 diabetes mellitus (T1DM). The enzyme GAD, also expressed in human pancreatic β-cells, is an antigenic target of reactive T cells. We hypothesized that treatment of children with recent onset T1DM with GABA or combination GABA with GAD will preserve β-cell function and ameliorate autoimmune dysregulation.MethodsThis is a one-year, prospective, randomized, double-blind, placebo-controlled trial. Ninety-nine patients aged 4–18 years with newly diagnosed T1DM are randomized into three treatment groups: 1) oral GABA twice daily in addition to two injections of recombinant GAD enzyme, 2) oral GABA plus placebo GAD injections, or 3) placebo GABA and placebo GAD. Patients are evaluated at baseline and months 1, 5, 8 and 12. Mixed meal tolerance testing is performed at all but the 8-month visit. Laboratory studies will assess indices of beta and alpha cell function, glycemic control, immunophenotyping, and diabetes-related autoantibodies.ResultsThe primary outcome is the effect on pancreatic β-cell function as measured by meal-stimulated c-peptide secretion compared between the treatment groups before and after one year of treatment. Secondary outcomes include: 1) fasting and meal stimulated glucagon and proinsulin levels, 2) response in insulin usage by participants, 3) indices of immune cell function, and 4) effect on autoantibodies GAD65, ICA512, and ZnT8.Conclusions: This trial will determine the safety and efficacy of GABA and combination GABA/GAD therapy to delay T1DM progression in children.     

Cell therapy for type 1 diabetes

ABSTRACT

Introduction

Type 1 diabetes (T1D) is a lifelong condition resulting from autoimmune destruction of insulin-producing β-cells. Islet or whole-pancreas transplantation is limited by the shortage of donors and need for chronic immune suppression. Novel strategies are needed to prevent β-cell loss and to rescue production of endogenous insulin.     

Amyloid-directed monoclonal antibodies for the treatment of Alzheimer’s disease: the point of no return?

Introduction: Two humanized monoclonal antibodies, bapineuzumab and solanezumab, directed against the N terminus and mid-region of β-amyloid (Aβ), respectively, were recently tested in large, long-term Phase III trials in patients with mild-to-moderate Alzheimer’s disease (AD).

Areas covered: This review discusses current clinical data on solanezumab, bapineuzumab and their failure in Phase III trials to show significant clinical benefits, as well as other monoclonal antibodies under investigation for AD.

Expert opinion: Solanezumab showed some beneficial cognitive effects in mildly affected AD patients and this subgroup of AD patients is currently being tested in another Phase III trial to this subgroup of AD patients to confirm previous encouraging observations. Two other monoclonal antibodies, gantenerumab, which preferentially binds to fibrillar Aβ, and crenezumab, which preferentially binds to soluble, oligomeric and fibrillar Aβ deposits, are being tested in secondary prevention trials in presymptomatic subjects with autosomal dominant AD mutations. Solanezumab is also being tested in a prevention study in asymptomatic older subjects, who have positive positron emission tomography scans for brain amyloid deposits. These ongoing secondary prevention trials will tell us if Aβ really plays a crucial role in the pathophysiology of AD.     

Bapineuzumab and solanezumab for Alzheimer's disease: is the ‘amyloid cascade hypothesis' still alive?

Introduction: The ‘amyloid cascade hypothesis' remains the leading hypothesis to explain the pathophysiology of Alzheimer's disease (AD). Immunotherapeutic agents have been developed to remove the neurotoxic amyloid β42 protein and prevent the hypothesized amyloid β42-induced neurotoxicity and neurodegeneration. The most notable of these immunotherapies are bapineuzumab and solanezumab.

Areas covered: This article briefly reviews the experimental agents in development for treatment of AD and then discusses the results of bapineuzumab and solanezumab in AD patients, as reported in preclinical studies, clinical trials and press releases.

Expert opinion: Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA). Solanezumab's two Phase III trials in AD patients failed to meet endpoints when analyzed independently. However, analysis of pooled data from both trials showed a significant reduction in cognitive decline in mild AD patients. The improvement was associated with an increase in plasma amyloid-β (Aβ) levels and a low incidence of ARIA in solanezumab-treated patients. The marginal benefits of solanezumab are encouraging to support continued evaluation in future studies, and offer small support in favor of the ongoing viability of the ‘amyloid cascade hypothesis' of AD.     

Albiglutide: a new GLP-1 analog for the treatment of type 2 diabetes

Importance of the field: Despite the wide array of treatments available, a significant number of patients with type 2 diabetes continue to remain uncontrolled. The discovery of the incretin hormones and their role in glucose homeostasis has brought about a new class of medications called the glucagon-like peptide-1 (GLP-1) analogs. This new class of medications provides the benefits of weight loss as well as a lack of hypoglycemia. However, the currently available agents require once or twice daily injections.

Areas covered in this review: Relevant literature will be discussed on albiglutide, a new GLP-1 analog in Phase III clinical trials. Several clinical trials examining the use of albiglutide as combination therapy are currently ongoing.

What the reader will gain: To date, results of clinical trials suggest that albiglutide may provide a more attractive dosing profile compared with the currently available GLP-1 analogs.

Take home message: The results of ongoing trials will help define the role of albiglutide in treating patients with type 2 diabetes.     

Liraglutide for type 2 diabetes mellitus

Introduction: Prevalence of type 2 diabetes mellitus (T2DM) is increasing. Management of this condition and minimizing the cardiovascular risks associated with it poses a significant burden on healthcare resources across the world. Currently available therapeutic agents are effective in glycemic management; however, the majority of these are associated with undesirable effects such as hypoglycemia and weight gain. Incretin-based therapies have been introduced over the last few years and are associated with less risk of hypoglycemia and weight gain.

Areas covered: This review includes current challenges in the management of T2DM, and an overview of glucagon-like peptide-1 (GLP-1)-based therapies, in particular the results of Phase III clinical studies of recently approved liraglutide. Apart from glycemic control, multifactorial interventions are needed to minimize the cardiovascular risks associated with T2DM. Liraglutide is effective in improving glycemic control measured by HbA1c and it is also shown to improve weight. Recently, the National Institute of Health and Clinical Excellence in the UK has approved liraglutide 1.2 mg dose in dual and triple therapy for T2DM.

Expert opinion: Liraglutide, a once-daily GLP-1 analog, has a definite role in selected patients with T2DM and the long-term cardiovascular safety is currently being ascertained in ongoing trials.     

Efficacy and Safety of Linagliptin in Subjects With Long-standing Type 2 Diabetes Mellitus (>10 Years): Evidence From Pooled Data of Randomized,Double-blind,Placebo-controlled,Phase III Trials

PurposeLong duration of type 2 diabetes mellitus (T2DM) is associated with progressive β-cell loss and may pose a challenge to maintenance of good glycemic control. This study aimed to assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in an understudied population of patients with long-standing T2DM.MethodsData from 202 individuals with T2DM for >10 years were pooled from 2 randomized, placebo-controlled, Phase III trials. Participants received either linagliptin 5 mg once daily (n = 122) or placebo (n = 80) for 24 weeks as an add-on to their current glucose-lowering therapy.FindingsLong-standing T2DM was associated with older age (mean [SD], 69.1 [10.0] years) and a high prevalence of diabetes-related complications (78% with diabetic kidney disease and 83% with macrovascular disease). The mean baseline glycosylated hemoglobin (HbA_1c) level was 8.22% (1.08%), and mean baseline fasting plasma glucose level was 161.8 (49.2) mg/dL. Linagliptin significantly improved glycemic control after 24 weeks, with a placebo-adjusted mean change in HbA_1c from baseline of −0.66% (95% CI, −0.95 to −0.38; P < 0.0001). This change was accompanied by a significant reduction in fasting plasma glucose, with a placebo-adjusted mean change from baseline of −15.5 mg/dL (95% CI, −29.6 to −1.3; P = 0.0323) at week 24. Overall, linagliptin was well tolerated, with drug-related adverse events in 21.3% and 16.3% of the linagliptin and placebo groups, respectively. Investigator-reported hypoglycemia occurred more often with linagliptin (25.4%) compared with placebo (12.5%). However, no severe hypoglycemic events were reported with linagliptin. Moreover, in patients not receiving concomitant sulfonylureas, the incidence of hypoglycemia with linagliptin (12.5%) was similar to that with placebo (12.2%). Patients’ mean weight remained unchanged in both groups.ImplicationsThis pooled analysis found that linagliptin was well tolerated and significantly improved hyperglycemia in a clinically challenging population of patients with long-standing T2DM (>10 years). Although T2DM is commonly associated with diminished β-cell function, the extent of glucose lowering was similar to that in linagliptin trials, which largely included patients in earlier stages of the disease. Thus, this observation supports the hypothesis that regulation of glucagon release from pancreatic α cells may be of particular relevance for improving hyperglycemia in patients with long-term T2DM (NCT01194830 and NCT01084005).     

Thymosin β4 attenuates microcirculatory and hemodynamic destabilization in sepsis

Objective: The actin polymerization regulator Thymosin β4 (Tβ4) has been shown to be involved in angiogenesis, wound healing, cell survival and anti-inflammatory responses. We have previously shown that Tβ4 is capable of recruiting pericytes, thus stabilizing the endothelial barrier function. Here, we analyzed whether treatment with Tβ4 is able to reduce the pericytes loss in lipopolysaccharides (LPS)-induced sepsis and to improve the hemodynamic function and survival in C57BL/6 mice.

Methods: Fourteen days before LPS injection, the mice were injected with an adeno-associated virus carrying the Tβ4 (rAAV.Tβ4) or LacZ gene (rAAV.LacZ). A sepsis-severity score was assessed, and non-invasive hemodynamic and permeability measurements were performed. Heart and muscle samples were analyzed for PECAM-1⁺ capillaries and NG2⁺pericytes.

Results: At 36 h, there was a decrease of sepsis severity score in rAAV.Tβ4-treated animals as compared to rAAV.LacZ-treated control. rAAV.Tβ4-treated animals displayed lower perivascular leakage and higher blood pressure compared to control. Of note, the rAAV.Tβ4 group showed a higher pericyte count in heart and peripheral muscle samples. Finally, Tβ4-treatment reduced mortality compared to control.

Conclusion: The data indicate a preventive role of Tβ4 in septic hypercirculation and highlight Tβ4 as a potential therapeutic target in severe sepsis.     

Solanezumab for Alzheimer's disease

Introduction: Alzheimer's disease (AD) is a debilitating neurodegenerative illness affecting over 35 million people worldwide. Solanezumab is a monoclonal antibody that binds to β-amyloid (Aβ), a protein that plays a key role in the pathogenesis of AD. The drug is currently being investigated in Phase III trials as a disease-modifying treatment for AD.

Areas covered: This paper reviews literature on solanezumab that is available in PubMed from 2008 to 2010, other treatment trials in clinicaltrials.gov and published abstracts from conferences. The article also provides a discussion of the early trials of AN1792 and an overview of the immunotherapies currently in development. The authors provide the reader with a critical appraisal of the to-date clinical trial data on solanezumab and its implications for the broader field of immunotherapies for AD.

Expert opinion: Solanezumab can neutralize soluble Aβ peptides, which may represent the more neurotoxic of the Aβ species. Phase II findings support the compound's safety, which has been a concern for some Aβ immunotherapies. Cerebrospinal and plasma biomarker changes with solanezumab treatment are encouraging. Results of the ongoing Phase III trials will be instrumental in determining the drug's clinical significance.     

Clarifying the role of incretin-based therapies in the treatment of type 2 diabetes mellitus

BackgroundGlucose homeostasis is the result of a complex interaction of a spectrum of hormones, including insulin, glucagon, amylin, and the incretins. Incretins are released by enteroendocrine cells in the intestine in response to a meal. Incretin dysfunction, along with a number of other defects, has been implicated in contributing to the pathogenesis of type 2 diabetes mellitus (T2DM). Therapies that restore incretin activity may reduce the pathophysiologic consequences of diabetes.ObjectivesThe aim of this article was to review incretin physiology and studies of incretin therapy with glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors that were developed to specifically address the blunted incretin response in patients with T2DM.MethodsRelevant English-language publications between 1995 and 2010 were identified through a search of the MEDLINE and EMBASE databases using the search terms incretin, type 2 diabetes mellitus, GLP-1, glucose-dependent insulinotropic polypeptide, and DPP-4. Review articles and preclinical and clinical trials that described relevant details of the epidemiology of diabetes and incretin physiology in health and in T2DM were selected for review and inclusion. Clinical trials were used to describe the clinical efficacy and safety of the GLP-1 receptor agonists and DPP-4 inhibitors in patients with T2DM. An occasional systematic review article and/or meta-analysis summarizing numerous clinical trials of a particular agent was selected for summarizing key data.ResultsPharmacologic modulation of incretin pathophysiology by GLP-1 receptor agonists and DPP-4 inhibitors significantly improved glycemic control, benefited β-cell function, improved dyslipidemia, and lowered the risk of hypoglycemia compared with insulin and sulfonylureas. Unlike the DPP-4 inhibitors, GLP-1 receptor agonist therapy also produced weight loss, an important consideration given the close association among T2DM, overweight/obesity, and cardiovascular disease. The most common adverse events with GLP-1 receptor agonist therapy included nausea (28%–44%), vomiting (13%–17%), and diarrhea (11%–17%), which generally reduced in incidence and severity with continued therapy. The tolerability profile of the DPP-4 inhibitors was very good, with the incidence of adverse events similar to that of placebo. There was a suggestion of an increased incidence of nasopharyngitis versus placebo (5%–6% vs 3%–4%) with sitagliptin and urinary tract infection (6.8% vs 6.1% with placebo) and headache with saxagliptin (6.5% vs 5.9% with placebo).ConclusionThe 2 incretin drug classes provided effective and consistent glycemic control with a good tolerability profile. These agents might also improve long-term β-cell function and either reduce body weight or be weight neutral. Their role in the therapeutic armamentarium of T2DM is evolving as their potential strengths and weaknesses become better defined.     

Bapineuzumab

Importance of the field: Alzheimer's disease is the leading cause of dementia in the elderly, and there is no disease-modifying therapy yet available. Immunotherapy directed against the β-amyloid peptide may be capable of slowing the rate of disease progression. Bapineuzumab, an anti-β-amyloid monoclonal antibody, will be the first such agent to emerge from Phase III clinical trials.

Areas covered in this review: The primary literature on bapineuzumab from 2009 and 2010 is reviewed in its entirety, along with the literature on AN1792, a first-generation anti-β-amyloid vaccine, from 2003 to 2009. Other Alzheimer's disease immunotherapeutics currently in development, according to www.clinicaltrials.gov, are also discussed.

What the reader will gain: In addition to a critical appraisal of the Phase II trial results for bapineuzumab, this review considers the broader field of immunotherapy for Alzheimer's disease as a whole, including the challenges ahead.

Take home message: Bapineuzumab appears capable of reducing the cerebral β-amyloid peptide burden in patients with Alzheimer's disease. However, particularly in APOE ?4 carriers, its ability to slow disease progression remains uncertain, and vasogenic edema – a dose-limiting and potentially severe adverse reaction – may limit its clinical applicability.     

Effects of incretin-based therapies on β-cell function in type 1 diabetes mellitus: a systematic review and meta-analysis

AimTo assess the effects of incretin-based therapies on β-cell function in patients with type 1 diabetes mellitus (T1DM).MethodsWe searched the PubMed, Cochrane Library, Embase, and Web of Knowledge databases for eligible randomized clinical trials published up to July 2021. The inclusion criteria were patients with T1DM or latent autoimmune diabetes in adults, patients treated with dipeptidyl peptidase-4 inhibitors or glucagon like peptide-1 receptor agonists, and outcomes included one of the following: fasting plasma glucose, fasting C-peptide, postprandial C-peptide, C-peptide area under the curve (AUC), homeostasis model assessment for β cell function, and insulin resistance. The effects were analyzed using a random effect model with STATA 11.0.ResultsEight trials including 427 participants were included in the final analysis. A pooled analysis found no significant difference in fasting plasma glucose, fasting C-peptide, postprandial C-peptide, or C-peptide AUC between patients treated with incretin-based therapies and placebo. The two trials that reported changes in 2-hour postprandial C-peptide and two of the four trials that reported changes in C-peptide AUC reported increases after incretin-based therapies.ConclusionThis meta-analysis showed that incretin-based therapies did not preserve β-cell function in patients with T1DM.     

VB-111 for cancer

Introduction: Antibody, small molecule and protein inhibitors of angiogenesis are used in the management of several cancers. These do not specifically target tumor vascularity, and resistance can be problematic. VB-111 is a vascular-targeting agent consisting of a non-replicating adenovirus vector with a pre-proendothelin-1 promoter that encodes an apoptotic receptor.

Areas covered: The rationale and design of VB-111, its mechanism of action, and preclinical studies examining antitumor activity, toxicology and pharmacodynamics are reviewed. Phase I and Phase II clinical trials are also reviewed.

Expert opinion: VB-111 is a vascular-targeting gene therapeutic that is both tissue- and condition-specific, with effects limited to endothelial cells undergoing angiogenesis. Systemic administration produces selective destruction of tumor vascularity. Synergistic antitumor activity can be observed when combined with chemotherapy. VB-111 has been found to be safe and well tolerated in a Phase I clinical trial in patients with advanced solid tumors. Phase II clinical trials are in progress. VB-111 is novel agent for cancer that may have application as monotherapy and in combination with other therapies.     

Current treatments and strategies for type 2 diabetes: Can we do better with GLP-1 receptor agonists?

Abstract

Diet, lifestyle modification, and pharmacotherapy with metformin are appropriate initial treatments for many patients with type 2 diabetes (T2DM). However, most individuals do not maintain glycemic control with metformin alone. Addition of other oral antidiabetes drugs (OADs), including sulfonylurea, meglitinide, or thiazolidinedione, is often the next step. Newer options, including incretin-based glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, offer important benefits as monotherapies or in combination with OADs, with low risk for hypoglycemia. Reductions in glycated hemoglobin (A1C) have been reported among patients treated with GLP-1 RAs (exenatide, ?0.8 to ?1.1%; liraglutide, ?0.8 to ?1.6%), as has weight loss (exenatide, ?1.6 to ?3.1 kg; liraglutide, ?1.6 to ?3.2 kg). GLP-1 RAs also stimulate β-cell responses and have positive effects on cardiovascular risk factors often present in patients with T2DM. The most common adverse events associated with GLP-1 RAs are nausea, which diminishes over time, and hypoglycemia (when used in combination with a sulfonylurea). A large number of trials demonstrated benefits of GLP-1 RAs, suggesting they could provide suitable treatment options for patients with T2DM.     

AE37: a novel T-cell-eliciting vaccine for breast cancer

Introduction: Immunotherapy, including vaccines targeting the human EGFR2 (HER-2/neu) protein, is an active area of investigation in combatting breast cancer. Several vaccines are currently undergoing clinical trials, most of which are CD8⁺ T-cell-eliciting vaccines. AE37 is a promising primarily CD4⁺ T-cell-eliciting HER-2/neu breast cancer vaccine currently in clinical trials.

Areas covered: This article reviews preclinical investigations as well as findings from completed and ongoing Phase I and Phase II clinical trials of the AE37 vaccine.

Expert opinion: Clinical trials have shown the AE37 vaccine to be safe and capable of generating peptide-specific, durable immune responses. This has been shown in patients with any level of HER-2/neu expression. Early clinical findings suggest there may be benefit to AE37 vaccination in preventing breast cancer recurrence.