Vaccine against arteriosclerosis: an update

Chyu, Kuang‐Yuh; Dimayuga, Paul C.; Shah, Prediman K.

doi:10.1177/2051013617693753

Cited by 37 publications

(20 citation statements)

References 76 publications

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“…Moreover, several targets have been explored as a novel antiatherosclerosis vaccine therapy. For example, apolipoprotein B100 derived peptides or using modified LDL as antigen, have been shown to reduce atherosclerotic lesions in experimental models [30]. All of these potential immunomodulatory therapies need elaborate clinical evaluation and should be directly tested by randomized trials.…”

Section: Other Immunomodulatory Therapiesmentioning

confidence: 99%

Critical roles of inflammation in atherosclerosis

Moriya

2019

Journal of Cardiology

257

177

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There is accumulating evidence that vascular inflammation plays critical roles in pathophysiology of atherosclerosis. It is widely accepted that both innate and adaptive immune responses are important for initiation and progression of atherosclerosis, which mainly consist of monocytes, macrophages, neutrophils, T lymphocytes, and B lymphocytes. Moreover, inflammatory biomarkers such as high-sensitivity C-reactive protein and interleukin-6 are known to predict future cardiovascular events, as well as conventional low-density or high-density lipoprotein cholesterol. Thus, current understanding of the inflammatory mechanisms of atherosclerosis have led us to explore novel therapeutic approaches that reducing vascular inflammation itself could lower the rates of critical cardiovascular events. To address the inflammatory hypothesis of atherosclerosis, results of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial have been recently reported that anti-inflammatory therapy using canakinumab, a monoclonal antibody targeting interleukin-1β, significantly reduced recurrent cardiovascular events for secondary prevention of myocardial infarction at high inflammatory risk. In this review, we will first outline the mechanisms of atherosclerosis, especially focusing on their inflammatory aspects. Then we will introduce several critical inflammatory biomarkers that contribute to risk stratification of clinical cardiovascular events. Lastly, we will discuss potentiality and future perspectives of reducing inflammation as a novel therapeutic target for atherosclerotic cardiovascular diseases.

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Section: Other Immunomodulatory Therapiesmentioning

confidence: 99%

Critical roles of inflammation in atherosclerosis

Moriya

2019

Journal of Cardiology

257

177

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“…[8] Three bsAbs, blinatumomab, catumaxomab and emicizumab are approved by the US Food and Drug Administration. [8,9] The bispecific format is a combination of two distinct variable regions derived from two different parental monospecific antibodies. The ability to simultaneously bind two different epitopes enables a variety of potential modes of actions, such as an improved cytotoxic potential by bridging cells in-trans, synergistic effects, receptor crosslinking for enhanced inhibition or degradation and higher binding specificity, resulting, for example, in enhanced tumor selectivity.…”

Section: Introductionmentioning

confidence: 99%

Intein mediated high throughput screening for bispecific antibodies

Hofmann

Schmidt

Ciesielski

et al. 2020

mAbs

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Bispecific antibodies comprise extremely diverse architectures enabling complex modes of action, such as effector cell recruitment or conditional target modulation via dual targeting, not conveyed by monospecific antibodies. In recent years, research on bispecific therapeutics has substantially grown. However, evaluation of binding moiety combinations often leads to undesired prolonged development times. While high throughput screening for small molecules and classical antibodies has evolved into a mature discipline in the pharmaceutical industry, dual-targeting antibody screening methodologies lack the ability to fully evaluate the tremendous number of possible combinations and cover only a limited portion of the combinatorial screening space. Here, we propose a novel combinatorial screening approach for bispecific IgG-like antibodies to extenuate screening limitations in industrial scale, expanding the limiting screening space. Harnessing the ability of a protein trans-splicing reaction by the split intein Npu DnaE, antibody fragments were reconstituted within the hinge region in vitro. This method allows for fully automated, rapid one-pot antibody reconstitution, providing biological activity in several biochemical and functional assays. The technology presented here is suitable for automated functional and combinatorial high throughput screening of bispecific antibodies.

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“…In regards anti-atherosclerosis vaccine development, several targets have been considered (10,11,22). ApoB-100-derived peptides, especially p210 prototype, have shown reduction of aortic plaques in murine models via activation of CD8 + T cells and Tregs (22). Several trials have been conducted using modified LDL as antigen, resulting in reduction of atherosclerosis burden (22).…”

Section: The Future Of Atheroprotectionmentioning

confidence: 99%

“…ApoB-100-derived peptides, especially p210 prototype, have shown reduction of aortic plaques in murine models via activation of CD8 + T cells and Tregs (22). Several trials have been conducted using modified LDL as antigen, resulting in reduction of atherosclerosis burden (22). Another venue of investigation has been focusing in mononuclear cell recruitment and migration towards the sub-endothelium, such as the multi-epitope vaccine targeting CD99, CD81 and CD99L2 (23).…”

Section: The Future Of Atheroprotectionmentioning

confidence: 99%