Delving into the Latest Updates on Multimeric Biotherapeutics, Inc. with Synapse

概览

疾病领域	数量

肿瘤	2
感染	1

排名前五的药物类型	数量

疫苗	1
合成多肽	1

关联

4

项与 Multimeric Biotherapeutics, Inc. 相关的药物

FortiVac

靶点-

作用机制

免疫刺激剂

在研机构

Multimeric Biotherapeutics, Inc.

原研机构

Multimeric Biotherapeutics, Inc.

在研适应症

感染 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

MegaOX40L (Multimeric Biotherapeutics, Inc.)

靶点-

作用机制-

在研机构

Multimeric Biotherapeutics, Inc.

原研机构

Multimeric Biotherapeutics, Inc.

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期-

MegaCD40L

靶点-

作用机制

免疫刺激剂

在研机构-

原研机构

Apoxis SA

在研适应症-

非在研适应症

肿瘤

最高研发阶段终止

首次获批国家/地区-

首次获批日期-

100 项与 Multimeric Biotherapeutics, Inc. 相关的临床结果

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0 项与 Multimeric Biotherapeutics, Inc. 相关的专利（医药）

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7

项与 Multimeric Biotherapeutics, Inc. 相关的文献（医药）

2019-05-01·The Journal of Immunology

CD40 ligand (CD40L) multi-trimer antigen fusion protein (MagaVax) as a vaccine design for high-level CD8+ T cell responses

作者: Studer, Sean ; Kornbluth, Richard S ; Adase, Christopher ; Hamilton, Victoria Snarsky

AbstractDendritic cells (DCs) can take up antigen via a number of routes. Of these, several studies have shown antigen uptake via the CD40 receptor generates some of the strongest CD8+ T cell responses. At the same time, stimulation through CD40 activates DCs for cross-presentation and heightened antigen presentation. Consequently, it is desirable to combine the CD40 targeting of antigen and a CD40 stimulant into a single vaccine formulation. When the CD40 stimulant is CD40 ligand (CD40L, CD154), it is important to use a multi-trimer complex that clusters CD40 in the DC membrane, thereby engaging downstream signaling pathways. Such a multi-trimer form of CD40L can be provided by fusing the extracellular domain of CD40L with the body of surfactant protein D (SPD), a self-assembling 12-chain soluble molecule with 4 trimeric “arms.” When an antigen sequence is included within the SPD arm, the entire protein complex is termed “Multi-trimer AntiGen Adjuvant Vaccine (Vax)” or “MagaVax.” Studies in mice have shown that MagaVax elicits very high levels of antigen-specific CD8+ T cells with high TCR avidity and functional activity. MagaVax can be effectively delivered as a DNA vaccine i.m. and even more effectively using an adenoviral (Ad5) vector. For a MagaVax encoding HIV-1 Gag, vaccination with Ad5-MagaVax-Gag led to complete protection (“sterilizing immunity”) from Vaccinia-Gag challenge (i.e., 7 log reduction of tissue virus). Thus far, MagaVax formulations have been made for HIV-1 Gag, Ebola, malaria, hepatitis B virus (HBV), and tumor-specific neoantigens. In all of these cases, there may be a clinical benefit for a vaccine that elicits very strong CD8+ T cell responses.

2017-05-01·The Journal of Immunology

Multimeric Soluble 4-1BBL as a T Cell Stimulator for Adoptive Immunotherapy.

作者: Hamilton, Victoria Snarsky ; Stone, Geoffrey W ; Kornbluth, Richard S

AbstractMembers of the TNF SuperFamily of ligands (TNFSFs) have significant potential as immuno-oncology agents. The TNFSFs are trimeric membrane proteins that can be cleaved into soluble single trimers. While the soluble single trimers can be easily prepared and studied, they have little or no activity in vivo. This deficiency is caused by the need to cluster their cognate receptors in the plane of the membrane in order to induce a supramolecular signaling complex on the cytoplasmic side of the plasma membrane. For the TNFSF ligands, this requires that they be used as many-trimer multimers that mimic the natural expression of many trimers on the surface of stimulating cells. To meet this need, we prepared fusion proteins comprised of the extracellular domains of TNFSF ligands joined to a natural protein that provides a multimerization scaffold. When surfactant protein D (SP-D) is used as a scaffold, the result is a 4-trimer TNFSF ligand product (UltraLigand™). Our published studies have described such multimeric forms of CD40L, OX40L, GITRL, CD27L/CD70, BAFF, RANKL, and TRAIL and shown that they are highly active in vitro and in vivo. As an extension of this work, 4-trimer forms of murine and human 4-1BBL (CD137L, TNFSF9) were constructed and expressed in CHO cells. As a co-stimulatory molecule, SP-D-4-1BBL (Ultra4-1BBL) activated both CD4+ and CD8+ T cells and promoted the growth of NK cells in vitro. Given the interest in 4-1BB (CD137) as a marker of therapeutically effective tumor-infiltrating lymphocytes (TILs), SP-D-4-1BBL should be a useful should be a useful growth factor for TIL manufacturing and T cell culturing in general.

2014-02-01·Journal of Virology2区 · 医学

Vaccination with a Fusion Protein That Introduces HIV-1 Gag Antigen into a Multitrimer CD40L Construct Results in Enhanced CD8 ⁺ T Cell Responses and Protection from Viral Challenge by Vaccinia-Gag

2区 · 医学

Article

作者: Kornbluth, Richard S. ; Raffa, Francesca N. ; Williams, Cindi-Ann ; Termini, James M. ; Stone, Geoffrey W. ; Gupta, Sachin

ABSTRACT CD40 ligand (CD40L, CD154) is a membrane protein that is important for the activation of dendritic cells (DCs) and DC-induced CD8 + T cell responses. To be active, CD40L must cluster CD40 receptors on responding cells. To produce a soluble form of CD40L that clusters CD40 receptors necessitates the use of a multitrimer construct. With this in mind, a tripartite fusion protein was made from surfactant protein D (SPD), HIV-1 Gag as a test antigen, and CD40L, where SPD serves as a scaffold for the multitrimer protein complex. This SPD-Gag-CD40L protein activated CD40-bearing cells and bone marrow-derived DCs in vitro . Compared to a plasmid for Gag antigen alone (pGag), DNA vaccination of mice with pSPD-Gag-CD40L induced an increased number of Gag-specific CD8 + T cells with increased avidity for major histocompatibility complex class I-restricted Gag peptide and improved vaccine-induced protection from challenge by vaccinia-Gag virus. The importance of the multitrimeric nature of the complex was shown using a plasmid lacking the N terminus of SPD that produced a single trimer fusion protein. This plasmid, pTrimer-Gag-CD40L, was only weakly active on CD40-bearing cells and did not elicit strong CD8 + T cell responses or improve protection from vaccinia-Gag challenge. An adenovirus 5 (Ad5) vaccine incorporating SPD-Gag-CD40L was much stronger than Ad5 expressing Gag alone (Ad5-Gag) and induced complete protection (i.e., sterilizing immunity) from vaccinia-Gag challenge. Overall, these results show the potential of a new vaccine design in which antigen is introduced into a construct that expresses a multitrimer soluble form of CD40L, leading to strongly protective CD8 + T cell responses.

100 项与 Multimeric Biotherapeutics, Inc. 相关的药物交易

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100 项与 Multimeric Biotherapeutics, Inc. 相关的转化医学

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药物发现

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临床前

其他

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当前项目

药物(靶点)	适应症	全球最高研发状态

FortiVac	感染更多	临床前
MegaOX40L (Multimeric Biotherapeutics, Inc.)	肿瘤更多	药物发现
pSP-D-CD40L ( CD40L )	肿瘤更多	无进展
MegaCD40L	肿瘤更多	无进展