07 May 2020

CD24Fc protects against viral pneumonia in simian immunodeficiency virus-infected Chinese rhesus monkeys

Viral pneumonia is a major cause of mortality caused by both systemic and respiratory infections. The danger-associated molecular patterns (DAMPs) released during cell death in viral infection may cause a self-propagating inflammatory response with lasting lung damage. The CD24–Siglec 10/G interaction is an emerging immune checkpoint that regulates inflammation caused by DAMPs.1,2,3 While we have demonstrated that fortifying this immune checkpoint can reduce inflammation in the colon,4 joints5 and central nervous system,6 it is unclear whether CD24Fc can protect against pneumonia. To address this issue, we evaluated the lung pathology of simian immunodeficiency virus (SIV)-infected rhesus monkeys that received either normal saline (NS) or CD24Fc.

01 August 2019

Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy.

It remains unclear why the clinically used anti-CTLA-4 antibodies, popularly called checkpoint inhibitors, have severe immunotherapy-related adverse effects (irAEs) and yet suboptimal cancer immunotherapeutic effects (CITE). Here we report that while irAE-prone Ipilimumab and TremeIgG1 rapidly direct cell surface CTLA-4 for lysosomal degradation, the non-irAE-prone antibodies we generated, HL12 or HL32, dissociate from CTLA-4 after endocytosis and allow CTLA-4 recycling to cell surface by the LRBA-dependent mechanism.

01 December 2018

How Does an Anti-CTLA-4 Antibody Promote Cancer Immunity?

Anti-CTLA-4 antibodies can induce lasting protection for some melanoma patients. However, their therapeutic potential is limited by significant immunotherapy-related adverse effects (irAE). Here, we argue that the therapeutic effect may be based on an agonist activity that is fundamentally distinct, and can be therapeutically differentiated, from the antagonist activity responsible for irAE.

01 September 2018

CD24 and Fc fusion protein protects SIVmac239-infected Chinese rhesus macaque against progression to AIDS.

Chronic immune activation and systemic inflammation are underlying causes of acquired immunodeficiency syndrome (AIDS). Products of virus replication and microbial translocation, co-infection or opportunistic pathogens, and danger-associated molecular patterns have been reported to contribute to chronic immune activation and inflammation in human immunodeficiency virus type-1/simian immunodeficiency virus (HIV-1/SIV) infection or other disease.

28 April 2018

A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy

It is assumed that anti-CTLA-4 antibodies cause tumor rejection by blocking negative signaling from B7-CTLA-4 interactions. Surprisingly, at concentrations considerably higher than plasma levels achieved by clinically effective dosing, the anti-CTLA-4 antibody Ipilimumab blocks neither B7 trans-endocytosis by CTLA-4 nor CTLA-4 binding to immobilized or cell-associated B7. Consequently, Ipilimumab does not increase B7 on dendritic cells (DCs) from either CTLA4 gene humanized (Ctla4 h/h ) or human CD34+ stem cell-reconstituted NSG™ mice.

01 April 2018

Uncoupling Therapeutic from Immunotherapy-related Adverse Effects for Safer and Effective Anti-CTLA-4 Antibodies in CTLA4 Humanized Mice.

Anti-CTLA-4 monoclonal antibodies (mAbs) confer a cancer immunotherapeutic effect (CITE) but cause severe immunotherapy-related adverse events (irAE). Targeting CTLA-4 has shown remarkable long-term benefit and thus remains a valuable tool for cancer immunotherapy if the irAE can be brought under control. An animal model, which recapitulates clinical irAE and CITE, would be valuable for developing safer CTLA-4-targeting reagents.

01 September 2014

Siglec-G/10 in self-nonself discrimination of innate and adaptive immunity.

Siglec-G/10 is broadly expressed on B cells, dendritic cells and macrophage subsets. It binds strongly to CD24, a small glycosyl-phosphatidylinositol-anchored sialoprotein, in a sialylation-dependent manner. Targeted mutation of Siglecg dramatically elevates the level of natural IgM antibodies and its producer, B1 B cells. Incorporation of Siglec-G ligands to both T-dependent and T-independent immunogens reduces antibody production and induces B-cell tolerance to subsequent antigen challenges.

29 May 2014

Siglec-G-CD24 axis controls the severity of graft-versus-host disease in mice

Activation of sialic-acid-binding immunoglobulin-like lectin-G (Siglec-G) by noninfectious damage-associated molecular patterns controls innate immune responses. However, whether it also regulates T-cell-mediated adaptive immune responses is not known. Graft-versus-host reaction is a robust adaptive immune response caused by allogeneic hematopoietic cell transplantation that have been activated by antigen-presenting cells (APCs) in the context of damaged host tissues following allogeneic hematopoietic cell transplantation

29 July 2012

A hypermorphic SP1-binding CD24 variant associates with risk and progression of multiple sclerosis.

A large number of risk alleles have been identified for multiple sclerosis (MS). However, how genetic variations may affect pathogenesis remains largely unknown for most risk alleles. Through direct sequencing of CD24 promoter region, we identified a cluster of 7 new single nucleotide polymorphisms in the CD24 promoter. A hypermorphic haplotype consisting of 3 SNPs was identified through association studies consisting of 935 control and 764 MS patients (P=0.001, odds ratio 1.3).


About Us

Based in Rockville, Maryland, OncoImmune is a
privately-held, clinical-stage biopharmaceutical
company that is actively engaged in the discovery
and development of biopharmaceuticals for the
treatment of cancer and autoimmune disease.

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