Last update 19 Sep 2024

GDF

Last update 19 Sep 2024

Basic Info

Synonyms

GD, GdA, GdF

+ [16]

Introduction

Glycoprotein that regulates critical steps during fertilization and also has immunomonomodulatory effects. Four glycoforms, namely glycodelin-S, -A, -F and -C have been identified in reproductive tissues that differ in glycosylation and biological activity. Glycodelin-A has contraceptive and immunosuppressive activities (PubMed:9918684, PubMed:7531163). Glycodelin-C stimulates binding of spermatozoa to the zona pellucida (PubMed:17192260). Glycodelin-F inhibits spermatozoa-zona pellucida binding and significantly suppresses progesterone-induced acrosome reaction of spermatozoa (PubMed:12672671). Glycodelin-S in seminal plasma maintains the uncapacitated state of human spermatozoa (PubMed:15883155).

Drugs associated with GDF

HS235

Target

GDF x activin receptor

Mechanism

GDF modulators [+1]

Active Org.

35Pharma, Inc.

Originator Org.

35Pharma, Inc.

Active Indication

Obesity

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ACE-06X

Target

GDF

Mechanism

GDF modulators

Active Org.-

Originator Org.

Acceleron Pharma, Inc.

Active Indication-

Inactive Indication

Metabolic Diseases

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GDF

100 Translational Medicine associated with GDF

0 Patents (Medical) associated with GDF

1,202

Literatures (Medical) associated with GDF

01 Oct 2024·Translational Research

The pregnancy-associated protein glycodelin as a potential sex-specific target for resistance to immunotherapy in non-small cell lung cancer

Article

Author: Muley, Thomas ; Meister, Michael ; Christopoulos, Petros ; Klingmüller, Ursula ; Goldmann, Torsten ; Allgäuer, Michael ; Marwitz, Sebastian ; Richtmann, Sarah ; Winter, Hauke ; Schneider, Marc A ; Koistinen, Hannu ; Kazdal, Daniel ; Thomas, Michael

Lung cancer has been shown to be targetable by novel immunotherapies which reactivate the immune system and enable tumor cell killing. However, treatment failure and resistance to these therapies is common. Consideration of sex as a factor influencing therapy resistance is still rare. We hypothesize that the success of the treatment is impaired by the presence of the immunosuppressive pregnancy-associated glycoprotein glycodelin that is expressed in patients with non-small-cell lung cancer (NSCLC). We demonstrate that the glycan pattern of NSCLC-derived glycodelin detected by a lectin-based enrichment assay highly resembles amniotic fluid-derived glycodelin A, which is known to have immunosuppressive properties. NSCLC-derived glycodelin interacts with immune cells in vitro and regulates the expression of genes associated with inflammatory and tumor microenvironment pathways. In tumor microarray samples of patients, high glycodelin staining in tumor areas results in an impaired overall survival of female patients. Moreover, glycodelin colocalizes to tumor infiltrating CD8+ T cells and pro-tumorigenic M2 macrophages. High serum concentrations of glycodelin prior to immunotherapy are associated with a poor progression-free survival (p < 0.001) of female patients receiving PD-(L)1 inhibitors. In summary, our findings suggest that glycodelin not only is a promising immunological biomarker for early identification of female patients that do not benefit from the costly immunotherapy, but also represents a promising immunotherapeutic target in NSCLC to improve therapeutic options in lung cancer.

20 Aug 2024·ACS Nano

Liposomes with Low Levels of Grafted Poly(ethylene glycol) Remain Susceptible to Destabilization by Anti-Poly(ethylene glycol) Antibodies

Article

Author: Barenholz, Yechezkel ; Tran, Trieu Thi My ; Yang, Shih-Hung ; Turjeman, Keren ; Chen, Even ; Cheng, Tian-Lu ; Chen, Bing-Mae ; Lin, Yi-Chen ; Roffler, Steve R.

Binding of anti-PEG antibodies to poly(ethylene glycol) (PEG) on the surface of PEGylated liposomal doxorubicin (PLD) in vitro and in rats can activate complement and cause the rapid release of doxorubicin from the liposome interior. Here, we find that irinotecan liposomes (IL) and L-PLD, which have 16-fold lower levels of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-PEG₂₀₀₀ in their liposome membrane as compared to PLD, generate less complement activation but remain sensitive to destabilization and drug release by anti-PEG antibodies. Complement activation and liposome destabilization correlated with the theoretically estimated number of antibody molecules bound per liposome. Drug release from liposomes proceeded through the alternative complement pathway but was accelerated by the classical complement pathway. In contrast to PLD destabilization by anti-PEG immunoglobulin G (IgG), which proceeded by the insertion of membrane attack complexes in the lipid bilayer of otherwise intact PLD, anti-PEG IgG promoted the fusion of L-PLD, and IL to form unilamellar and oligo-vesicular liposomes. Anti-PEG immunoglobulin M (IgM) induced drug release from all liposomes (PLD, L-PLD, and IL) via the formation of unilamellar and oligo-vesicular liposomes. Anti-PEG IgG destabilized both PLD and L-PLD in rats, indicating that the reduction of PEG levels on liposomes is not an effective approach to prevent liposome destabilization by anti-PEG antibodies.

13 Aug 2024·ACS Omega

Impact of the Hydrophilicity of Poly(sarcosine) on Poly(ethylene glycol) (PEG) for the Suppression of Anti-PEG Antibody Binding

Article

Author: Shiraishi, Kouichi ; Yokoyama, Masayuki ; Maiti, Debabrata

A method of poly(ethylene glycol) (PEG) conjugation is known as PEGylation, which has been employed to deliver therapeutic drugs, proteins, or nanoparticles by considering the intrinsic non- or very low immunogenic property of PEG. However, PEG has its weaknesses, and one major concern is the potential immunogenicity of PEGylated proteins. Because of its hydrophilicity, poly(sarcosine) (P(Sar)) may be an attractive-and superior-substitute for PEG. In the present study, we designed a double hydrophilic diblock copolymer, methoxy-PEG-b-P(Sar) _m (m = 5-55) (mPEG-P(Sar) _m ), and synthesized a triblock copolymer with hydrophobic poly(l-isoleucine) (P(Ile)). We validated that double hydrophilic mPEG-P(Sar) block copolymers suppressed the specific binding of three monoclonal anti-PEG antibodies (anti-PEG mAbs) to PEG. The results of our indirect ELISAs indicate that P(Sar) significantly helps to reduce the binding of anti-PEG mAbs to PEG. Importantly, the steady suppression of this binding was made possible, in part, thanks to the maximum number of sarcosine units in the triblock copolymer, as evidenced by sandwich ELISA and biolayer interferometry assay (BLI): the intrinsic hydrophilicity of P(Sar) had a clear supportive effect on PEG. Finally, because we used P(Ile) as a hydrophobic block, PEG-P(Sar) might be an attractive alternative to PEG in the search for protein shields that minimize the immunogenicity of PEGylated proteins.

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