Converting Tumoral PD-L1 into a 4-1BB Agonist for Safer and More Effective Cancer Immunotherapy

Li, Zihai; Azar, Joseph; Rubinstein, Mark P.

doi:10.1158/2159-8290.cd-22-0219

Cited by 4 publications

(3 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a key example, understanding CD137 (4-1BB) signaling is of special interest because CD137 is a pursued target in immunotherapy. Experimental agonistic anti-CD137 mAbs are in the clinics ( 71 ), and new CD137-targeting immunotherapeutic agents, including mono-, bi-, and multi-specific antibodies, are being developed ( 11 , 72 ). Furthermore, CAR cassettes often rely on the cytosolic tail of CD137 to transmit costimulatory signals into the transduced T and NK cells ( 26 , 73 ).…”

Section: Discussionmentioning

confidence: 99%

CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects

Glez-Vaz,

Azpilikueta,

Ochoa

et al. 2023

Sci. Adv.

View full text Add to dashboard Cite

CD137 (4-1BB) is a member of the TNFR family that mediates potent T cell costimulatory signals upon ligation by CD137L or agonist monoclonal antibodies (mAbs). CD137 agonists attain immunotherapeutic antitumor effects in cancer mouse models, and multiple agents of this kind are undergoing clinical trials. We show that cIAP1 and cIAP2 are physically associated with the CD137 signaling complex. Moreover, cIAPs are required for CD137 signaling toward the NF-κB and MAPK pathways and for costimulation of human and mouse T lymphocytes. Functional evidence was substantiated with SMAC mimetics that trigger cIAP degradation and by transfecting cIAP dominant-negative variants. Antitumor effects of agonist anti-CD137 mAbs are critically dependent on the integrity of cIAPs in cancer mouse models, and cIAPs are also required for signaling from CARs encompassing CD137’s cytoplasmic tail.

show abstract

Section: Discussionmentioning

confidence: 99%

CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects

Glez-Vaz,

Azpilikueta,

Ochoa

et al. 2023

Sci. Adv.

View full text Add to dashboard Cite

show abstract

“…It can exhibit the conditional 4-1BB agonist activity that relies on the cross-linking with PD-L1. But when playing the role of the PD-L1 inhibitor, it is independent of 4-1BB binding (71,72). Via this special mechanism, GEN1046 represents the enhancement of immune function and anti-tumor activity in both preclinical research and phase I trial (71).…”

Section: Bispecific Antibodiesmentioning

confidence: 99%

Immunotherapy in cervical cancer: From the view of scientometric analysis and clinical trials

Xing

Yasinjan

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

BackgroundCervical cancer is the fourth most cancer and the fourth leading cause of cancer-related deaths in women worldwide. Current treatment for patients with advanced cervical cancer is limited. And in the urgent demand for novel effective therapies both as the first and the second line treatment for these patients, immunotherapy is developing fast and has made some achievements.MethodsThis study incorporated 1,255 topic-related articles and reviews from 1999 to 2022 in the Web of Science Core Collection (WoSCC). The WoS platform, Citespace, and VOS viewer provided the annual distribution of publications and citations, the analysis of researching countries and institutions, references, keywords (co-occurrence analysis, burst analysis, and timeline view analysis), and researching authors, respectively. For clinical trials, 720 trials and 114 trials from ClinicalTrials.gov and ICTRP were retrieved, respectively. And 296 trials were finally incorporated into the analysis.ResultsThe scientometric analysis showed that the study of immunotherapies in cervical cancer developed fast in recent years. Most publications were from the United States, followed by China. Seven of the top 10 co-cited references belong to clinical trials, and five of them were published in recent five years. There are lots of clinical trials us specific treatment patterns, some of which have represented excellent effects.ConclusionsBoth the scientometric analysis of the 1,255 publications and the analysis of clinical trials showed that the field of immunotherapies in cervical cancer developed so fast in recent years. It was found that a lot of clinical trials using various immunotherapies (mainly vaccine therapy, adoptive cell therapy, immune checkpoint blockade, and antibody-drug conjugate) for advanced cervical cancer are currently ongoing or have represented considerable effect. Centered in immunotherapies, immune checkpoint blockades have represented great efficacy and huge potential, especially combined with other therapies such as chemotherapy, targeted therapy, and other immunotherapies.

show abstract

“… 29 Importantly, new CD137 bispecific antibodies targeted to the tumor show evidence for clinical activity. 30 , 31 …”

Section: Introductionmentioning

confidence: 99%

Intratumoral immunotherapy with mRNAs encoding chimeric protein constructs encompassing IL-12, CD137 agonists, and TGF-β antagonists

Cirella,

Bolaños,

Luri-Rey

et al. 2023

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Converting Tumoral PD-L1 into a 4-1BB Agonist for Safer and More Effective Cancer Immunotherapy

Cited by 4 publications

References 9 publications

CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects

CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects

Immunotherapy in cervical cancer: From the view of scientometric analysis and clinical trials

Intratumoral immunotherapy with mRNAs encoding chimeric protein constructs encompassing IL-12, CD137 agonists, and TGF-β antagonists

Contact Info

Product

Resources

About