Immunogenic and tolerogenic effects of the chimeric IL-2-diphtheria toxin cytocidal agent Ontak<sup>®</sup>on CD25<sup>+</sup>cells

Lutz, Manfred B.; Baur, Andreas S.; Schuler‐Thurner, Beatrice

doi:10.4161/onci.28223

Cited by 19 publications

(5 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In turn, denileukin diftitox is a fusion protein designed against cells which express the IL-2 receptor. It is used as a drug named Ontak in cutaneous T cell lymphomas (CTCL) expressing CD25 [ 110 , 112 ].…”

Section: Toxinsmentioning

confidence: 99%

Anticancer Activity of Bacterial Proteins and Peptides

2018

View full text Add to dashboard Cite

Despite much progress in the diagnosis and treatment of cancer, tumour diseases constitute one of the main reasons of deaths worldwide. The side effects of chemotherapy and drug resistance of some cancer types belong to the significant current therapeutic problems. Hence, searching for new anticancer substances and medicines are very important. Among them, bacterial proteins and peptides are a promising group of bioactive compounds and potential anticancer drugs. Some of them, including anticancer antibiotics (actinomycin D, bleomycin, doxorubicin, mitomycin C) and diphtheria toxin, are already used in the cancer treatment, while other substances are in clinical trials (e.g., p28, arginine deiminase ADI) or tested in in vitro research. This review shows the current literature data regarding the anticancer activity of proteins and peptides originated from bacteria: antibiotics, bacteriocins, enzymes, nonribosomal peptides (NRPs), toxins and others such as azurin, p28, Entap and Pep27anal2. The special attention was paid to the still poorly understood active substances obtained from the marine sediment bacteria. In total, 37 chemical compounds or groups of compounds with antitumor properties have been described in the present article.

show abstract

Section: Toxinsmentioning

confidence: 99%

Anticancer Activity of Bacterial Proteins and Peptides

2018

View full text Add to dashboard Cite

show abstract

“…The effect of Ontak on immunosuppressive Tregs further enhances anticancer immune responses. Furthermore, CD25 that can be targeted by the IL-2 fusion protein on Ontak is also present on lymphoid tumor cells and dendritic cells effector T cells, making this recombinant protein a great pharmacological intervention strategy (Lutz et al, 2014). However, due to production issues related to bacterial immunotoxin, Ontak was discontinued in 2014 although currently there are several Ontaklike formulations under development that use other bacterial expression systems (Shafiee et al, 2019).…”

Section: Immunogenicitymentioning

confidence: 99%

Cancer Nanomedicine and Immune System—Interactions and Challenges

Ahmad

Idris

Hanaffi

et al. 2021

Front. Nanotechnol.

View full text Add to dashboard Cite

Nanoparticles have tremendous therapeutic potential in the treatment of cancer as they increase drug delivery, attenuate drug toxicity, and protect drugs from rapid clearance. Since Doxil®, the first FDA-approved nanomedicine, several other cancer nanomedicines have been approved and have successfully increased the efficacy over their free drug counterparts. Although their mechanisms of action are well established, their effects towards our immune system, particularly in the tumor microenvironment (TME), still warrant further investigation. Herein, we review the interactions between an approved cancer nanomedicine with TME immunology. We also discuss the challenges that need to be addressed for the full clinical potential of ongoing cancer nanomedicines despite the encouraging preclinical data.

show abstract

“…The same technology also permitted the investigation of strategies targeting IL‐2 to specific cells at the site of action. For example, a fusion molecule of a fragment of diphtheria toxin conjugated to IL‐2 (Ontak ® ) or its improved equivalent E7777 has been investigated for its effectiveness in Treg depletion in clinical trials 106,107 . In this case, when the fusion protein is bound and internalized by cells expressing IL2‐Rα, the diphtheria toxin is released from acidic vesicles into the cytoplasm where it inhibits protein synthesis, leading to subsequent cell death.…”

Section: Il‐2 In Immunotherapymentioning

confidence: 99%

Roles of IL-2 in bridging adaptive and innate immunity, and as a tool for cellular immunotherapy

Bendíčková

Frič

2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

IL‐2 was initially characterized as a T cell growth factor in the 1970s, and has been studied intensively ever since. Decades of research have revealed multiple and diverse roles for this potent cytokine, indicating a unique linking role between adaptive and innate arms of the immune system. Here, we review the literature showing that IL‐2 is expressed in a plethora of cell types across the immune system, where it has indispensable functions in orchestrating cellular interactions and shaping the nature and magnitude of immune responses. Emerging from the basic research that has revealed the molecular mechanisms and the complexity of the biologic actions of IL‐2, several immunotherapeutic approaches have now focused on manipulating the levels of this cytokine in patients. These strategies range from inhibition of IL‐2 to achieve immunosuppression, to the application of IL‐2 as a vaccine adjuvant and in cancer therapies. This review will systematically summarize the major findings in the field and identify key areas requiring further research in order to realize the potential of IL‐2 in the treatment of human diseases.

show abstract

Immunogenic and tolerogenic effects of the chimeric IL-2-diphtheria toxin cytocidal agent Ontak^®on CD25⁺cells

Cited by 19 publications

References 9 publications

Anticancer Activity of Bacterial Proteins and Peptides

Anticancer Activity of Bacterial Proteins and Peptides

Cancer Nanomedicine and Immune System—Interactions and Challenges

Roles of IL-2 in bridging adaptive and innate immunity, and as a tool for cellular immunotherapy

Contact Info

Product

Resources

About

Immunogenic and tolerogenic effects of the chimeric IL-2-diphtheria toxin cytocidal agent Ontak®on CD25+cells

Cited by 19 publications

References 9 publications

Anticancer Activity of Bacterial Proteins and Peptides

Anticancer Activity of Bacterial Proteins and Peptides

Cancer Nanomedicine and Immune System—Interactions and Challenges

Roles of IL-2 in bridging adaptive and innate immunity, and as a tool for cellular immunotherapy

Contact Info

Product

Resources

About

Immunogenic and tolerogenic effects of the chimeric IL-2-diphtheria toxin cytocidal agent Ontak^®on CD25⁺cells