Immunotoxin therapy for hematologic malignancies: where are we heading?

Madhumathi, Jayaprakasam; Sithambaram, Devilakshmi; Sridevi, S.; Verma, Rama Shanker

doi:10.1016/j.drudis.2015.05.002

Cited by 25 publications

(21 citation statements)

References 59 publications

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“…Immunotoxins (ITs) are antibodies, or their fragments, fused to a bacterial, plant, fungal or human apoptotic protein toxin, which become internalised in the target cell and induce cytotoxicity (Madhumathi et al, 2016). The clinical development of ITs has been hindered by several obstacles including low antigen binding specificity of the antibody or antibody fragments and cytotoxicity, immunogenicity and production difficulties.…”

Section: Anti-cd25 Immunotoxinsmentioning

confidence: 99%

The emerging role of anti‐CD25 directed therapies as both immune modulators and targeted agents in cancer

Flynn

Hartley

2017

Br J Haematol

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CD25 (also termed IL2RA) forms one component of the high-affinity heterotrimeric interleukin 2 (IL2) receptor on activated T cells. Its affinity for IL2 and cellular function are tightly regulated and vary in different cell types. The high frequency of CD25 on the surface of many different haematological tumour cells is now well established and, apart from its prognostic significance, CD25 may be present on leukaemic stem cells and enable oncogenic signalling pathways in leukaemic cells. Additionally, high CD25 expression in activated circulating immune cells and Tregs is a factor that has already been exploited by IL2 immunotherapies for treatment of tumours and autoimmune disease. The relative clinical safety and efficacy of administering anti-CD25 radioimmunoconjugates and immunotoxins in various haematological tumour indications has been established and clinical trials of a novel CD25-directed antibody drug conjugate are underway.

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Section: Anti-cd25 Immunotoxinsmentioning

confidence: 99%

The emerging role of anti‐CD25 directed therapies as both immune modulators and targeted agents in cancer

Flynn

Hartley

2017

Br J Haematol

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“…RIT is one of the active research areas in the field of cancer therapy [5]. At present, the two major challenges with this novel treatment modality are toxicity and immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

Novel Antibody Therapeutics Targeting Mesothelin In Solid Tumors

Zhao

Subramanyam

Sarapa³

et al. 2016

CCAND

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BackgroundMonoclonal antibodies have become attractive clinical anti-cancer drugs in the last 3 decades due to their targeting specificity and suitable pharmacokinetic properties. Mesothelin is a tumor-associated antigen with limited expression in normal tissues. It is frequently over-expressed on the cell membrane of a number of epithelial malignancies (e.g. mesothelioma, pancreatic, ovarian, lung, triple negative breast and gastric cancers).MethodsMesothelin is validated as a suitable antibody target for cancer therapy. A number of novel antibody therapeutics targeting mesothelin in development are compared and their mechanisms of action are also discussed. Both basic science and clinical data are provided to give a complete veiw of how an agent is developed from bench to bedside.ResultsNovel antibody therapeutics, including unconjugated monoclonal antibodies, recombinant immunotoxins and antibody-drug conjugates, targeting mesothelin exert anti-tumor activities by different mechanisms of action. Based on the convincing preclinical data generated with these molecules, the antibody therapeutics have been brought into early clinical evaluation where initial promising results were obtained.ConclusionThese antibody therapeutics directed against mesothelin are expected to have different safety profiles, based on their different mechanism of action. Further clinical development will reveal which of these molecules shows the best efficacy and widest therapeutic window and thus is best suited to bring benefit to the patients.

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“…Until now, hundreds of studies have demonstrated the potential for IT application in many different models, both in pre-clinical studies and in clinical trials [9,10,11,12]. Theoretically, ITs could be used to eliminate any unwanted cell that is responsible for a pathological condition.…”

Section: Immunotoxins (Its)mentioning

confidence: 99%

Plant Toxin-Based Immunotoxins for Cancer Therapy: A Short Overview

2016

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Immunotoxins are chimeric proteins obtained by linking a toxin to either an intact antibody or an antibody fragment. Conjugation can be obtained by chemical or genetic engineering, where the latter yields recombinant conjugates. An essential requirement is that the target molecule recognized by the antibody is confined to the cell population to be deleted, or at least that it is not present on stem cells or other cell types essential for the organism’s survival. Hundreds of different studies have demonstrated the potential for applying immunotoxins to many models in pre-clinical studies and in clinical trials. Immunotoxins can be theoretically used to eliminate any unwanted cell responsible for a pathological condition. The best results have been obtained in cancer therapy, especially in hematological malignancies. Among plant toxins, the most frequently employed to generate immunotoxins are ribosome-inactivating proteins, the most common being ricin. This review summarizes the various approaches and results obtained in the last four decades by researchers in the field of plant toxin-based immunotoxins for cancer therapy.

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Immunotoxin therapy for hematologic malignancies: where are we heading?

Cited by 25 publications

References 59 publications

The emerging role of anti‐CD25 directed therapies as both immune modulators and targeted agents in cancer

The emerging role of anti‐CD25 directed therapies as both immune modulators and targeted agents in cancer

Novel Antibody Therapeutics Targeting Mesothelin In Solid Tumors

Plant Toxin-Based Immunotoxins for Cancer Therapy: A Short Overview

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