ArticleCancer immunology, immunotherapy : CII2018
Synergistic cytotoxicity of a prostate cancer-specific immunotoxin in combination with the BH3 mimetic ABT-737.
Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Radiotherapy plus neoadjuvant and concomitant IL-13Rα2-directed immunotoxin therapy for diffuse intrinsic pontine glioma.Communications biology · 2026Article
- Dual-functional Anti-hPSMAApoptosis : an international journal on programmed cell death · 2025Article
- Combination of EGCG and BH3 Mimetic Inhibitor Enhances Apoptosis of MCF-7 and MDA-MB-231 Cancer Cells.Advanced biomedical research · 2025Article
- Review
- Targeted Toxins for the Treatment of Prostate Cancer.Biomedicines · 2021Review
- Engineered Fragments of the PSMA-Specific 5D3 Antibody and Their Functional Characterization.International journal of molecular sciences · 2020Article
- Mechanisms of Resistance to Immunotoxins ContainingBiomolecules · 2020Review
- Article
- Tumor-Specific Induction of the Intrinsic Apoptotic Pathway-A New Therapeutic Option for Advanced Prostate Cancer?Frontiers in oncology · 2019Article
- Bcl-2 Inhibition to Overcome Resistance to Chemo- and Immunotherapy.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
In many tumors, including prostate cancer, anti-apoptotic members of the Bcl-2 family are overexpressed and cause cell death resistance, which is a typical hallmark of cancer. Different therapeutic approaches, therefore, aim to restore the death mechanisms for enhanced apoptosis. Our recombinant immunotoxin D7(VL-VH)-PE40 is composed of the scFv D7(VL-VH) against the prostate-specific membrane antigen (PSMA) on the surface of prostate cancer cells and of the cytotoxic domain of the bacterial toxin Pseudomonas Exotoxin A (PE40). Since Pseudomonas Exotoxin A-based immunotoxins are known to preferentially inhibit the expression of the anti-apoptotic protein Mcl-1, the rationale was to test our immunotoxin in combination with the BH3 mimetic ABT-737, which specifically inhibits Bcl-2, Bcl-xl, and Bcl-w for enhanced induction of apoptosis in prostate cancer cells. The immunotoxin showed high and specific binding and cytotoxicity against PSMA expressing prostate cancer cells marked by a direct inhibition of Mcl-1. The combination of the immunotoxin with a subtoxic concentration of ABT-737 caused additive or even synergistic effects, which were based on an enhanced apoptosis induction as detected by poly(ADP-ribose) polymerase (PARP) and Caspase-3 cleavage in Western blot. Our study shows that the combination therapy of immunotoxin plus ABT-737 is a promising approach for the future treatment of advanced prostate cancer to improve therapeutic efficacy and to reduce adverse side effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.