In vivo anti-MUC1+ tumor activity and sequences of high-affinity anti-MUC1-SEA antibodies

Pichinuk, Edward; Chalik, Michael; Benhar, Itai; Ginat-Koton, Ravit; Ziv, Ravit; Smorodinsky, Nechama I.; Haran, Gabi; Garbar, Christian; Bensussan, Armand; Meeker, Alan K.; Guillaume, Thierry; Rubinstein, D. B.; Wreschner, Daniel H.

doi:10.1007/s00262-020-02547-2

Cited by 14 publications

(8 citation statements)

References 42 publications

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“…Thus, inhibition of MUC1 activities could likely be an advantageous strategy in cancer therapy [ 24 ]. Moreover, its high expression, differential distribution pattern relative to normal cells, and altered architecture in malignant tissues made this molecule a top molecular target in anti-cancer treatment [ 13 , 14 , 25 , 26 , 27 ]. Antibodies have been confirmed to be compelling additions to therapy for many types of cancer [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Action of Anti-MUC1 Monoclonal Antibody and Pyrazole-Platinum(II) Complexes Reveals Higher Effectiveness towards Apoptotic Response in Comparison with Monotherapy in AGS Gastric Cancer Cells

et al. 2021

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MUC1 mucin is a transmembrane glycoprotein aberrantly overexpressed and underglycosylated in most epithelium origin cancers. Combining chemotherapeutics with monoclonal antibodies toward cancer-related antigens is one of the new strategies in cancer therapies. In this study, we assessed the effectiveness of 10 μM cisplatin (cisPt), two pyrazole-platinum(II) complexes (PtPz4 and PtPz6), and 5 μg/mL anti-MUC1 used as monotherapy, as well as cisplatin and its derivatives combined with mAb on apoptotic response and specific cancer-related sugar antigens in AGS gastric cancer cells. Flow cytometry, RT-PCR, Western blotting, and ELISA tests were applied to determine the influence of examined compounds on analyzed factors. PtPz6 combined with anti-MUC1 revealed the strongest apoptotic response compared to control and monotherapy. The combined action of both cisPt derivatives and anti-MUC1 was more effective than monotherapy in relation to Bad, Bcl-xL, Bcl-2, caspase-9, caspase-3, as well as pro- and cleaved caspase-3 protein, and T, sialyl Tn sugar antigens in cell lysates, and Tn, T, sialyl Tn, sialyl T antigens in culture medium. Additionally, PtPz4 administrated with mAb was revealed to be more potent than used alone with regard to Bax protein and Bid expression, and PtPz6 used in complex with anti-MUC1 revealed more efficient action towards Akt and sialyl T antigen expression. These data indicate the rationality of the potential application of combined treatment of anti-MUC1 and cisPt derivatives in gastric cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Combined Action of Anti-MUC1 Monoclonal Antibody and Pyrazole-Platinum(II) Complexes Reveals Higher Effectiveness towards Apoptotic Response in Comparison with Monotherapy in AGS Gastric Cancer Cells

et al. 2021

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“…MUC1 is reported to be up to 10 times higher in many cancers in comparison with normal cells. Moreover, it is aberrantly glycosylated and specifically distributed over the whole cell surface and within the cytoplasm, nuclei, and mitochondria of malignant cells [ 4 , 7 , 31 , 32 ]. Thus, MUC1 fulfills all the requirements to be targeted molecule in mAb-based anti-cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

Anti-cancer effects of pyrazole-platinum(II) complexes combined with anti-MUC1 monoclonal antibody versus monotherapy in DLD-1 and HT-29 colon cancer cells

Supruniuk

Czarnomysy

Muszyńska

et al. 2022

Translational Oncology

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Highlights Bcl-2 was suppressed more effectively by combined treatment in DLD-1 and HT-29 cells. Casp-9,-3 were stimulated more effectively by combined treatment in both cell lines. TACAs were supressed more effectively by combined treatment in both cell lines. Anti-MUC1 combined with PtPz4, PtPz6 or cisPt is more effective than monotherapy.

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“…Of note, GO-201, a synthetic peptide that inhibits MUC1-C oligomerization displays antiprostate cancer activity in preclinical studies (81). Additionally, upon linkage to ZZ-PE38, the Fc-binding ZZ domain of protein A fused to Pseudomonas exotoxin (82), a humanized mAb DMB5F3 potently killed MUC1 + cancer cells (83). DMB5F3 recognizes the SEA domain shared between MUC1-N and MUC1-C (83).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, upon linkage to ZZ-PE38, the Fc-binding ZZ domain of protein A fused to Pseudomonas exotoxin (82), a humanized mAb DMB5F3 potently killed MUC1 + cancer cells (83). DMB5F3 recognizes the SEA domain shared between MUC1-N and MUC1-C (83). The therapeutic utility of GO-201 and DMB5F3-ZZ-PE38 in treating prostate cancer should be investigated either alone or together with the current MUC1 vaccines.…”

Section: Discussionmentioning

confidence: 99%

MUCIN 1 in Prostate Cancer

Kapoor

Lin

et al. 2021

Prostate Cancer

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Despite extensive research efforts in prostate cancer for the last several decades, the disease remains a leading cause of cancer death in men in the developed world. A typical feature of prostate cancer initiation and progression is the landscape of genetic alterations, which changes the expression patterns of numerous molecules in prostate epithelial cells, where the disease originates. These aberrantly expressed proteins are tumor-associated antigens. Their uniqueness in tumors offers an avenue not only in advancing our understanding of prostate cancer but also in the search for better diagnostic and therapeutic tools. Mucin 1 is one of the most well-characterized tumor-associated antigens. The protein is overexpressed and aberrantly glycosylated following prostate cancer development, and influences certain disease factors including disease initiation, metastasis, and resistance to therapy. Mucin 1 possesses value as a biomarker in predicting prostate cancer prognosis and has been studied as a therapeutic target. This chapter provides an overview of the impact of Mucin 1 on prostate cancer and its clinical values.

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In vivo anti-MUC1+ tumor activity and sequences of high-affinity anti-MUC1-SEA antibodies

Cited by 14 publications

References 42 publications

Combined Action of Anti-MUC1 Monoclonal Antibody and Pyrazole-Platinum(II) Complexes Reveals Higher Effectiveness towards Apoptotic Response in Comparison with Monotherapy in AGS Gastric Cancer Cells

Combined Action of Anti-MUC1 Monoclonal Antibody and Pyrazole-Platinum(II) Complexes Reveals Higher Effectiveness towards Apoptotic Response in Comparison with Monotherapy in AGS Gastric Cancer Cells

Anti-cancer effects of pyrazole-platinum(II) complexes combined with anti-MUC1 monoclonal antibody versus monotherapy in DLD-1 and HT-29 colon cancer cells

MUCIN 1 in Prostate Cancer

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