Placenta-specific1 (PLAC1) is a potential target for antibody-drug conjugate-based prostate cancer immunotherapy

Nejadmoghaddam, Mohammad-Reza; Zarnani, Amir‐Hassan; Ghahremanzadeh, Ramin; Ghods, Roya; Mahmoudian, Jafar; Yousefi, Maryam; Nazari, Mahboobeh; Ghahremani, Mohammad Hossein; Abolhasani, Maryam; Anissian, Ali; Dinarvand, Rassoul

doi:10.1038/s41598-017-13682-9

Cited by 32 publications

(46 citation statements)

References 38 publications

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“…Among these, an example worth mentioning are PLAC1 and syncytins, which are placenta-specific genes [ 11 ]. PLAC1 is re-expressed in prostate, breast and ovary cancer and is a potential target for antibody–drug conjugate-based prostate cancer immunotherapy [ 106 ]. Syncytins, a family of placenta-specific genes evolved from retroelements and involved in placenta cell fusion are also highly expressed in breast and other cancers, where they contribute to cancer cell fusion with endothelium, a process that can be targeted by syncytin inhibiting peptides [ 107 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the links between cancer and placenta development

et al. 2018

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The development of metastatic cancer is a multistage process, which often requires decades to complete. Impairments in DNA damage control and DNA repair in cancer cell precursors generate genetically heterogeneous cell populations. However, despite heterogeneity most solid cancers have stereotypical behaviours, including invasiveness and suppression of immune responses that can be unleashed with immunotherapy targeting lymphocyte checkpoints. The mechanisms leading to the acquisition of stereotypical properties remain poorly understood. Reactivation of embryonic development processes in cells with unstable genomes might contribute to tumour expansion and metastasis formation. However, it is unclear whether these events are linked to immune response modulation. Tumours and embryos have non-self-components and need to avoid immune responses in their microenvironment. In mammalian embryos, neo-antigens are of paternal origin, while in tumour cells DNA mismatch repair and replication defects generate them. Inactivation of the maternal immune response towards the embryo, which occurs at the placental–maternal interface, is key to ensuring embryonic development. This regulation is accomplished by the trophoblast, which mimics several malignant cell features, including the ability to invade normal tissues and to avoid host immune responses, often adopting the same cancer immunoediting strategies. A better understanding as to whether and how genotoxic stress promotes cancer development through reactivation of programmes occurring during early stages of mammalian placentation could help to clarify resistance to drugs targeting immune checkpoint and DNA damage responses and to develop new therapeutic strategies to eradicate cancer.

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Section: Discussionmentioning

confidence: 99%

Exploring the links between cancer and placenta development

et al. 2018

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“…After mixing the AF647 labeled anti-HER2 mAb-MMAE ADC (red color) with the HER2 + BT474 cells (blue color), the ADC bound to cell surface within 20 min. Then the ADC is quickly internalized, which is triggered by the receptor-mediated endocytosis [ 26 ], properly localized at late endosome (green color) for lysozyme degradation within 40 min [ 27 ], and continuously accumulated intracellularly within 60 min [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Bioprocess development of antibody-drug conjugate production for cancer treatment

Goh

et al. 2018

PLoS ONE

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Antibody-drug conjugate (ADC) is a class of targeted cancer therapies that combine the advantages of monoclonal antibody (mAb)’s specific targeting and chemotherapy’s potent cytotoxicity. The therapeutic effect of ADC is significantly affected by its bioproduction process. This study aims to develop an effective ADC production process using anti-HER2 mAb-drug as a model therapeutic. First, a high titer (>2 g/L) of mAb was produced by Chinese hamster ovary cells from fed-batch cell culture. Both live-cell confocal microscopy imaging and flow cytometry analysis demonstrated that the produced mAb and ADC had strong and specific binding to HER2+ cell line BT474. Second, various conjugation conditions of mAb and drug, including linker selection, ratio of drug and mAb, and conjugation approaches, were investigated to improve the production yield and product quality. Finally, the ADC structure and biological quality were evaluated by SDS-PAGE and anti-breast cancer toxicity study, respectively. The ADC with integral molecular structure and high cytotoxicity (IC50 of 1.95 nM) was produced using the optimized production process. The robust bioproduction process could guide the development of ADC-based biopharmaceuticals.

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“…Nejadmoghaddam et al evaluated PLAC-1 (placenta specific-1) as another potential target for antibody-drug conjugate therapy against PCa in mouse models. 106 …”

Section: Antibody-based Therapymentioning

confidence: 99%

Immunotherapy in prostate cancer: current state and future perspectives

Handa¹,

Hans

Goel

et al. 2020

Therapeutic Advances in Urology

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Metastatic castrate resistant prostate cancer (PCa) remains an incurable entity. In the era of immunotherapy, the complex PCa microenvironment poses a unique challenge to the successful application of this class of agents. However, in the last decade, a tremendous effort has been made to explore this field of therapeutics. In this review, the physiology of the cancer immunity cycle is highlighted in the context of the prostate tumor microenvironment, and the current evidence for use of various classes of immunotherapy agents including vaccines (dendritic cell based, viral vector based and DNA/mRNA based), immune checkpoint inhibitors, Chimeric antigen receptor T cell therapy, antibody-mediated radioimmunotherapy, antibody drug conjugates, and bispecific antibodies, is consolidated. Finally, the future directions for combinatorial approaches to combat PCa are discussed.

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Placenta-specific1 (PLAC1) is a potential target for antibody-drug conjugate-based prostate cancer immunotherapy

Cited by 32 publications

References 38 publications

Exploring the links between cancer and placenta development

Exploring the links between cancer and placenta development

Bioprocess development of antibody-drug conjugate production for cancer treatment

Immunotherapy in prostate cancer: current state and future perspectives

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