Vestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers

Bradley, Sherille D.; Talukder, Amjad H.; Lai, Ivy; Davis, Rebecca K.; Alvarez, Hector A.; Tiriac, Hervé; Zhang, Minying; Chiu, Yulun; Melendez, Brenda; Jackson, Kyle R.; Katailiha, Arjun; Sonnemann, Heather M.; Li, Fenge; Kang, Ya’an; Qiao, Na; Pan, Bih Fang; Lorenzi, Philip L.; Hurd, Mark W.; Mittendorf, Elizabeth A.; Peterson, Christine B.; Javle, Milind; Bristow, Christopher A.; Kim, Michael; Tuveson, David A.; Hawke, David H.; Kopetz, Scott; Wolff, Robert A.; Hwu, Patrick; Maitra, Anirban; Roszik, Jason; Yee, Cassian; Lizée, Gregory

doi:10.1038/s41467-020-19141-w

Cited by 20 publications

(18 citation statements)

References 65 publications

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“…A similar trend was observed in the HSILs (Data not shown). To the best of our knowledge, PLAC1 is expressed at low levels in normal cervical cells ( 23 ). Protein expression levels of PLAC1 in CC lines, including CaSki, MS751, C-33A and HeLa, were notably upregulated ( Fig.…”

Section: Resultsmentioning

confidence: 99%

PLAC1 is an independent predictor of poor survival, and promotes cell proliferation and invasion in cervical cancer

Chen

Sheng

et al. 2021

Mol Med Rep

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Placenta-specific protein 1 (PLAC1) is inversely associated with survival in several types of cancer. However, whether PLAC1 is involved in the progression of cervical cancer (CC) remains to be elucidated. Therefore, the present study aimed to evaluate the prognostic role of PLAC1 in CC by determining the relationship between clinicopathological factors, PLAC1 gene expression and survival prognosis using univariate and multivariate Cox proportional-hazards regression analyses. Similarly, Kaplan-Meier curves were evaluated with the log-rank test. Subsequently, gene set enrichment analysis was performed to compare the highand low-PLAC1 expression phenotypes. Functional studies were further conducted in PLAC1-overexpressing HeLa cells and PLAC1-silenced MS751 cells, and western blotting was performed to determine whether PLAC1 promoted CC progression via epithelial-mesenchymal transition (EMT). The findings demonstrated that high expression of PLAC1 was associated with American Joint Committee on Cancer metastasis pathological score and suggested a poor overall survival. 'mTOR complex 1 signaling', 'interferon α response' and 'hypoxia' were differentially enriched in the high-PLAC1 phenotype. Furthermore, PLAC1 promoted the invasion of CC cells in vitro. E-cadherin expression was decreased in the PLAC1-overexpressing cells, accompanied by increased expression of the mesenchymal markers, Vimentin, MMP2 and Slug, and the opposite effects were observed in PLAC1-silenced cells. Taken together, the present results indicated that high expression of PLAC1 was associated with poor survival and PLAC1 promoted metastasis via EMT in CC.

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Section: Resultsmentioning

confidence: 99%

PLAC1 is an independent predictor of poor survival, and promotes cell proliferation and invasion in cervical cancer

Chen

Sheng

et al. 2021

Mol Med Rep

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“…Using this method, we have identified and validated peptides associated with the melanoma differentiation antigen SLC45A2 as shared melanoma-associated tumor targets and have generated TCRs recognizing these peptides. Similarly, we identified VGLL1 as a shared pancreatic and basal breast cancer tumorassociated antigen, for which TCRs showing antitumor activity have been isolated [27][28][29]. TCR-T cell clinical trials targeting these two TAAs are currently in the design stages.…”

Section: Methods For Identifying Tumor-associated Antigensmentioning

confidence: 94%

“…With the recent advances in next-generation sequencing technology, particularly single-cell DNA sequencing, transcriptome sequencing, and well-developed in vitro validation approaches, including ELISPOT assay and tetramer staining, it is possible that TCR-T immunotherapy targeting personalized neoantigens will become a feasible approach for cancer treatment in the years to come. Furthermore, new categories of emerging TAAs such as cancer-placenta antigens may also constitute viable shared targets for future TCR-T development [27].…”

Section: Discovery Of New Targetsmentioning

confidence: 99%

Evolution of CD8+ T Cell Receptor (TCR) Engineered Therapies for the Treatment of Cancer

Sun

Sonnemann

et al. 2021

Cells

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Engineered T cell receptor T (TCR-T) cell therapy has facilitated the generation of increasingly reliable tumor antigen-specific adaptable cellular products for the treatment of human cancer. TCR-T cell therapies were initially focused on targeting shared tumor-associated peptide targets, including melanoma differentiation and cancer-testis antigens. With recent technological developments, it has become feasible to target neoantigens derived from tumor somatic mutations, which represents a highly personalized therapy, since most neoantigens are patient-specific and are rarely shared between patients. TCR-T therapies have been tested for clinical efficacy in treating solid tumors in many preclinical studies and clinical trials all over the world. However, the efficacy of TCR-T therapy for the treatment of solid tumors has been limited by a number of factors, including low TCR avidity, off-target toxicities, and target antigen loss leading to tumor escape. In this review, we discuss the process of deriving tumor antigen-specific TCRs, including the identification of appropriate tumor antigen targets, expansion of antigen-specific T cells, and TCR cloning and validation, including techniques and tools for TCR-T cell vector construction and expression. We highlight the achievements of recent clinical trials of engineered TCR-T cell therapies and discuss the current challenges and potential solutions for improving their safety and efficacy, insights that may help guide future TCR-T studies in cancer.

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“…Class-I binding peptide isolation and identification via immune-precipitation (IP) and tandem mass spectrometry (MS) methods are referenced from prior study (36). Briefly, about 300 to 500 million cells engineered to express the SARS-CoV-2 MGP or NSP13 gene were homogenized in cold NP40 lysis buffer supplemented with protease inhibitor cocktail (Roche, CA, USA).…”

Section: Hla Class-i Binding Peptide Identification Hlamentioning

confidence: 99%

Immunogenic SARS-CoV2 Epitopes Defined by Mass Spectrometry

Pan

Chiu

Huang

et al. 2021

Preprint

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SARS-CoV-2 infections elicit both humoral and cellular immune responses. For the prevention and treatment of COVID19, the disease caused by SARS-CoV-2, T cell responses are important in mediating recovery and immune-protection. The identification of immunogenic epitopes that can elicit a meaningful T cell response can be elusive. Traditionally, this has been achieved using sophisticated in silico methods to predict putative epitopes; however, our previous studies find that immunodominant SARS-CoV-2 peptides defined by such in silico methods often fail to elicit T cell responses recognizing SARS-CoV-2. We postulated that immunogenic epitopes for SARS-CoV-2 are best defined by directly analyzing peptides eluted from the peptide-MHC complex and then validating immunogenicity empirically by determining if such peptides can elicit T cells recognizing SARS-CoV-2 antigen-expressing cells. Using a tandem mass spectrometry approach, we identified epitopes of SARS-CoV-2 derived not only from structural but also non-structural genes in regions highly conserved among SARS-CoV-2 strains including recently recognized variants. We report here, for the first time, several novel SARS-CoV-2 epitopes from membrane glycol-protein (MGP) and non-structure protein-13 (NSP13) defined by mass-spectrometric analysis of MHC-eluted peptides, provide empiric evidence for their immunogenicity to induce T cell response.

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Vestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers

Cited by 20 publications

References 65 publications

PLAC1 is an independent predictor of poor survival, and promotes cell proliferation and invasion in cervical cancer

PLAC1 is an independent predictor of poor survival, and promotes cell proliferation and invasion in cervical cancer

Evolution of CD8+ T Cell Receptor (TCR) Engineered Therapies for the Treatment of Cancer

Immunogenic SARS-CoV2 Epitopes Defined by Mass Spectrometry

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