Immunogenicity and antitumor activity of a liposomal MUC1 peptide-based vaccine

Samuel, John; Budzyński, W; Reddish, Mark A.; Ding, Lei; Zimmermann, G L; Krantz, Mark J.; Koganty, R. Rao; Longenecker, B. M.

doi:10.1002/(sici)1097-0215(19980119)75:2<295::aid-ijc20>3.0.co;2-b

Cited by 70 publications

(42 citation statements)

References 19 publications

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“…Tecemotide (L-BLP25) is a mucin 1 (MUC1) antigen-specific peptide vaccine capable of inducing a T-cell response to MUC1, a glycoprotein that is overexpressed in NSCLC (57). A phase III clinical trial of tecemotide in patients with unresectable stage III NSCLC who completed chemoradiotherapy with confirmed stable disease or objective response did not show a survival benefit for patients receiving the vaccine (58).…”

Section: Antigen-specific Vaccinesmentioning

confidence: 99%

Cancer Immunotherapy: A Future Paradigm Shift in the Treatment of Non–Small Cell Lung Cancer

Anagnostou

Brahmer

2015

Clinical Cancer Research

208

165

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Emerging evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy even for tumors that were historically considered as nonimmunogenic. Immunotherapy is emerging as a major modality in non-small cell lung cancer (NSCLC) treatment focusing on vaccine approaches to elicit specific immune responses and development of inhibitors of the molecular mediators of cancerinduced immunosuppression (immune checkpoints) to boost antitumor immune responses. Amplification of the host response against evolving tumors through vaccination is being investigated in ongoing clinical trials with tumor cell vaccines; however, the clinical efficacy of these agents has been limited. Blocking inhibitory pathways such as the CTL antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) checkpoint pathways with mAbs has generated antitumor immune responses that are transforming cancer therapeutics. PD-1 and programmed cell death ligand 1 (PD-L1) antibodies have shown durable responses in NSCLC, with a favorable safety profile and manageable side effects. The activity of immune checkpoint inhibitors is currently been assessed in treatment-na€ ve patients with PD-L1-positive advanced NSCLC. Combinatorial approaches with other immune checkpoint inhibitors, chemotherapy, or targeted agents are being explored in ongoing clinical trials, and may improve outcome in NSCLC.

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Section: Antigen-specific Vaccinesmentioning

confidence: 99%

Cancer Immunotherapy: A Future Paradigm Shift in the Treatment of Non–Small Cell Lung Cancer

Anagnostou

Brahmer

2015

Clinical Cancer Research

208

165

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“…MUC1 is expressed in the transgenic mice under its own promoter, and the pattern and timing of expression of human and mouse MUC1 show IFN-␥ levels in the 18-wk MET mice were significantly elevated compared with the other time points (p Ͻ 0.05), whereas IL-2 levels were significantly elevated in the 12-wk MET mice (p Ͻ 0.01) and remained elevated until 24 wk of age. The IFN-␥ assay used a sandwich technique as described by Samuel (19). Abs used were R46A2 as capture Ab and second biotinylated Ab XMG1.2.…”

Section: Figurementioning

confidence: 99%

Mice with Spontaneous Pancreatic Cancer Naturally Develop MUC-1-Specific CTLs That Eradicate Tumors When Adoptively Transferred

Mukherjee

Ginardi

Madsen

et al. 2000

The Journal of Immunology

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Pancreatic cancer is a highly aggressive, treatment refractory cancer and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas overexpress altered forms of a tumor-specific Ag, mucin 1 (MUC1; an epithelial mucin glycoprotein), which is a potential target for immunotherapy. We have established a clinically relevant animal model for pancreatic cancer by developing a double transgenic mouse model (called MET) that expresses human MUC1 as self molecule and develops spontaneous tumors of the pancreas. These mice exhibit acinar cell dysplasia at birth, which progresses to microadenomas and acinar cell carcinomas. The tumors express large amounts of underglycosylated MUC1 similar to humans. Tumor-bearing MET mice develop low affinity MUC1-specific CTLs that have no effect on the spontaneously occurring pancreatic tumors in vivo. However, adoptive transfer of these CTLs was able to completely eradicate MUC1-expressing injectable tumors in MUC1 transgenic mice, and these mice developed long-term immunity. These CTLs were MHC class I restricted and recognized peptide epitopes in the immunodominant tandem repeat region of MUC1. The MET mice appropriately mimic the human condition and are an excellent model with which to elucidate the native immune responses that develop during tumor progression and to develop effective antitumor vaccine strategies.

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“…Several cancer vaccines have been proposed for induction or augmentation of anti-tumour immunity, including MUC1 molecules covalently linked to the yeast cell-wall polysaccharide, synthetic peptide encapsulated with monophosphoric lipid A adjuvant, or recombinant vaccinia viruses expressing a modified MUC1 gene (Akagi et al, 1997;Karanikas et al, 1997;Samuel et al, 1998). The escape mechanism of the cancer cells due to the modulation of MUC1 antigenicity observed in this study, however, should be taken into consideration, when targeting the MUC1 mucin for immunotherapy of cancer.…”

Section: Discussionmentioning

confidence: 87%

“…MUC1 is assumed to be a good candidate for adoptive immunotherapy against human cancers (Akagi et al, 1997;Karanikas et al, 1997;Samuel et al, 1998;Acres et al, 2000;Carmon et al, 2000;Wright et al, 2000;Kontani et al, 2000). However, the reaction of autologous CTLs against MUC1 mucin expressed on autologous tumour cells in patients has not been thoroughly characterized.…”

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confidence: 99%

Modulation of MUC1 mucin as an escape mechanism of breast cancer cells from autologous cytotoxic T-lymphocytes

et al. 2001

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Summary MUC1 mucin is known to serve as a target molecule in the killing of breast cancer cells by cytotoxic T-lymphocytes (CTLs). We searched for a possible mechanism allowing tumour cells to escape from autologous CTLs. When the killing of breast cancer cells by autologous lymphocytes was examined in 26 patients with breast cancer, significant tumour cell lysis was observed in 8 patients, whereas virtually no autologous tumour cell lysis was detected in as many as 18 patients. In the patients who showed negligible tumour cell lysis, the autologous tumour cells expressed MUC1-related antigenic epitopes much more weakly than the tumour cells in the patients who exhibited strong cytotoxicity (significant statistically at P < 0.0005-0.0045), suggesting that the unresponsiveness of cancer cells to CTLs observed in these patients was mainly due to loss of MUC1 expression or modulation of its antigenicity. A breast cancer cell line, NZK-1, established from one of the cytotoxicitynegative patients, did not express MUC1 and was resistant to killing by CTLs, while control breast cancer cell lines expressing MUC-1 were readily killed by CTLs. Transfection of NZK-1 cells with MUC1 cDNA induced significant lysis by autologous T-lymphocytes. These results supported the importance of MUC1 mucin in autologous anti-tumour immunity, but suggested that the major escape mechanism of tumour cells from autologous T-lymphocytes is the loss and/or modulation of MUC1 antigenicity on tumour cells, which would limit the effectiveness of possible immunotherapy designed to target the MUC1 mucin.

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Immunogenicity and antitumor activity of a liposomal MUC1 peptide-based vaccine

Cited by 70 publications

References 19 publications

Cancer Immunotherapy: A Future Paradigm Shift in the Treatment of Non–Small Cell Lung Cancer

Cancer Immunotherapy: A Future Paradigm Shift in the Treatment of Non–Small Cell Lung Cancer

Mice with Spontaneous Pancreatic Cancer Naturally Develop MUC-1-Specific CTLs That Eradicate Tumors When Adoptively Transferred

Modulation of MUC1 mucin as an escape mechanism of breast cancer cells from autologous cytotoxic T-lymphocytes

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