Mesothelin targeted cancer immunotherapy

Hassan, Raffit; Ho, Mitchell

doi:10.1016/j.ejca.2007.08.028

Cited by 292 publications

(266 citation statements)

References 39 publications

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“…Human testing generated encouraging results and Phase I trial are under way [94,95]. A good recent review on that matter was published recently [96].…”

Section: Therapeutic Uses Of Membrane Bound Mesothelinmentioning

confidence: 99%

Clinical utility of diagnostic markers for malignant pleural mesothelioma

Grigoriu

Grigoriu²,

Chahine

et al. 2016

Monaldi Arch Chest Dis

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Malignant mesothelioma has a very dismal prognosis with very few patients surviving one year after diagnosis. Early multimodal treatment, however, is expected to improve the outcome. Today, there is a strong need to have disease markers which could be used for screening, diagnosing, and/or monitoring tumour response to treatment. Old markers such as hyaluronic acid, various cytokeratin fragments (CYFRA 21.1, TPA) and other cancer antigens (CA 15.3, CA 125 or CA 19.9 or CEA) are not sensitive or specific enough and cannot be used in practice. More recently new molecules, such as soluble mesothelin and osteopontin, have been proposed for diagnostic purposes. Soluble mesothelin has a good specificity but has a suboptimal sensitivity being negative in all sarcomatoid and in up to one half of epithelioid mesothelioma. On the contrary osteopontin has an inadequate specificity. Combining different markers together does not lead to an improvement in diagnostic accuracy. Neither marker can be used for screening purposes, the main limitation being the very low incidence of the disease in the at-risk, asbestos exposed population. Mesothelin is also a promising marker for monitoring response to treatment but published data is still insufficient to make recommendations. There is still a strong need for research is this area both in order to discover new markers as well as to correct the positioning of each existing molecule (alone or in combination) is the evaluation of the patients with a mesothelioma.

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“…Human testing generated encouraging results and Phase I trial are under way [94,95]. A good recent review on that matter was published recently [96].…”

Section: Therapeutic Uses Of Membrane Bound Mesothelinmentioning

confidence: 99%

Clinical utility of diagnostic markers for malignant pleural mesothelioma

Grigoriu

Grigoriu²,

Chahine

et al. 2016

Monaldi Arch Chest Dis

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“…Moreover, mesothelin expression is found in 50% of lung adenocarcinomas, 60% of gastric cancers, and 67% of triple-negative breast cancers (1)(2)(3)(4)(5)(6)(7)(8). Expression in normal tissues is mainly restricted to the single cell layers lining the pleura, pericardium, and peritoneum (1,9).…”

Section: Introductionmentioning

confidence: 99%

Anetumab Ravtansine: A Novel Mesothelin-Targeting Antibody–Drug Conjugate Cures Tumors with Heterogeneous Target Expression Favored by Bystander Effect

Golfier

Kopitz

Kahnert

et al. 2014

Molecular Cancer Therapeutics

199

173

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Mesothelin is a tumor differentiation antigen frequently overexpressed in tumors such as mesothelioma, ovarian, pancreatic, and lung adenocarcinomas while showing limited expression in nonmalignant tissues. Mesothelin is therefore an attractive target for cancer therapy using antibody-drug conjugates (ADC). This study describes the detailed characterization of anetumab ravtansine, here referred to as BAY 94-9343, a novel ADC consisting of a human anti-mesothelin antibody conjugated to the maytansinoid tubulin inhibitor DM4 via a disulfide-containing linker. Binding properties of the anti-mesothelin antibody were analyzed using surface plasmon resonance, immunohistochemistry, flow cytometry, and fluorescence microscopy. Effects of BAY 94-9343 on cell proliferation were first studied in vitro and subsequently in vivo using subcutaneous, orthotopic, and patient-derived xenograft tumor models. The antibody binds to human mesothelin with high affinity and selectivity, thereby inducing efficient antigen internalization. In vitro, BAY 94-9343 demonstrated potent and selective cytotoxicity of mesothelin-expressing cells with an IC 50 of 0.72 nmol/L, without affecting mesothelin-negative or nonproliferating cells. In vivo, BAY 94-9343 localized specifically to mesothelin-positive tumors and inhibited tumor growth in both subcutaneous and orthotopic xenograft models. In addition, BAY 94-9343 was able to induce a bystander effect on neighboring mesothelin-negative tumor cells. Antitumor efficacy of BAY 94-9343 correlated with the amount of mesothelin expressed and was generally superior to that of standard-of-care regimen resulting in complete tumor eradication in most of the models. BAY 94-9343 is a selective and highly potent ADC, and our data support its development for the treatment of patients with mesothelin-expressing tumors. Mol Cancer Ther; 13(6); 1537-48. Ó2014 AACR.

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“…11,14 Antimesothelin agents, namely recombinant immunotoxin, the chimeric antimesothelin mAb and the Listeria monocytogenesmesothelin vaccine are used in clinical practice or about to enter in clinical trials. 15 Selection of an appropriate TAA is crucial for the design of vaccines and an essential prerequisite for induction of a strong immune response. The limited number of PDAC-associated antigens that can be candidates for vaccines, and the persistent lack of effectiveness of vaccine trials have prompted our search for new TAA.…”

Section: Uiccmentioning

confidence: 99%

An integrated humoral and cellular response is elicited in pancreatic cancer by α‐enolase, a novel pancreatic ductal adenocarcinoma‐associated antigen

Cappello¹,

Tomaino²,

Chiarle³

et al. 2009

Intl Journal of Cancer

107

125

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Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a very poor 5-year survival rate. a-Enolase is a glycolytic enzyme that also acts as a surface plasminogen receptor. We find that it is overexpressed in PDAC and present on the cell surface of PDAC cell lines. The clinical correlation of its expression with tumor status has been reported for lung and hepatocellular carcinoma. We have previously demonstrated that sera from PDAC patients contain IgG autoantibodies to a-enolase. The present work was intended to assess the ability of a-enolase to induce antigen-specific T cell responses. We show that a-enolase-pulsed dendritic cells (DC) specifically stimulate healthy autologous T cells to proliferate, secrete IFN-c and lyse PDAC cells but not normal cells. In vivo, a-enolase-specific T cells inhibited the growth of PDAC cells in immunodeficient mice. In 8 out of 12 PDAC patients with circulating IgG to a-enolase, the existence of a-enolase-specific T cells was also demonstrated. Taken as a whole, these results indicate that a-enolase elicits a PDAC-specific, integrated humoral and cellular response. It is thus a promising and clinically relevant molecular target candidate for immunotherapeutic approaches as new adjuvants to conventional treatments in pancreatic cancer. ' 2009 UICC

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Mesothelin targeted cancer immunotherapy

Cited by 292 publications

References 39 publications

Clinical utility of diagnostic markers for malignant pleural mesothelioma

Clinical utility of diagnostic markers for malignant pleural mesothelioma

Anetumab Ravtansine: A Novel Mesothelin-Targeting Antibody–Drug Conjugate Cures Tumors with Heterogeneous Target Expression Favored by Bystander Effect

An integrated humoral and cellular response is elicited in pancreatic cancer by α‐enolase, a novel pancreatic ductal adenocarcinoma‐associated antigen

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