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BIOMARKER:

MSLN positive

i
Other names: MSLN, CAK1, MPF, Mesothelin
Entrez ID:
Related biomarkers:
2ms
Mesothelin CAR-T cells expressing tumor-targeted immunocytokine IL-12 yield durable efficacy and fewer side effects. (PubMed, Pharmacol Res)
IL12R54 also upregulated CXCR6 expression in the T cells through the NF-κB pathway, which facilitated T cell infiltration and persistence in the tumor tissues. In summary, the studies provide a good therapeutic option for the clinical treatment of solid tumors.
Journal • Adverse events • CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker
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IFNG (Interferon, gamma) • MSLN (Mesothelin) • CXCR6 (C-X-C Motif Chemokine Receptor 6)
|
MSLN positive
3ms
Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer (clinicaltrials.gov)
P1/2, N=36, Active, not recruiting, TCR2 Therapeutics | Recruiting --> Active, not recruiting | N=175 --> 36 | Trial completion date: Apr 2026 --> Nov 2028 | Trial primary completion date: Jul 2024 --> Nov 2028
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • IO biomarker • Metastases
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MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • cyclophosphamide • gavocabtagene autoleucel (TC-210) • fludarabine IV
3ms
A Phase 1/2 Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer (clinicaltrials.gov)
P1/2, N=6, Active, not recruiting, TCR2 Therapeutics | Trial completion date: Dec 2027 --> Oct 2028 | Trial primary completion date: Nov 2023 --> Oct 2028
Trial completion date • Trial primary completion date • Metastases
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
cyclophosphamide • fludarabine IV • TC-510
4ms
Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia. (PubMed, Int J Mol Sci)
The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating the acquisition of a rapid supply of ATP for proliferation in AML. Therefore, the targeting of mesothelin presents a potentially promising approach to mitigating the progression of AML through the inhibition of glycolysis and mitochondrial respiration in myeloid cells.
Journal
|
MSLN (Mesothelin) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
|
MSLN expression • MSLN positive
4ms
NCI10208: Testing the Combination of Anetumab Ravtansine With Either Nivolumab, Nivolumab and Ipilimumab, or Gemcitabine and Nivolumab in Advanced Pancreatic Cancer (clinicaltrials.gov)
P1, N=74, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
Trial completion date • Trial primary completion date • Combination therapy • Tumor mutational burden • Metastases
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • gemcitabine • anetumab ravtansine (BAY 94-9343) • ABP 206 (nivolumab biosimilar)
5ms
Clinical Significance Of Mesothelin Expression And Its Correlation With HER2 In Gynecologic Carcinosarcoma (ESGO 2024)
In this study, MSLN expression is widely observed in UCS. Moreover, high-MSLN expression is a favorable prognostic factor for UCS, which could be a promising therapeutic target, regardless of HER2 expression. This study was published in the Journal of Gynecologic Oncology.
Clinical
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HER-2 (Human epidermal growth factor receptor 2) • MSLN (Mesothelin)
|
HER-2 negative • HER-2 expression • MSLN expression • MSLN positive
|
VENTANA MSLN (SP74) ASSAY
6ms
Phase I Evaluation of Immunotoxin LMB-100 Administered by Normothermic, Intrapleural Perfusion Following Cytoreductive Surgery in Participants With Pleural Mesotheliomas, or Pleural Effusions From Cancers Expressing Mesothelin (clinicaltrials.gov)
P1, N=42, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2027 --> Dec 2024 | Trial primary completion date: Dec 2026 --> Dec 2024
Trial completion date • Trial primary completion date • Surgery
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
LMB-100
6ms
A Phase 1/2 Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer (clinicaltrials.gov)
P1/2, N=6, Active, not recruiting, TCR2 Therapeutics | Recruiting --> Active, not recruiting | N=140 --> 6 | Trial primary completion date: Jun 2025 --> Nov 2023
Enrollment closed • Enrollment change • Trial primary completion date • Metastases
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
cyclophosphamide • fludarabine IV • TC-510
6ms
A Study of RC88 Combined With JS001 for Advanced Solid Tumours (clinicaltrials.gov)
P1/2, N=82, Recruiting, RemeGen Co., Ltd. | Not yet recruiting --> Recruiting | Initiation date: Apr 2023 --> Jul 2023
Enrollment open • Trial initiation date
|
MSLN (Mesothelin)
|
MSLN positive
|
Loqtorzi (toripalimab-tpzi) • misitatug blivedotin (RC88)
7ms
Assessment of Novel Mesothelin-Specific Human Antibody Domain VH-Fc Fusion Proteins-Based PET Agents. (PubMed, ACS Omega)
Furthermore, PET imaging allowed us to compare the pharmacokinetics of epitope-specific VH domain-based PET tracers. Overall, these data are encouraging for the incorporation of PET imaging to assess modified VH domain structures to develop novel anti-MSLN VH domain-based therapeutics in MSLN-positive cancers as well as their companion PET imaging agents.
Journal
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MSLN (Mesothelin)
|
MSLN expression • MSLN positive
7ms
Novel mesothelin-targeted chimeric antigen receptor-modified UNKT cells are highly effective in inhibiting tumor progression. (PubMed, Pharmacol Res)
CAR-UNKT cells also demonstrated strong antitumor activity in mouse models of ovarian cancer, with the ability to migrate and infiltrate the tumor without inducing immune memory. The fast-in and -out, enhanced and prolonged tumor killing properties of CAR-UNKT suggested a novel cure option of cellular immunotherapy in the treatment of MSLN-positive solid tumors.
Journal
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IL6 (Interleukin 6) • MSLN (Mesothelin) • GZMB (Granzyme B)
|
MSLN positive
7ms
Mesothelin expression in gynecologic carcinosarcoma: clinicopathological significance and correlation with HER2 expression. (PubMed, J Gynecol Oncol)
MSLN expression is widely observed in gynecological carcinosarcomas. Moreover, high-MSLN expression is a favorable prognostic factor for UCS. MSLN could be a promising therapeutic target for UCS, even in the era of anti-HER2 therapy.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • MSLN (Mesothelin)
|
HER-2 negative • HER-2 expression • MSLN expression • MSLN positive
|
VENTANA MSLN (SP74) ASSAY
8ms
Development of a Regulated, Optimized Mesothelin Chimeric Antigen Receptor (CAR) for the Treatment of Mesothelin Positive Cancers (ASH 2023)
Contrary to the conclusions of prior studies with MSLN-targeted CARs, membrane distal epitopes were superior to membrane proximal epitopes when binders were paired with the correct spacer, and shed MSLN and MUC16 were not inhibitory for the best-performing CARs, regardless of target epitope. Furthermore, regulated expression enhanced the potency and durability of response compared to constitutive expression. This approach may improve CAR activity in patients with MSLN+ solid tumors or leukemia.
PD(L)-1 Biomarker • IO biomarker
|
IFNG (Interferon, gamma) • MSLN (Mesothelin) • MUC16 (Mucin 16, Cell Surface Associated) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • IL2 (Interleukin 2) • ICAM1 (Intercellular adhesion molecule 1) • CARS1 (Cysteinyl-TRNA Synthetase 1) • CD58 (CD58 Molecule) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
MSLN positive • PD-1 elevation
8ms
Mesothelin-targeted CAR-T therapy combined with irinotecan for the treatment of solid cancer. (PubMed, J Cancer Res Clin Oncol)
Our results suggest that irinotecan can enhance the antitumor activity of MSLN-targeted CAR T cells, and offer a promising combination therapy strategy for MSLN-positive solid tumors.
Journal
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MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
irinotecan
8ms
NCI-2018-01503: Bevacizumab and Anetumab Ravtansine or Paclitaxel in Treating Patients With Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov)
P2, N=96, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024
Trial completion date • Trial primary completion date
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MSLN (Mesothelin)
|
MSLN positive
|
Avastin (bevacizumab) • paclitaxel • Vegzelma (bevacizumab-adcd) • Avzivi (bevacizumab-tnjn) • anetumab ravtansine (BAY 94-9343)
9ms
Evaluate Mesothelin as a Biomarker for the Clinical Management of Esophageal Adenocarcinoma (EAC) (clinicaltrials.gov)
P=N/A, N=371, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024
Trial completion date • Trial primary completion date
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MSLN (Mesothelin)
|
MSLN expression • MSLN positive
9ms
Preclinical assessment of a novel human antibody VH domain targeting mesothelin as an antibody-drug conjugate. (PubMed, Mol Ther Oncolytics)
The X-ray crystal structure of full-length MSLN in complex with 3C9 reveals interaction of the 3C9 domains with two distinctive residue patches on the MSLN surface. This newly discovered VH antibody domain has a high potential as a therapeutic candidate for MSLN-expressing cancers.
Preclinical • Journal
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MSLN (Mesothelin)
|
MSLN expression • MSLN positive
9ms
Phase classification • Combination therapy • Tumor mutational burden • IO biomarker • Metastases
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CD8 (cluster of differentiation 8) • MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • gemcitabine • anetumab ravtansine (BAY 94-9343) • ABP 206 (nivolumab biosimilar)
9ms
Preclinical potency assessment of SynKIR-110, a mesothelin-specific KIR-CAR T cell therapy for mesothelioma (SITC 2023)
These data support further clinical development of SynKIR-110 in patients with advanced solid tumors. SynKIR-110 is currently being investigated in a Phase I clinical trial STAR-101 (NCT05568680).
Preclinical • CAR T-Cell Therapy
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MSLN (Mesothelin)
|
MSLN positive
|
SynKIR-110
9ms
Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors (clinicaltrials.gov)
P1, N=11, Completed, Amgen | Active, not recruiting --> Completed | Trial completion date: Sep 2023 --> Jun 2023
Trial completion • Trial completion date • Combination therapy • Metastases
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
inezetamab (AMG 994) • zeluvalimab (AMG 404)
9ms
Sequential Targeting Hybrid Nanovesicles Composed of Chimeric Antigen Receptor T-Cell-Derived Exosomes and Liposomes for Enhanced Cancer Immunochemotherapy. (PubMed, ACS Nano)
Paclitaxel (PTX)-based chemotherapy remains the main approach to treating lung cancer but systemic toxicity limits its use...Furthermore, Lip-CExo@PTX prolonged the survival time of tumor-bearing mice in a CT-26 metastatic lung cancer model. Therefore, Lip-CExo@PTX may deliver PTX to tumor cells through sequential targeted delivery and enhance the antitumor effects, providing a promising strategy for immunochemotherapy of lung cancer.
Journal • CAR T-Cell Therapy
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MSLN (Mesothelin) • GZMB (Granzyme B)
|
MSLN positive
|
paclitaxel
12ms
Phase classification • Combination therapy • Tumor mutational burden • IO biomarker • Metastases
|
CD8 (cluster of differentiation 8) • MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • gemcitabine • anetumab ravtansine (BAY 94-9343)
1year
Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors (clinicaltrials.gov)
P1, N=11, Active, not recruiting, Amgen | Trial completion date: Aug 2024 --> Sep 2023 | Trial primary completion date: Feb 2024 --> Jun 2023
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
inezetamab (AMG 994) • zeluvalimab (AMG 404)
1year
NAV-003, A Bispecific Antibody Targeting A Unique Mesothelin Epitope and CD3ε With Improved Cytotoxicity Against Humoral Immunosuppressed Tumors. (PubMed, Eur J Immunol)
Moreover, NAV-003 demonstrated good tolerability in mice and efficacy against patient-derived mesothelioma xenografts co-engrafted with human peripheral blood mononuclear cells. Together these data support the potential for NAV-003 clinical development and human proof-of-concept studies in patients with MSLN-expressing cancers.
Journal
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
1year
High mesothelin expression by immunohistochemistry predicts improved survival in pleural mesothelioma. (PubMed, Histopathology)
MSLN expression was more heterogenous in epithelioid mesothelioma than reported previously. Therefore, it would be appropriate to perform an immunohistochemical assessment of MSLN expression to stratify and assess patient suitability for mesothelin-targeted personalised therapies, such as chimeric antigen receptor T cells.
Journal
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
1year
New P1/2 trial • Metastases
|
MSLN (Mesothelin)
|
MSLN positive
|
Loqtorzi (toripalimab-tpzi) • misitatug blivedotin (RC88)
1year
Immunophenotype Analysis of Tumor-infiltrating Immune Cells to Elucidate the Mechanism of Antitumor Effect of IL-7 and CCL19 Producing CAR-T Cells against Solid Cancer (AUA 2023)
It was found that 7×19 CAR-T cells showed enhanced antitumor potential by the maintenance of their effector functions. These data support the foresight of this therapy as a treatment option for patients with mesothelin-positive renal cell carcinoma.
CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker • Immune cell
|
PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • MSLN (Mesothelin) • TNFA (Tumor Necrosis Factor-Alpha) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CCL19 (C-C Motif Chemokine Ligand 19) • GZMB (Granzyme B) • IL7 (Interleukin 7)
|
MSLN expression • MSLN positive
1year
Mesothelin-CAR-T Cells Against Cancers (clinicaltrials.gov)
P1, N=30, Recruiting, Second Affiliated Hospital of Guangzhou Medical University
New P1 trial • CAR T-Cell Therapy • IO biomarker
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
Mesothelin-CAR-T
over1year
A mesothelin targeting chimeric antigen receptor macrophage (CAR-M) for solid tumor immunotherapy: pre-clinical development of CT-1119 (AACR 2023)
We have previously developed CT-0508, a chimeric antigen receptor macrophage (CAR-M) targeting HER2 which showed efficacy in a variety of pre-clinical models and is currently in a Phase I clinical trial for patients with HER2+ solid tumors. The presented results demonstrate that CT-1119, an autologous human anti-mesothelin CAR-M, can cause phagocytosis, tumor cell killing, and pro-inflammatory cytokine release in response to stimulation with mesothelin. These results show that CAR-M is a feasible approach for the treatment of mesothelin expressing sold tumors via the potential for induction of a systemic anti-tumor response.
Preclinical • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • MSLN (Mesothelin) • TNFA (Tumor Necrosis Factor-Alpha)
|
HER-2 overexpression • MSLN expression • MSLN overexpression • MSLN positive
|
CT-0508 • CT-1119
over1year
High homogeneity of mesothelin expressionin primary and metastatic ovarian cancer (AACR 2023)
Our data demonstrate that mesothelin expression is frequent and highly homogeneous in ovarian cancer and prompt for future anti-mesothelin therapy studies in this tumor type.
Metastases
|
MSLN (Mesothelin)
|
MSLN expression • MSLN overexpression • MSLN positive
over1year
Mesothelin-targeting, nanobody-based CAR T cells effectively target solid tumors in fully immunocompetent hosts (AACR 2023)
This study constitutes a first attempt to establish an immunocompetent pre-clinical model for the study of mesothelin-targeting, nanobody-based CAR T cells in unprimed hosts. This model will facilitate the study of the dynamic changes occurring in the tumor microenvironment following nanobody-based CAR T cell therapy while also providing valuable insight into the tumor resistance mechanisms and methods to overcome them.
CAR T-Cell Therapy
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
over1year
Enrollment open • Surgery
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
LMB-100
over1year
Enrollment closed • Combination therapy • Tumor mutational burden • IO biomarker • Metastases
|
CD8 (cluster of differentiation 8) • MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • gemcitabine • anetumab ravtansine (BAY 94-9343)
over1year
High Homogeneity of Mesothelin Expression in Primary and Metastatic Ovarian Cancer. (PubMed, Appl Immunohistochem Mol Morphol)
No such switch was seen between the mesothelin-interpretable primary tumors and their nodal metastases of 59 cancers, and only 1 mesothelin-positive tumor had a mixture of positive and negative lymph node metastases. In conclusion, mesothelin expression is frequent and highly homogeneous in ovarian cancer.
Journal • Metastases
|
MSLN (Mesothelin)
|
MSLN expression • MSLN overexpression • MSLN positive
over1year
Single-arm, Open-label Clinical Study of SZ011 in the Treatment of Advanced Triple Negative Breast Cancer (clinicaltrials.gov)
P1, N=12, Not yet recruiting, First Affiliated Hospital of Shantou University Medical College
New P1 trial • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • MSLN (Mesothelin)
|
HER-2 negative • ER negative • MSLN positive • PGR negative
over1year
High mesothelin expression is correlated with non-squamous cell histology and poor survival in cervical cancer: a retrospective study. (PubMed, BMC Cancer)
MSLN was highly expressed in patients with cervical cancer, especially in those with non-SCC. High MSLN expression in the primary lesion was significantly associated with poor OS, and its expression was maintained in metastatic lesions. Our findings indicate that MSLN may be an attractive therapeutic target for cervical cancer.
Retrospective data • Journal
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
VENTANA MSLN (SP74) ASSAY
over1year
Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors (clinicaltrials.gov)
P1, N=11, Active, not recruiting, Amgen | Trial completion date: Mar 2023 --> Aug 2024 | Trial primary completion date: Jan 2023 --> Feb 2024
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
inezetamab (AMG 994) • zeluvalimab (AMG 404)
over1year
NCI-2018-01503: Bevacizumab and Anetumab Ravtansine or Paclitaxel in Treating Patients With Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov)
P2, N=96, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2022 --> Oct 2023 | Trial primary completion date: Oct 2022 --> Oct 2023
Trial completion date • Trial primary completion date
|
MSLN (Mesothelin)
|
MSLN positive
|
Avastin (bevacizumab) • paclitaxel • anetumab ravtansine (BAY 94-9343)
over1year
A Phase 1, open-label, dose finding study of NI-1801, a bispecific mesothelin x CD47 engaging antibody, in patients with mesothelin expressing solid cancers (SITC 2022)
Adverse events are assessed according to CTCAE v5, tumor response is determined according to RECIST 1.1. Key inclusion criteria include (1) histologically or cytologically confirmed diagnosis of epithelial ovarian cancer (high-grade serous or endometroid), triple-negative breast cancer, or non-squamous non-small cell lung cancer, (2) advanced, metastatic, or recurrent disease, and (3) MSLN expression with staining intensity of ≥2+ as per immunohistochemistry in ≥60% of tumor cells.
Clinical • P1 data • IO biomarker
|
MSLN (Mesothelin) • CD47 (CD47 Molecule)
|
MSLN expression • MSLN positive
|
NI-1801
over1year
Pre-clinical development of CT-1119, a mesothelin targeting chimeric antigen receptor macrophage (CAR-M), for solid tumor immunotherapy (SITC 2022)
Conclusions The presented results demonstrate that CT-1119, an autologous human anti-mesothelin CAR-M, can cause phagocytosis, tumor cell killing, and pro-inflammatory cytokine release in response to stimulation with mesothelin. These results show that CAR-M is a feasible approach for the treatment of mesothelin expressing sold tumors via the potential for induction of a systemic anti-tumor response.
Preclinical • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • MSLN (Mesothelin) • TNFA (Tumor Necrosis Factor-Alpha)
|
MSLN expression • MSLN overexpression • MSLN positive
|
CT-1119
over1year
Preliminary safety and efficacy of autologous anti-MSLN T cell engager-loaded T cells (CAB-T) in patients with mesothelin-expressing advanced solid tumors (SITC 2022)
Grade 1 cytokine release syndrome (CRS) was reported in all of the patients ≥ 3×10 6 cells/kg and only one patient dosed at 1×10 7 cells/kg developed Grade 3 CRS (quickly recovered after treatment with corticosteroid and tocilizumab)...Conclusions MSLN-CAB-T showed good preliminary safety in subjects with MSLN+ solid tumors, and MTD has not yet been reached. This provides the rationale to expand the study, especially for patients with tumors expressing higher levels of MSLN (≥60% in viable tumor cells) as a monotherapy or in combination with other agents.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
|
Actemra IV (tocilizumab)