Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients.

7 days ago

Journal

FOLR1 ( Folate receptor alpha ) • MSLN (Mesothelin) • CEACAM5 (CEA Cell Adhesion Molecule 5) • DLL3 (Delta Like Canonical Notch Ligand 3) • CD70 (CD70 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • SDC1 (Syndecan 1) • GPNMB (Glycoprotein Nmb) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)

TROP2 expression • CD70 expression • SDC1 positive

26d

A bispecific antibody that targets the membrane-proximal region of mesothelin and retains high anticancer activity in the presence of shed mesothelin. (PubMed, Mol Cancer Ther)

Our findings indicate that by targeting the protease-sensitive region of MSLN, BsAb 5 has high MSLN-specific anticancer activity that is not inhibited by shed MSLN. BsAb 5 may be a promising immunotherapy candidate for MSLN-expressing cancers.

26 days ago

Journal

MSLN (Mesothelin)

MSLN expression

3ms

A Phase I /IIa Study of RC88-ADC in Subjects With Advanced Malignant Solid Tumors (clinicaltrials.gov)

P1/2, N=200, Recruiting, RemeGen Co., Ltd. | Trial completion date: May 2024 --> Sep 2025 | Trial primary completion date: Dec 2023 --> Sep 2024

3 months ago

Trial completion date • Trial primary completion date • Metastases

MSLN (Mesothelin)

misitatug blivedotin (RC88)

3ms

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

3 months ago

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)

3ms

An Exploratory Study on the Treatment of Advanced Solid Tumors by Fast CAR T Cells (clinicaltrials.gov)

P1, N=12, Recruiting, Shanghai Cell Therapy Group Co.,Ltd

3 months ago

New P1 trial

cyclophosphamide

5ms

A Phase I /IIa Study of RC88-ADC in Subjects With Advanced Malignant Solid Tumors (clinicaltrials.gov)

P1/2, N=200, Recruiting, RemeGen Co., Ltd. | N=51 --> 200

5 months ago

Enrollment change • Metastases

MSLN (Mesothelin)

misitatug blivedotin (RC88)

5ms

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

5 months ago

Enrollment open • Trial initiation date

MSLN (Mesothelin)

MSLN positive

Loqtorzi (toripalimab-tpzi) • misitatug blivedotin (RC88)

5ms

A Study to Assess the Safety and Tolerability of RC88 for Patients With Advanced Solid Tumours (clinicaltrials.gov)

P1, N=81, Recruiting, RemeGen Co., Ltd. | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

5 months ago

Trial completion date • Trial primary completion date • Metastases

MSLN (Mesothelin)

MSLN expression

misitatug blivedotin (RC88)

5ms

RC88 in Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer (clinicaltrials.gov)

P2, N=88, Not yet recruiting, RemeGen Co., Ltd.

5 months ago

New P2 trial

misitatug blivedotin (RC88)

6ms

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.

6 months ago

Journal

MSLN (Mesothelin)

MSLN expression • MSLN positive

7ms

Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma. (PubMed, Front Immunol)

In the exploratory cohort, low mesothelin and high COL1A1 and COL5A1 expression were associated with poor overall survival. Tumor mesothelin expression associated with the TME immune landscape predicts the risk of death for patients with MPM and could be a new target for immunotherapy in MPM.

7 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • MSLN (Mesothelin) • CD4 (CD4 Molecule) • CD68 (CD68 Molecule) • COL1A1 (Collagen Type I Alpha 1 Chain) • COL5A1 (Collagen Type V Alpha 1 Chain)

MSLN expression

7ms

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.

7 months ago

Journal

MSLN (Mesothelin)

MSLN expression • MSLN positive

irinotecan

8ms

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.

8 months ago

Preclinical • Journal

MSLN (Mesothelin)

MSLN expression • MSLN positive

8ms

NCI10208: Testing the Combination of Anetumab Ravtansine With Either Nivolumab, Nivolumab and Ipilimumab, or Gemcitabine and Nivolumab in Advanced Pancreatic Cancer (clinicaltrials.gov)

P1/2, N=74, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P1 --> P1/2

8 months ago

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) • ABP 206 (nivolumab biosimilar)

8ms

A novel MSLN×4–1BB bispecific antibody for solid tumor (SITC 2023)

Moreover, HK013-G1 is well tolerated in cynomolgus monkeys. These results show that this bsAb has the potential to develop into a new clinical therapy for cancer types with high-level MSLN expression.

8 months ago

IO biomarker

CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • MSLN (Mesothelin) • TNFRSF9 (TNF Receptor Superfamily Member 9)

MSLN expression

HK013

10ms

Pembrolizumab With or Without Anetumab Ravtansine in Treating Patients With Mesothelin-Positive Pleural Mesothelioma (clinicaltrials.gov)

P1/2, N=46, Active, not recruiting, National Cancer Institute (NCI) | N=110 --> 46 | Trial completion date: Mar 2023 --> Jul 2024 | Trial primary completion date: Mar 2023 --> Jul 2023

10 months ago

Enrollment change • Trial completion date • Trial primary completion date

PD-L1 (Programmed death ligand 1) • MSLN (Mesothelin) • CCL2 (Chemokine (C-C motif) ligand 2)

MSLN expression

Keytruda (pembrolizumab) • anetumab ravtansine (BAY 94-9343)

10ms

TACSTD2 (Trop-2) constitutes a promising antibody-drug conjugate target for patients with non-small cell lung cancer brain metastases (ESMO 2023)

Further validation is warranted in terms of protein expression. Our results underscore the potential value of gene expression profiling to identify new targets and improve patient selection in the context of NSCLC-BM ADC therapy.

10 months ago

Clinical

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • AXL (AXL Receptor Tyrosine Kinase) • MSLN (Mesothelin) • CD276 (CD276 Molecule) • CEACAM5 (CEA Cell Adhesion Molecule 5) • SLC34A2 (Solute carrier family 34 member 2) • ROR2 (Receptor Tyrosine Kinase Like Orphan Receptor 2) • PTK7 (Protein Tyrosine Kinase 7) • GPNMB (Glycoprotein Nmb) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)

HER-2 expression • TROP2 expression

10ms

Phase 1/2 Randomized Trial of Anetumab Ravtansine and Pembrolizumab Compared to Pembrolizumab for Pleural Mesothelioma - NCT03126630 (IASLC-WCLC 2023)

Accrual was closed prior to meeting accrual goals following approval of frontline ipilimumab and nivolumab. The addition of anetumab ravtansine to pembrolizumab did not result in significant dose limiting toxicities. There were no differences in confirmed response rates between patients treated with the combination of anetumab ravtansine and pembrolizumab, or pembrolizumab alone. The confirmed response rates were lower than reported previously reported for pembrolizumab in pleural mesothelioma.

10 months ago

Clinical • P1/2 data • PD(L)-1 Biomarker • IO biomarker

MSLN (Mesothelin)

MSLN expression

Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab) • anetumab ravtansine (BAY 94-9343)

10ms

An engineered T-cell engager with selectivity for high mesothelin-expressing cells and activity in the presence of soluble mesothelin. (PubMed, Oncoimmunology)

In xenograft models, NM28-2746 exhibited significant tumor suppressing activity, which was significantly enhanced by combination therapy with NM21-1480. NM28-2746, alone or in combination with NM21-1480, may overcome shortcomings of previous MSLN-targeted immuno-oncology drugs, exhibiting enhanced discrimination of high MSLN-expressing cell activity in the presence of sMSLN.

10 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

MSLN (Mesothelin)

MSLN expression

NM21-1480 • NM28-2746

10ms

Translation of the efficacy of antibody-drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88. (PubMed, Clin Transl Sci)

TSC from mice and predicted human PK were integrated to predict human efficacy dose. Results showed that 2 cell lines were sensitive to drugs, and the predicted efficacy dose was between 0.82 and 1.96 mg/kg q1w.

10 months ago

PK/PD data • Preclinical • Journal

MSLN (Mesothelin)

misitatug blivedotin (RC88)

11ms

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) | Phase classification: P1/2 --> P1

11 months ago

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

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.

1 year ago

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.

1 year ago

Journal

MSLN (Mesothelin)

MSLN expression • MSLN positive

1year

A Study of RC88 Combined With JS001 for Advanced Solid Tumours (clinicaltrials.gov)

P1/2, N=82, Not yet recruiting, RemeGen Co., Ltd.

1 year ago

New P1/2 trial • Metastases

MSLN (Mesothelin)

MSLN positive

Loqtorzi (toripalimab-tpzi) • misitatug blivedotin (RC88)

1year

Targeting Mesothelin in Solid Tumours: Anti-mesothelin Antibody and Drug Conjugates. (PubMed, Curr Oncol Rep)

After a couple of decades of clinical investigation in antibody targeting mesothelin, the therapeutic benefit is relatively modest. Novel delivery of mesothelin targeting agents, more potent payload in antibody drug conjugates and immune checkpoint inhibitor, may improve therapeutic benefit.

1 year ago

Review • Journal • IO biomarker

MSLN (Mesothelin)

MSLN expression

1year

In vitro and in vivo studies of human granzyme B fusion constructs targeting mesothelin (AACR 2023)

We developed a fusion protein (GrB-Fc-SD1) composed of human GrB and containing SD1, a novel human single-domain antibody that uniquely targets Region III of the glycoprotein, mesothelin...In addition, screening of an expanded panel of tumor cell lines for in vitro cytotoxicity is currently in progress and will be reported. In vivo efficacy studies against nude mice bearing Capan-2 xenograft models are currently underway and will also be reported.

1 year ago

Preclinical

MSLN (Mesothelin) • GZMB (Granzyme B)

MSLN expression

GrB-Fc-SD1

1year

An anti-mesothelin targeting antibody drug conjugate induces pyroptosis and ignites antitumor immunity in mouse models of cancer. (PubMed, J Immunother Cancer)

Together, these results show for the first time that tubulysin and a tubulysin containing ADC can elicit pyroptosis, and that this fiery cell death is critical for antitumor immunity and therapeutic response.

1 year ago

Preclinical • Journal

FLT3 (Fms-related tyrosine kinase 3) • MSLN (Mesothelin) • GSDME (Gasdermin E)

over1year

NCI10208: Testing the Combination of Anetumab Ravtansine With Either Nivolumab, Nivolumab and Ipilimumab, or Gemcitabine and Nivolumab in Advanced Pancreatic Cancer (clinicaltrials.gov)

P1/2, N=74, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

over 1 year ago

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

Advances in antibody-drug conjugates for gynecologic malignancies. (PubMed, Curr Opin Obstet Gynecol)

Current evidence strongly supports the use of ADCs and ongoing clinical trials will provide further information into the potential of making these drugs part of current standard practice allowing patients to be treated with a higher level of personalized cancer care.

over 1 year ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • MSLN (Mesothelin) • SLC34A2 (Solute carrier family 34 member 2)

Tivdak (tisotumab vedotin-tftv)

over1year

Mesothelin CAR-T cells secreting PD-L1 blocking scFv for pancreatic cancer treatment. (PubMed, Cancer Genet)

Following injection, there were significantly more CAR-T cells in the peripheral blood of Sec-MesoCAR-T group than that of MesoCAR-T group. This work demonstrated that the PD-L1 antibody secreted by Sec-MesoCAR-T cells relieved the immunosuppressive effect of pancreatic cancer on CAR-T cells and improved the anti-tumor activity of CAR-T cells, which has a good guiding significance for the clinical application of CAR-T cells in treating solid tumors.

over 1 year ago

Journal • CAR T-Cell Therapy

IFNG (Interferon, gamma) • IL6 (Interleukin 6) • MSLN (Mesothelin) • IL2 (Interleukin 2)

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

over 1 year ago

Trial completion date • Trial primary completion date

MSLN (Mesothelin)

MSLN positive

Avastin (bevacizumab) • paclitaxel • anetumab ravtansine (BAY 94-9343)

over1year

A Novel anti-MSLN x 4-1BB bispecific antibody with Fc effect function augments the antitumor efficacy (SITC 2022)

Compared with anti-4-1BB parent antibody and urelumab, HK013 induced weaker FcγR-mediated 4-1BB activation. Conclusions IgG1-based HK013-1 prevents tumor development by directly killing tumor cells and depleting Treg to relieve immunosuppression. Preclinical studies have shown that IgG1-based HK013-1 has good antitumor activity and safety, which may further develop its clinical potential.

over 1 year ago

Clinical

CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • MSLN (Mesothelin)

MSLN expression

HK013 • urelumab (BMS-663513)

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.

over 1 year ago

Clinical • P1 data • IO biomarker

MSLN (Mesothelin) • CD47 (CD47 Molecule)

MSLN expression • MSLN positive

NI-1801

over1year

Immunotherapy targeting mesothelin in acute myeloid leukemia. (PubMed, J Leukoc Biol)

This information suggests that MSLN may be an ideal target for the treatment of many AML-related diseases to improve the prognosis and survival rate. At present, there are a few immunotherapies targeting MSLN in AML in preclinical and clinical trials, such as antibody-drug conjugates, bispecific T-cell engagers, and chimeric antigen receptor-T cells, which opens new room for the treatment of MSLN-related AML.

over 1 year ago

Review • Journal • IO biomarker

MSLN (Mesothelin)

MSLN expression • MSLN positive

over1year

Immunotherapy for hepatobiliary cancers: Emerging targets and translational advances. (PubMed, Adv Cancer Res)

Particular focus will be on the development, biology and function of Glypican-3 (GPC3) and Mesothelin (MSLN) in the cancer progress of HCC and iCCA, respectively. By doing so, we will explore the prospects and applications of various immunotherapeutic strategies such as vaccines, monoclonal antibodies, immunotoxins, antibody-drug conjugates (ADCs) and chimeric antigen receptors (CARs) T cells that have been developed targeting GPC3 and MSLN.

over 1 year ago

Journal

MSLN (Mesothelin) • GPC3 (Glypican 3)

over1year

A Study to Assess the Safety and Tolerability of RC88 for Patients With Advanced Solid Tumours (clinicaltrials.gov)

P1, N=81, Recruiting, RemeGen Co., Ltd.

over 1 year ago

New P1 trial

MSLN (Mesothelin)

MSLN expression

misitatug blivedotin (RC88)

almost2years

Anti-mesothelin CAR-T immunotherapy in patients with ovarian cancer. (PubMed, Cancer Immunol Immunother)

The tumor partially subsided, and the patient's condition was relieved. In conclusion, this work proves the efficacy of the anti-MSLN CAR-T treatment strategy in ovarian cancer and provides preliminary data for the development of further clinical trials.

almost 2 years ago

Journal • IO biomarker

MSLN (Mesothelin)

MSLN positive

almost2years

Chimeric antigen receptor T cells engineered to recognize the P329G-mutated Fc part of effector-silenced tumor antigen-targeting human IgG1 antibodies enable modular targeting of solid tumors. (PubMed, J Immunother Cancer)

P329G-targeting CAR T cells combined with antigen-binding human IgG1 antibodies containing the P329G Fc mutation mediate pronounced in vitro and in vivo effector functions in different solid tumor models, warranting further clinical translation of this concept.

almost 2 years ago

Journal • CAR T-Cell Therapy

EGFR (Epidermal growth factor receptor) • MSLN (Mesothelin)

EGFR mutation • HER-2 expression

almost2years

Research Trend of Publications Concerning Antibody-Drug Conjugate in Solid Cancer: A Bibliometric Study. (PubMed, Front Pharmacol)

ADC agents including trastuzumab emtansine, trastuzumab deruxtecan, sacituzumab govitecan, enfortumab vedotin, and rovalpituzumab tesirine were highly studied. Further clinical trials of ADCs and designs of the next generation of ADCs are the current focuses of the field. Acquired resistance of ADCs and biomarkers for ADC therapy efficacy monitoring are future concerns.

almost 2 years ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • MSLN (Mesothelin) • NECTIN4 (Nectin Cell Adhesion Molecule 4)

Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Trodelvy (sacituzumab govitecan-hziy) • Padcev (enfortumab vedotin-ejfv) • Rova-T (rovalpituzumab tesirine)

almost2years

Activity of aPD1-MSLN-CART Cells against Metastatic Lung Cancer in a Phase 1 Trial (IASLC-WCLC 2022)

Our results provide evidence for the potential anti-tumor activity of aPD1-MSLN-CART cells in chemotherapy-refractory metastatic lung cancer.

almost 2 years ago

P1 data • CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker

CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • MSLN (Mesothelin) • TNFA (Tumor Necrosis Factor-Alpha) • CD4 (CD4 Molecule) • IL10 (Interleukin 10)

MSLN positive

2years

The Inhibitory Effects of Anti-ERC/Mesothelin Antibody 22A31 on Colorectal Adenocarcinoma Cells, within a Mouse Xenograft Model. (PubMed, Cancers (Basel))

We demonstrated that 22A31 exhibited a growth inhibitory property on HCT116. Our results implied that ERC/mesothelin-targeted therapy might be a promising treatment for colorectal cancer.

2 years ago

Preclinical • Journal

MSLN (Mesothelin)

MSLN expression