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over2years
The development of HK013, a bispecific antibody targeting MSLN and CD137, for the treatment of MSLN+ solid tumors (AACR 2022)
R3C7 blocks the binding of MORAb-009 to MSLN, while R2G12 does not...The bispecific formats are related to the Fc receptor-mediated non-specific activation of CD137 signal, which may potentially cause safety issue. The strong antitumor activity and the lowest non-specific activation of CD137 signal of HK013 makes it the candidate worthwhile of further evaluation of its safety and efficacy.
Late-breaking abstract
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CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • MSLN (Mesothelin) • MUC16 (Mucin 16, Cell Surface Associated) • CD4 (CD4 Molecule) • TNFRSF9 (TNF Receptor Superfamily Member 9)
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amatuximab (MORAb-009)
almost3years
Immunotherapeutic Targeting of Mesothelin Positive Pediatric AML Using Bispecific T Cell Engaging Antibodies. (PubMed, Cancers (Basel))
Using antibody single-chain variable region (scFv) sequences derived from amatuximab-recognizing MSLN, and from either blinatumomab or AMG330 targeting CD3, we engineered and expressed two MSLN/CD3-targeting BsAbs: MSLN-CD3 and MSLN-CD3, respectively. These data validate the in vivo efficacy and specificity of MSLN-targeting BsAbs. Because prior MSLN-directed therapies appeared safe in humans, MSLN-targeting BsAbs could be ideal immunotherapies for MSLN-positive pediatric AML patients.
Clinical • Journal • IO biomarker
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MSLN (Mesothelin)
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MSLN expression • MSLN positive
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Blincyto (blinatumomab) • amatuximab (MORAb-009) • eluvixtamab (AMG 330)
3years
T Cell Engaging Bispecific Antibodies Produce Durable Response in Mesothelin-Positive Patient-Derived Xenograft Models of Pediatric AML (ASH 2021)
Antibody single-chain variable region (scFv) sequences derived from amatuximab recognizing MSLN and from either blinatumomab or AMG330 targeting CD3 were used to engineer and express two MSLN/CD3-targeting BsAbs: MSLN AMA -CD3 L2K and MSLN AMA -CD3 AMG respectively...Chemotherapy (DA) consisted of 3 doses of 1.5 mg/kg daunorubicin iv and 5 doses of 50 mg/kg cytarabine ip...Conclusion These data validate the efficacy of MSLN-targeting BsAbs in PDX models with endogenous MSLN expression. Because prior MSLN-directed therapies appeared safe in humans, MSLN-targeting BsAbs could be ideal immunotherapies for MSLN-positive pediatric AML patients.
Preclinical • IO biomarker
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MSLN (Mesothelin) • B2M (Beta-2-microglobulin)
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MSLN expression • MSLN overexpression • MSLN positive
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cytarabine • Blincyto (blinatumomab) • daunorubicin • CT-95 • amatuximab (MORAb-009) • eluvixtamab (AMG 330)
over3years
Mesothelin blockage by Amatuximab suppresses cell invasiveness, enhances gemcitabine sensitivity and regulates cancer cell stemness in mesothelin-positive pancreatic cancer cells. (PubMed, BMC Cancer)
Our work suggested that Amatuximab inhibits the adhesion of cancer cells to peritoneum and suppresses the stemness and viability of those, that lead to enhance the sensitivity for gemcitabine.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • MSLN (Mesothelin) • CD44 (CD44 Molecule) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1)
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MSLN expression • MSLN positive
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gemcitabine • amatuximab (MORAb-009)
over3years
Early administration of amatuximab, a chimeric high-affinity anti-mesothelin monoclonal antibody, suppresses liver metastasis of mesothelin-expressing pancreatic cancer cells and enhances gemcitabine sensitivity in a xenograft mouse model. (PubMed, Invest New Drugs)
In conclusion, our study revealed that early administration of amatuximab alone or in combination with GEM significantly suppressed the liver metastases of mesothelin-expressing pancreatic cancer cells. A phase II clinical trial of amatuximab as part of an adjuvant chemotherapy regimen for resected pancreatic cancer is expected.
Preclinical • Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • MSLN (Mesothelin)
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MSLN expression • MSLN overexpression
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gemcitabine • amatuximab (MORAb-009)
4years
[VIRTUAL] Therapeutic Targeting of Mesothelin in Acute Myeloid Leukemia with Chimeric Antigen Receptor T Cell Therapy (ASH 2020)
The VH and VL sequences from Amatuximab were used to create the scFv domain of the standard CAR (41-BB and CD3Zeta)... In this study, we demonstrate that mesothelin is a viable therapeutic target and a potential diagnostic biomarker in AML. We show that MSLN CAR T cells were highly effective in eliminating MSLN-positive AML cells in vitro and in vivo. Shedding contributes to the loss of mesothelin antigen and provides a source of soluble mesothelin that may interfere with antibody-based therapies, including CAR T cells.
CAR T-Cell Therapy
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MSLN (Mesothelin) • CD34 (CD34 molecule)
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amatuximab (MORAb-009)
5years
Mesothelin Targeting Bites for Pediatric AML: In Vivo Efficacy and Specificity (ASH 2019)
Using scFv sequences derived from Amatuximab, which recognizes the N-terminal domain of the GPI-linked ectodomain of MSLN, targeting region 1 of MSLN, and from Blinatumomab/AMG-330 targeting CD3, we engineered and expressed two kinds of BiTE molecules – a canonical BiTE and an IgG BiTE, a larger molecule with improved serum half life in vivo. 1H), suggesting that IgG BiTE was far more efficacious than canonical BiTEs (P<0.01). Taken together, these data indicate that MSLN-targeting BiTEs could be used as novel immunotherapy for pediatric AML with MSLN expression.
IO biomarker
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MSLN (Mesothelin) • B2M (Beta-2-microglobulin)
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Blincyto (blinatumomab) • amatuximab (MORAb-009) • eluvixtamab (AMG 330)