matuzumab (EMD 72000) / Takeda, EMD Serono - LARVOL DELTA

Simultaneous targeting of EGFR-positive TNBC xenografts using epitope-specific [225Ac]Ac-labeled nimotuzumab and [161]Tb-labeled matuzumab results in enhanced therapeutic effects (SNMMI 2025) - "The combination therapy of [225Ac]Ac-Macropa-nimotuzumab and [161Tb]Tb-NETA-matuzumab demonstrates an accelerated therapeutic response against EGFR-overexpressing tumors compared to monotherapy with parent radioimmunoconjugates. This warrants further investigation."

IO biomarker • Oncology • Triple Negative Breast Cancer • EGFR

Simultaneous targeting of EGFR-positive TNBC xenografts using epitope-specific [225Ac]Ac-labeled nimotuzumab and [161]Tb-labeled matuzumab results in enhanced therapeutic effects (SNMMI 2025) - "The combination therapy of [225Ac]Ac-Macropa-nimotuzumab and [161Tb]Tb-NETA-matuzumab demonstrates an accelerated therapeutic response against EGFR-overexpressing tumors compared to monotherapy with parent radioimmunoconjugates. This warrants further investigation."

IO biomarker • Oncology • Triple Negative Breast Cancer • EGFR

Simultaneous targeting of EGFR-positive TNBC xenografts using epitope-specific [225Ac]Ac-labeled nimotuzumab and [161]Tb-labeled matuzumab results in enhanced therapeutic effects (SNMMI 2025) - "The combination therapy of [225Ac]Ac-Macropa-nimotuzumab and [161Tb]Tb-NETA-matuzumab demonstrates an accelerated therapeutic response against EGFR-overexpressing tumors compared to monotherapy with parent radioimmunoconjugates. This warrants further investigation."

IO biomarker • Oncology • Triple Negative Breast Cancer • EGFR

An Anti-EGFR Antibody-Drug Radioconjugate Labeled with Actinium-225 Elicits Durable Anti-Tumor Responses in KRAS and BRAF Mutant Colorectal Cancer. (PubMed, Cancer Res) - "PET imaging using the non-overlapping anti-EGFR radioimmunoconjugate [89Zr]Zr-DFO-matuzumab before and after treatment of orthotopic CRC xenografts showed that 1/5 mice from the treatment group had complete remission while metastatic spread was prevented in the other mice (4/5). These results show that treatment with [225Ac]Ac-macropa-nimotuzumab-PEG6-DM1 is a potential therapeutic approach for KRAS mutant and BRAFV600E mutant metastatic CRC."

Journal • Colorectal Cancer • Fibrosarcoma • Oncology • Sarcoma • Solid Tumor • BRAF • KRAS

Evaluation of a cIEF Fractionation Workflow for Offline MS Analysis of Charge Variants of the Monoclonal Antibody Matuzumab. (PubMed, Electrophoresis) - "Preliminary results with other antibodies indicated that the concentration range for MS experiments needs further investigation. Future work will aim to optimize sensitivity, selectivity, analysis time, and reproducibility."

Journal

225Ac-labeled anti-EGFR antibody drug radioconjugate elicits durable anti-tumor responses in mouse models of colorectal cancer (EANM 2024) - "Eighteen-membered macrocyclic bifunctional chelator p-Bz-SCN-macropa or deferoxamine (DFO) were used to conjugate nimotuzumab-PEG6-DM1 or matuzumab for radiolabeling with 225Ac and 89Zr, respectively. [225Ac]Ac-Macropa-nimotuzumab-PEG6-DM1 is very effective against EGFR-positive CRC models and warrants further investigation."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • DLD • KRAS

Enhancing neutrophil cytotoxicity of a panel of clinical EGFR antibodies by Fc engineering to IgA3.0. (PubMed, Mol Cancer Ther) - "Therefore, we reformatted six therapeutic EGFR antibodies (cetuximab, panitumumab, nimotuzumab, necitumumab, zalutumumab, and matuzumab) into the IgA3.0 format, which is an IgA2 isotype that has been adapted for clinical application. IgA3.0 matuzumab exhibited reduced receptor internalization compared to the other antibodies, possibly accounting for its superior in vivo Fc-mediated tumor cell killing efficacy. In conclusion, reformatting EGFR antibodies into an IgA3.0 format increased Fc-mediated killing while retaining Fab-mediated functions and could therefore be a good alternative for the currently available antibody therapies."

Journal • Oncology • EGFR

89Zr-matuzumab and 225Ac-matuzumab as a theranostic for epidermal growth factor receptor-positive KRAS wild-type colorectal and breast cancer xenografts (AACR 2024) - "225Ac-matuzumab shows very promising outcomes in KRAS-mutant mCRC models and breast cancer models and warrants further investigation."

Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRAF • EGFR • KRAS

Pharmacophore-based virtual screening approaches to identify novel molecular candidates against EGFR through comprehensive computational approaches and in-vitro studies. (PubMed, Front Pharmacol) - "The use of TK inhibitors (gefitinib, erlotinib, lapatinib, and afatinib) and monoclonal antibodies (cetuximab, panitumumab, and matuzumab) in the treatment of advanced-stage cancer is very common. MTT assay, gene expression analysis (BAX, BCL-2, and β-catenin), apoptosis analysis, TEM, cell cycle assay, ELISA, and cell migration assays were conducted to perform the cell death analysis of lung cancer and breast cancer, compared to the marketed product. The MTT assay exhibited 80% cell death for 75 µM and 100µM; however, flow cytometry analysis with the IC value demonstrated that the selected compound induced higher apoptosis in MCF-7 (30.8%) than in A549."

IO biomarker • Journal • Preclinical • Breast Cancer • Colon Cancer • Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • BAX • BCL2 • CTNNB1 • EGFR

Simultaneous Imaging and Therapy Using Epitope-Specific Anti-Epidermal Growth Factor Receptor (EGFR) Antibody Conjugates. (PubMed, Pharmaceutics) - "Treatment resulted in complete remission of the SNU-C2B tumor in 2/3 mice. Matuzumab and nimotuzumab are noncompeting and can be used simultaneously."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Milking the Cow: Cattle-Derived Chimeric Ultralong CDR-H3 Antibodies and Their Engineered CDR-H3-Only Knobbody Counterparts Targeting Epidermal Growth Factor Receptor Elicit Potent NK Cell-Mediated Cytotoxicity. (PubMed, Front Immunol) - "Binning experiments revealed epitope targeting of domains I, II, and IV of EGFR with none of the generated binders competing with Cetuximab, Matuzumab, or EGF for binding to EGFR. Besides slightly to moderately diminished capacities, these engineered Knobbodies largely retained main properties of their parental antibodies such as cellular binding and triggering of ADCC. Hence, Knobbodies might emerge as promising tools for biotechnological applications upon further optimization."

Journal • Oncology • EGFR

Most clinically approved anti-EGFR antibodies fail to neutralize EGFRvIII, explaining their lack of efficacy in high-grade glioma (AACR 2018) - "We have tested the efficacy and mechanism of action of the majority of known FDA-approved or preclinical anti-EGFR antibodies [panitumumab, cetuximab, necitumumab, nimotuzumab, matuzumab and chimeric 806 (ch806)] against five primary EGFRvIII-bearing glioma lines. Collectively, our results challenge the existing premise that EGFRvIII is neutralized and degraded by EGFR antibodies and demonstrate that both wtEGFR and EGFRvIII must be neutralized for maximum antitumor effect. These results may help explain why existing antibodies such as cetuximab and nimotuzumab have failed in clinical trials in glioma and provide rationale that panitumumab may offer a superior and effective candidate for a further clinical trial in glioma."

Clinical • Solid Tumor

The effects of somatic mutations on EGFR interaction with anti-EGFR monoclonal antibodies: Implication for acquired resistance. (PubMed, Proteins) - "The aim of the current study was to perform computational analysis to investigate the structural implications of the EGFR somatic mutations on its complexes with the four anti-EGFR mAbs (Cetuximab, Panitumumab, Necitumumab, and Matuzumab). We found that EGFR and EGFR in complex with Cetuximab, EGFR , and EGFR in complex with Panitumumab and EGFR in complex with Necitumumab have a weakest binding affinity in comparison to EGFR in complex with the relevant monoclonal antibody. Taken together with the results obtained from docking analysis and MD simulations, the present findings may suggest that, the S492R and V441I mutations confer resistance to Cetuximab, R377S and S447Y mutations mediate resistance to Panitumumab and finally, V441I mutation also confers resistance to Necitumumab."

Journal • Oncology

Identification of a novel anti-EGFR nanobody by phage display and its distinct paratope and epitope via homology modeling and molecular docking. (PubMed, Mol Immunol) - "Docking analysis revealed that the paratope focused on CDR2 loop of the identified nanobody. The identified nanobody potently cover part of the epitope of Matuzumab and Nb 9G8, which indicated that it blocked EGFR by preventing dimerization of the receptors."

Journal • Oncology • EGFR

Ultrabright terbium nanoparticles for FRET biosensing and in-situ imaging of epidermal growth factor receptors. (PubMed, Chemistry) - "Second, in-situ detection of ligand-receptor binding on cells was accomplished with TbNP-antibody (Matuzumab) conjugates that could specifically bind to transmembrane epidermal growth factor receptors (EGFR). High specificity and sensitivity were demonstrated by time-gated imaging of EGFR on both strongly (A431) and weakly (HeLa and Cos7) EGFR-expressing cell lines, whereas non-expressing cell lines (NIH3T3) and EGFR-passivated A431 cells did not show any signals. Despite the relatively large size of TbNP-antibody conjugates, they could be internalized by A431 cells upon binding to extracellular EGFR, which showed their potential as bright and stable luminescence markers for intracellular signalling."

Journal • EGFR

Semi-synthetic vNAR libraries screened against therapeutic antibodies primarily deliver anti-idiotypic binders. (PubMed, Sci Rep) - "Moreover, a two-step procedure involving vNAR-functionalized beads was employed for the enrichment of potentially bispecific cetuximab × matuzumab antibody constructs. In conclusion, semi-synthetic and CDR3-randomized vNAR libraries in combination with yeast display enable the fast and facile identification of anti-idiotypic vNAR domains targeting monoclonal antibodies primarily in an anti-idiotypic manner."

Journal • Biosimilar • Oncology

Improving antibody-based-therapies by chemical engineering of antibodies with multimeric cell-penetrating peptides for elevated intracellular delivery. (PubMed, J Control Release) - "Applicability was proven for matuzumab, trastuzumab and the ADC Kadcyla®. Cytotoxicity studies of tCPP-conjugates of Kadcyla® resulted in a sixfold increased cytotoxicity proving the potential of chemical modification strategies to extend the applicability of biologicals. This constitutes a significant step towards next-generation antibody-based therapeutics."

Journal

Most clinical anti-EGFR antibodies do not neutralize both wtEGFR and EGFRvIII activation in glioma. (PubMed, Neuro Oncol) - "We discovered a previously unknown major resistance mechanism in glioma in that most EGFR domain III-targeting antibodies do not neutralize EGFRvIII. The superior in vitro and in vivo anti-tumor activity of panitumumab support further clinical testing of this antibody against EGFRvIII-stratified glioma."

Clinical • Journal