R3Mab / Roche - LARVOL DELTA

Dual CXCR3 and CD28 Blockade Synergistically Prolongs Graft Survival and Potently Restrains Effector CD8+ T Cells (WTC 2025) - "Together, these data demonstrate that blockade of CXCR3 and CD28 pathways synergize to prolong graft survival and restrain the activation of effector CD8+ T cells. Future directions will study the mechanism by which CD8+ T cells are prevented from antigen priming under these conditions."

IO biomarker • Transplant Rejection • CD8 • CTLA4 • CXCL10 • CXCL9 • CXCR3 • SPN

Preclinical discovery and characterization of EO-1022, a site-specific glycan-conjugated anti-HER3 vc-MMAE ADC for treating solid tumors (AACR 2025) - "EO-1022 is comprised of the highly selective and clinically validated HER3 antibody, seribantumab, that is site-specifically glycan-conjugated with a cleavable valine-citrulline linker and monomethyl auristatin E (MMAE) payload to give a drug-to-antibody ratio (DAR) of 4. EO-1022 was evaluated in vitro and in vivo, with patritumab deruxtecan (patri-DXd) as a comparator. EO-1022 demonstrated target-dependent in vitro cytotoxicity and in vivo anti-tumor activity in a HER3-expressing breast cancer CDX model. Additional results on the optimization and characterization of EO-1022 will be presented, including bystander effect assays and in vivo models of HER3-positive breast cancer and EGFR mutant NSCLC. Results from preclinical studies highlight the therapeutic potential of EO-1022 for patients living with HER3-expressing cancers."

Late-breaking abstract • Preclinical • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

JSKN021, an innovative site-specific dual-payload bispecific antibody drug conjugate targeting EGFR and HER3 exhibits potent preclinical activities (AACR 2025) - "The preclinical studies suggest JSKN021, as a dual-payload EGFR/HER3 bispecific ADC, might be a promising novel antitumor therapeutic agent."

Preclinical • Oncology • EGFR • ERBB3

Histotripsy-focused ultrasound treatment abrogates tumor hypoxia responses and stimulates anti-tumor immune responses in melanoma. (PubMed, Mol Cancer Ther) - "Post-histotripsy inhibition of hypoxia and tumor growth eventually receded in parallel with cessation of CD8+ T cell influx, and pharmacological HIF-1α suppression with the MEK inhibitor Trametinib substantially augmented the therapeutic effects of histotripsy. Transient abrogation of intratumoral hypoxia and HIF-1α-associated hypoxia responses is mechanistically linked with intratumoral infiltration of activated CXCR3+/CD8+ T cells via CXCL10:CXCR3 engagement. These findings suggest that the immune effects of histotripsy may be regulated by hypoxia abrogation, and that pharmacological hypoxia abrogation could potentiate the immunotherapeutic effects of histotripsy."

Journal • Melanoma • Oncology • Solid Tumor • CD8 • CXCL10 • CXCR3 • HIF1A

Acceptability of intravenous (IV) and subcutaneous (SC) infusion administration of monoclonal antibody (mAb) combinations: VRC07-523LS with PGT121, PGDM1400, PGT121.414.LS and PGDM1400LS in phase 1 anti-HIV mAb trials (HIVR4P 2024) - "Participants consistently chose the route of administration that was used during study participation (IV or SC) or IM injection as their method of HIV prevention. Additionally, opinions of infusion visit time and recommendation of their route of administration was not different after the first and last administrations. These data support consideration for multiple routes of mAb administration appropriate for the volumes and doses needed for HIV prevention."

Late-breaking abstract • P1 data • Human Immunodeficiency Virus • Infectious Disease

Therapeutic potential of a HER3 antibody-drug conjugate for the treatment of HER3-expressing cancers (AACR 2024) - " HER3-ADC1 was evaluated in vitro and in vivo, with patritumab deruxtecan (patri-DXd) as a comparator. HER3-ADC1 demonstrated target-dependent in vitro cytotoxicity and in vivo anti-tumor activity in a HER3-expressing pancreatic cancer PDX model. Results from in vitro and in vivo studies highlight the promising therapeutic potential of a seribantumab-based ADC for patients with HER3-expressing cancers. Additional results on the optimization and characterization of HER3-ADC1 will be presented."

Breast Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Enhancing therapeutic strategies for osimertinib-resistant EGFR-mutant NSCLC: A HER3 dual-payload ADC (dpADC) with topoisomerase I and EGFR tyrosine kinase inhibitor (AACR 2024) - "U3-1402 (HER3-Dxd), an HER3 ADC, demonstrates a promising result in managing Osimertinib-resistant NSCLC. The innovative HER3 dpADC, leveraging an efficient dual enzymatic site-specific conjugation, exhibited robust anti-tumor efficacy in both in vitro and in vivo settings, surpassing single-agent treatments. Its synergistic mechanism of action presents a promising possibility for developing a more potent and the front-line therapeutic solutions in NSCLC patients who have progressed on standard therapies."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • TOP1

The study of the role of purified anti-mouse CD193 (CCR3) antibody in allergic rhinitis mouse animal models. (PubMed, Sci Rep) - "In this study, we constructed a mouse model of allergic rhinitis and intraperitoneally injected different doses of CCR3 monoclonal antibody (5, 10, and 20 uL/mg) to observe its therapeutic effect: observing changes in tissue morphology of nasal mucosa, infiltration of inflammation, and using ELISA to detect changes in relevant inflammatory mediators and cytokines, studying the role of CCR3 mAb in inhibiting CCR3-related actions on the nasal mucosa of allergic rhinitis mice. Furthermore, In addition, the therapeutic effects of intraperitoneal injection (i.p.) and intranasal administration (i.n.) were studied on the basis of effective concentrations."

Journal • Preclinical • Allergic Rhinitis • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CCR3

Targeting of HER3 potentiates the antitumor activity of paclitaxel against triple negative breast cancer (SABCS 2023) - "Our data demonstrate that increased HER3 is an effective therapeutic target for TNBC and our anti-HER3 mAb (4A7) may enhance the efficacy of paclitaxel in TNBC."

Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • ERBB3 • HER-2 • PGR

HER3 functions as an effective therapeutic target in triple negative breast cancer to potentiate the antitumor activity of gefitinib and paclitaxel. (PubMed, Cancer Cell Int) - "Our data demonstrate that increased HER3 is an effective therapeutic target for TNBC and our anti-HER3 mAb (4A7) may enhance the efficacy of gefitinib or paclitaxel in TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CXCL12 • CXCR4 • EGFR • ERBB3

Combining Anti-HER3 Antibody, HMBD-001, with EGFR Inhibition and Chemotherapy may Improve Treatment Outcomes in SqNSCLC (IASLC-WCLC 2023) - "Potency of HMBD-001 to inhibit tumor growth as monotherapy or in combination with cetuximab and/or docetaxel was evaluated using murine CDX and PDX models. An analysis of copy number variations and expression of genes in Chr3q, Chr3p and Chr7p confirms that genes involved in HER3 signaling are frequently amplified and have higher expression in squamous compared to non-squamous NSCLC. Several genetic alterations in sqNSCLC lead to HER3 and EGFR pathway activation. HMBD-001, a potent anti-HER3 mAb, in combination with EGFR inhibition and chemotherapy, has the potential to greatly improve clinical outcomes following immune-chemotherapy. Hummingbird Bioscience plans to initiate Phase Ib clinical trials in biomarker selected populations of sqNSCLC in H2, 2023."

Clinical • IO biomarker • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PIK3CA

A first-in-class bispecific antibody-drug conjugate (DM002) targeting HER3 and the juxtamembrane domain of MUC1 (AACR 2023) - "DM002 candidates showed robust anti-tumor activity in multiple CDX and PDX models of lung, breast, gastric and pancreatic cancer; most notably, DM002 candidates outperformed benchmark ADCs in BP0508 lung PDX models. Together, these data indicate that DM002 will be a promising therapeutic drug for patients with HER3 and MUC1 co-expressing tumors."

Late-breaking abstract • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ERBB3 • MUC1

Anti-HER3 antibody, HMBD-001, in combination with an EGFR inhibitor effectively inhibits tumor growth in biomarker-selected pre-clinical models of squamous cell carcinomas (AACR 2023) - P1/2 | "However, the combination of EGFR targeting antibody cetuximab with chemotherapy confers limited clinical benefit and even initially sensitive tumors often develop resistance. This study lays the foundation for testing HMBD-001 in combination with EGFR inhibitors in clinical settings. Better combination strategies of SoC and targeted therapeutics alongside a potent anti-HER3 mAb, in biomarker-selected patient populations, have the potential to meaningfully improve patient outcomes and prolong clinical benefit."

Combination therapy • Preclinical • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

BL-B01D1, a novel EGFR×HER3-targeting ADC, demonstrates robust anti-tumor efficacy in preclinical evaluation (AACR 2023) - "It is comprised of a bispecific antibody against EGFR/HER3 (SI-B001), a cathepsin B cleavable linker, and a novel topoisomerase I inhibitor agent (Ed-04), which is a derivative of the alkaloid camptothecin, driving cell cycle arrest at the S phase and subsequent apoptosis. The clinical phase I has been progressing and the available data exhibit excellent efficacy but low levels of targeted toxicity in the non-small cell lung cancer (NSCLC) treatment setting. Overall, these data suggest BL-B01D1 has potential to serve as a novel, efficacious therapeutic agent for NSCLC with similar therapeutic impact as DS-8201 has in breast cancer treatment."

Preclinical • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CTSB • EGFR • ERBB3 • HER-2

Addition of anti-VEGF overcomes the anti-PD-L1 refractoriness in a OV2944-HM-1 tumor model (AACR-NCI-EORTC 2019) - "Background: Efficacy of combination therapy with atezolizumab plus bevacizumab was shown in the IMpower150 trial. At least in the anti-PD-L1 insensitive model, this can be mainly explained by the maintained increase of intratumoral CXCL9 leading to the increased infiltration of activated effector CD8+ T cells into tumor tissue. Conflict of interest: The authors are employees of Chugai Pharmaceutical Co., Ltd."

IO Biomarker • PD(L)-1 Biomarker • Preclinical

Constitutive and induced forms of membrane-bound proteinase 3 interact with antineutrophil cytoplasmic antibodies and promote immune activation of neutrophils. (PubMed, J Biol Chem) - "This led us to the conclusion that PR3 promoted immune activation of neutrophils. We propose that blocking and/or elimination of PR3 offers a new therapeutic strategy to attenuate neutrophil activation in patients with PR3-ANCA-associated vasculitis."

Journal • Vasculitis • TNFA

"Unfortunately, development of seribantumab on hold. Seribantumab is an anti-HER3 mAb that has shown efficacy in #NRG1 fusion tumors in the CRESTONE trial. https://t.co/2Lh3CtMH9u" (@StephenVLiu)

Clinical • Oncology • NRG1

Safety and efficacy of docetaxel + b-701, a selective inhibitor of FGFR3, in subjects with advanced or metastatic urothelial carcinoma. (ASCO 2017) - P1b/2; "...Prior to atezolizumab’s approval, there were no approved treatments (txs) for pts who progressed after chemotherapy...B-701 (formerly R3Mab) is a fully human monoclonal antibody against FGFR3 that blocks activation of the wildtype and genetically activated receptor... Preliminary results show that B-701 combines safely and effectively with D in UCC, with the combination being well tolerated and showing promising ORR and PFS in pts w/ FGFR3 mut/fus. The protocol has been amended to add Cohorts 2 (B-701+D) and 3 (B-701) (n=20 pts/cohort) for pts w/ FGFR3 mut/fus+ tumors only."

Checkpoint inhibition • Clinical • Biosimilar • Bladder Cancer

Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in Locally Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC) without EGFR-Activating Mutations (IASLC-NACLC 2022) - P1 | "These data extend previous findings in patients with EGFR m NSCLC and demonstrate promising clinical activity in patients with NSCLC harboring genomic alterations other than EGFR m and in those without identified driver genomic alterations. The overall safety profile was similar to that previously reported in patients with EGFR m NSCLC."

Clinical • IO biomarker • Fatigue • Hematological Disorders • Interstitial Lung Disease • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombocytopenia • ALK • EGFR • ERBB3 • KRAS • NRAS • ROS1

Her2 interaction domain mutations in breast cancer patients are responsible for receptor switch and therapy failure against Her2 targeted medicines (EACR 2022) - "Receptor switching to other HER family members in Lapatinib resistance and HER2 receptor tyrosine kinase domain mutations have been elaborated in promoting resistance. BC cells over-expressing HER2-WT or S305C were found sensitive to Trastuzumab (P>0.001) or Neratinib (P>0.001), whereas cells with G309A, S310Y or P523S mutation were non-responder to those drugs as revealed by short-term, long-term viability, anchorage-independent growth and Immunoblot assessments. Conclusion The structural changes ensued after HER2 interaction domain mutations alters the downstream signalling cascades and impacts the therapy response to HER2 targeted medicines."

Clinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • ERBB3 • HER-2

Establishment of Novel Anti-Mouse CCR3 Monoclonal Antibodies (CMab-6 and CMab-7) by N-terminal Peptide Immunization. (PubMed, Monoclon Antib Immunodiagn Immunother) - "Kinetic analyses using flow cytometry indicated that the dissociation constants (Ks) of CMab-6 for CHO/mCCR3, P388, and J774-1 cells were 8.7 × 10 M, 1.4 × 10 M, and 1.7 × 10 M, respectively, whereas the Ks of CMab-7 for these cell lines were 3.7 × 10 M, 5.1 × 10 M, and 3.1 × 10 M, respectively. Results also indicated that CMab-6 and CMab-7 are useful for detecting cells expressing CCR3 through flow cytometry, thereby making them potentially beneficial for treating CCR3-expressing cells."

Journal • Preclinical • Allergy • Hematological Malignancies • Human Immunodeficiency Virus • Immunology • Infectious Disease • Oncology

CMab-3: A Monoclonal Antibody for Mouse CC Chemokine Receptor 3 for Flow Cytometry. (PubMed, Monoclon Antib Immunodiagn Immunother) - "Kinetic analyses using flow cytometry indicated that Ks of CMab-3 for CHO/mCCR3, P388, and J774-1 cells were 4.3 × 10 M, 2.6 × 10 M, and 2.4 × 10 M, respectively. CMab-3 could be a valuable tool for elucidating mCCR3-related biological response using flow cytometry."

Journal • Preclinical • Asthma • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Differential tumor inhibitory effects induced by HER3 extracellular subdomain-specific mouse monoclonal antibodies. (PubMed, Cancer Chemother Pharmacol) - "Some of the anti-HER3 MAbs produced in this study displayed tumor inhibitory function and may be considered promising candidates for future HER3-targeted cancer therapy."

Journal • Preclinical • Oncology • ERBB3 • HER-2

[VIRTUAL] Neurotensin increases tyrosine phosphorylation of HER3 (AACR 2021) - "The results indicate that NTS increased HER3 tyrosine phosphorylation in a ROS-/Src-/MMP-dependent manner. In summary, NTSR1 transactivates HER3 resulting in ERK and Akt phosphorylation increasing the proliferation and survival of NSCLC cells."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • HER-2 • NRG1

[VIRTUAL] Triggering the resolution of inflammation with agonistic anti-ChemR23 antibody dampens inflammation-driven carcinogenesis (AACR 2021) - "Finally, using an orthotopic triple-negative breast cancer model (4T1), while we observed a limited impact on primary tumor growth, spontaneous metastasis development in the lung was significantly inhibited by the ChemR23 agonist mAb monotherapy. Our study reveals for the first time the therapeutic potential of triggering the proresolutive pathways using an anti-ChemR23 agonistic mAb to limit chronic inflammation in the tumor microenvironment and inhibit metastasis development."

Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Mesothelioma • Oncology • Solid Tumor • Triple Negative Breast Cancer