milatuzumab (IMMU-115) / Gilead - LARVOL DELTA

IGHG1+ Malignant Epithelial Cell-myCAF Crosstalk via MIF-CD74/APP-CD74 Drives Early Brain Metastasis in NSCLC: Delineated via Primary Tumor-Brain Metastasis Single-cell and Spatial Transcriptomics. (PubMed, Cancer Lett) - "In vivo studies confirmed that the candidate drugs targeting CD74, doxorubicin and milatuzumab, have a tendency to inhibit EMT. IGHG1+ MEC collaborate with myCAF to shape a pro-metastatic microenvironment, with the MIF-CD74/APP-CD74 interaction network serving as a driver of NSCLC brain metastasis. CD74-targeting therapies show promising clinical potential."

Journal • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD74 • IGHG1

Regulation of PD-L1+ tumor associated macrophages by collagen expressing myCAFs and luminal progenitors in endocrine-resistant breast cancer (AACR 2026) - "Moreover, co-culture of PD-L1+ TAMs treated with FDA approved drug Milatuzumab, a CD74 inhibitor, resulted in fewer and smaller tumor spheres, underscoring the crucial function of CD74 in mediating this crosstalk. Analysis of downstream regulators confirm that CD8+ T cells are exhausted, suggesting a strongly immune-suppressive TME. Together, we identified a complex cell signaling network between myCAF-luminal progenitor expressing APP and collagens with CD74+/PD-L1+ TAMs in endocrine resistant tumors, identifying novel actionable vulnerabilities in these breast cancer patients."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • APP • CAFs • CD74 • CD8 • COL1A1 • COL4A1 • COL6A3 • IFNG • ITGB3 • PD-L1

An emerging role of CD74 in thyroid follicular cells in Hashimoto´s thyroiditis. (PubMed, Biomed Pharmacother) - "Proinflammatory cytokines IFN-γ and TNF-α were able to upregulate CD74, CD80 and HLA-DR in vitro, while the anti-CD74 antibody milatuzumab partially reduced their expression. Alternatively, MIF and CD44 expression did not change under these conditions, suggesting that IFN-γ and TNF-α may be involved in the acquisition of the APCs phenotype in TFCs. These findings implicate a possible role of CD74 in HT pathogenesis and highlight its potential as a therapeutic target through CD74 blockade in TFCs."

Journal • Endocrine Disorders • Grave’s Disease • Immunology • Inflammation • CD44 • CD74 • CD80 • IFNG • TNFA

Single-cell RNA sequencing analysis revealed the immunosuppressive remodeling of tumor-associated macrophages mediated by the MIF-CD74 axis in gastric cancer. (PubMed, Sci Rep) - "Crucially, Milatuzumab, a CD74-targeting antibody, reversed MIF-induced TAM immunosuppression in vitro. Our research provides a comprehensive map of GC-TAM heterogeneity; reveals that the MIF-CD74 axis is a key driver of TAM-mediated immune suppression; and proposes that CD74 blockade is a new therapeutic strategy for GC."

IO biomarker • Journal • Gastric Cancer • Metabolic Disorders • Oncology • Solid Tumor • APOE • CD74 • IDO1 • POLG2 • SKAP1

CD74+ Thyrocytes in Hashimoto's Thyroiditis: A Potential Therapeutic Approach (ESPE-ESE 2025) - "our data suggests a role of CD74 in HT pathogenesis. The use of milatuzumab as a CD74 inhibitor may represent a potential therapy to ameliorate immune cell reactivity."

Endocrine Disorders • Immunology • Inflammation • CD69 • CD74 • CD80 • CD86 • IFNG • IL2RA • TNFA

Mechanistic and Druggable Landscape of Liver Transplant (LT) Rejection (ATC 2024) - "In ex-vivo co-culture, a) CD74 and PSMB9 blockade with milatuzumab and bortezomib, respectively, suppressed T- and B-cell effector alloresponses (CD154, IFNg, IL-6). Immune synapses between T-cells and antigen presenting cells characterize early ACR after LT. Inhibition of antigen presentation by proteasomal inhibitors requires further study as potentially novel treatment of ACR."

Antibody-mediated Rejection • Hepatology • Pediatrics • Transplant Rejection • Transplantation • CD40LG • CD74 • CREM • HLA-DRA • IFNG • IL6 • PSMB9

A novel CAR-T cell product targeting CD74 is an effective therapeutic approach in preclinical mantle cell lymphoma models. (PubMed, Exp Hematol Oncol) - "Targeting CD74 with 74bbz CAR-T cells represents a new cell therapy to provide a potent and durable and anti-MCL activity."

CAR T-Cell Therapy • IO biomarker • Journal • Preclinical • Bone Marrow Transplantation • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD74 • MIF

The first ADC bearing the ferroptosis inducer RSL3 as a payload with conservation of the fragile electrophilic warhead. (PubMed, Eur J Med Chem) - "The robustness of the synthesis was successfully applied to another ADC associating the anti-CD74 mAb milatuzumab. The ADC induces ferroptotic cell death through reactive oxygen species accumulation and increases the activity of doxorubicin. The ADC associating trastuzumab and RSL3 may therefore offer potential applications in vectorized therapy alone or in combination with conventional chemotherapies."

Journal • Oncology • CD74 • GPX4

Phase Ib Study of SC Milatuzumab in SLE (clinicaltrials.gov) - P1; N=22; Completed; Sponsor: Gilead Sciences; Phase classification: P1/2 ➔ P1

Clinical • Phase classification • Cutaneous Lupus Erythematosus • Discoid Lupus Erythematosus • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus • Vasculitis

Experience with milatuzumab, an anti-CD74 antibody against immunomodulatory macrophage migration inhibitory factor (MIF) receptor, for systemic lupus erythematosus (SLE). (PubMed, Ann Rheum Dis) - No abstract available

Journal • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD74 • MIF

Phase Ib Study of SC Milatuzumab in SLE (clinicaltrials.gov) - P1/2; N=22; Completed; Sponsor: Immunomedics, Inc.; Recruiting ➔ Completed

Clinical • Trial completion • Complement-mediated Rare Disorders • Cutaneous Lupus Erythematosus • Discoid Lupus Erythematosus • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

[VIRTUAL] Mimicking Cytokine-driven Key Features of Arthritis Using a Human in Vitro 3D Joint Model (ACR-ARHP 2020) - "Due to the specific drug treatment (adalimumab, tocilizumab, milatuzumab), the induction of inflammation and degradation could be prevented. The results of our study showed that our human in vitro 3D OTM mimics cytokine-driven cell- and matrix-related changes - key features of RA. By combining the components in a 96-well format, we aim to provide a mid-throughput system for preclinical drug screening."

Preclinical • Immunology • Inflammation • Rheumatology • COL1A1 • CXCL8 • IL6 • LDHA • MMP1 • MMP3 • SPP1 • TNFA

Phase I Study of Milatuzumab for Graft Versus Host Disease (clinicaltrials.gov) - P1; N=12; Terminated; Sponsor: Immunomedics, Inc.; N=40 ➔ 12; Active, not recruiting ➔ Terminated; PIs agreed no safety signals were shown, drug did not appear to lessen the risk of preventing GVHD no further patients would be enrolled

Clinical • Enrollment change • Trial termination • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

[VIRTUAL] MIMICKING ARTHRITIS IN VITRO TO TEST DIFFERENT TREATMENT APPROACHES (EULAR 2020) - "All these cytokine-related effects could be antagonized with a cocktail of therapeutics (milatuzumab, adalimumab and tocilizumab). The results of our study showed cytokine related effects of both tissue components, which can be therapeutically antagonized. By combining the components in a 96 well format, we aim to provide a mid-throughput system for preclinical drug testing."

Preclinical • Immunology • Rheumatology • COL1A1 • CXCL8 • IL6 • LDHA • SPP1 • VEGFA

Q1 FY 2013 Results (Immunomedics) - Anticipated presentation of pre-clinical data at ASH (Dec 10, 2012)

Anticipated preclinical • Hematological Malignancies • Oncology

CD84 is a survival receptor for CLL cells (Oncogene) - "Both downmodulation of CD84 expression and its immune-mediated blockade induce cell death in vitro and in vivo... analysis of samples derived from an on-going clinical trial, in which human subjects were treated with humanized anti-CD74 (milatuzumab), shows a decrease in CD84 messenger RNA and protein levels in milatuzumab-treated cells... our data show that overexpression of CD84 in CLL is an important survival mechanism that appears to be an early event in the pathogenesis of the disease."

Preclinical • Non-Hodgkin’s Lymphoma

Management of Multiple Myeloma with Second-Generation Antibody-Drug Conjugates. (PubMed) - BioDrugs - "Lorvotuzumab mertansine, indatuximab ravtansine, and milatuzumab-doxorubicin are currently under clinical development for use in multiple myeloma (MM). Preliminary data from recent studies indicate that these agents induce responses in patients with relapsed and/or refractory MM and have an acceptable safety profile."

Journal • Biosimilar • Hematological Malignancies • Multiple Myeloma • Oncology

FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death (Blood) - P=NA, N=NA; Treatment of MCL cell lines and primary tumor cells with FTY720 and milatuzumab resulted in statistically significant enhanced cell death, which was synergistic in blastic variant MCL cell lines; Significant in vivo therapeutic activity of combination treatment was also demonstrated in a preclinical, in vivo model of MCL

Preclinical-other • Hematological Malignancies

Dual-targeting immunotherapy of lymphoma: Potent cytotoxicity of anti-CD20/CD74 bispecific antibodies in mantle cell and other lymphomas (Blood) - P=NA, N=NA; The juxtaposition of CD20 and CD74 on MCL cells by the HexAbs resulted in homotypic adhesion and triggered intracellular changes that include loss of mitochondrial transmembrane potential, production of ROS, rapid and sustained phosphorylation of ERKs and JNK, downregulation of pAkt and Bcl-xL, actin reorganization, and lysosomal membrane permeabilization, culminating in cell death

Preclinical-other • Hematological Malignancies

Immunomedics: Annual Report 2013 (Immunomedics) - Anticipated patent expiry in US between 2023 and 2024; Anticipated patent expiry in EU between 2023 and 2024; Anticipated patent expiry in Japan between 2023 and 2024  

Anticipated patent expiry • Oncology

Results of a phase I study of milatuzumab, a humanized anti-CD74 antibody, and veltuzumab, a humanized anti-CD20 antibody, in patients with relapsed and refractory B-cell non-Hodgkin’s lymphoma (ASH 2011) - Presentation Time: Monday, December 12, 2011, 6:00 PM-8:00 PM; P1/2, N=36; OSU-09024; Pharmacokinetic data available from 16 pts through week 10 indicated mean plasma veltuzumab and milatuzumab concentrations immediately post-infusion were 108 ± 7 and 296 ± 22 μg/mL, and mean trough levels were 47 ± 7 and 3 ± 0.3 μg/mL, respectively; 14/18 pts had evidence of antitumor activity with 22% having an objective overall response

P1 pharmacokinetic data • Hematological Malignancies

Immunomedics: Commercial Update (Immunomedics) - Anticipated patent expiry in US, Europe and Japan between 2023 and 2024

Anticipated patent expiry • Graft versus Host Disease

Emerging immune targets for the treatment of multiple myeloma. (PubMed, Immunotherapy) - "...Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab...A recent experience of CAR T-cell (B-cell maturation antigen) therapy in advanced MM has shown global response of 100%. The future of monoclonal antibodies and adoptive T cells for MM treatment seems promising."

Journal