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    DRUG CLASS:

    CD45-targeted antibody-drug conjugate

    Related drugs:
    8ms
    Alloengraftment without significant toxicity or GVHD in CD45 antibody-drug conjugate conditioned Fanconi anemia mice. (PubMed, Blood)
    Moreover, single dose anti-human CD45-ADC given to rhesus macaque nonhuman primates on days -6 or -10 was at least as myeloablative as lethal irradiation. These data suggest that CD45-ADC can potently promote donor alloengraftment and hematopoiesis without significant toxicity or severe GVHD, as seen with lethal irradiation, providing strong support for clinical trial considerations in highly vulnerable FA patients.
    Preclinical • Journal
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    FANCA (FA Complementation Group A) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • FANCG (FA Complementation Group G) • FANCC (FA Complementation Group C)
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    CD45-ADC
    almost2years
    CONDITIONING USING MGTA-45, AN ANTI-CD45 ANTIBODY-DRUG CONJUGATE, DEPLETES HSCS AND IMMUNE CELLS AND ENABLES TRANSPLANT IN NONHUMAN PRIMATES (EBMT 2023)
    A single dose of 3 mg/kg MGTA-45 resulted in long-term disease-free survival in all animals (median >330 days) while control groups (vehicle, isotype-ADC, or cytarabine standard of care) had median survival of 52-64 days (P < 0.005, n=5-8 mice/group).  Targeting CD45-expressing hematopoietic cells with MGTA-45, a novel anti-CD45-ADC, potently depleted HSCs and immune cells in vitro and in vivo and enabled donor cell engraftment in a nonhuman primate transplant model. MGTA-45 also significantly extended survival in a PDX model of AML refractory to standard of care. Overall, targeted conditioning using MGTA-45 could improve the risk-benefit profile of HSCT, expanding the patient population able to receive these potentially curative therapies.
    Immune cell
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    CD34 (CD34 molecule)
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    PTPRC expression
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    cytarabine • CD45-ADC
    over3years
    A Modified Method to Isolate Circulating Tumor Cells and Identify by a Panel of Gene Mutations in Lung Cancer. (PubMed, Technol Cancer Res Treat)
    By sequencing 72 lung cancer-associated genes, we found a high level of CNVs and gene mutations characteristic of tumor cells. We established a new CTCs staining scheme that significantly improves the detection rate and allows further analysis of CTCs characteristics at the genetic level.
    Journal • Circulating tumor cells
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    PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
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    CELLSEARCH®
    over3years
    Advanced Molecular Characterization Using Digital Spatial Profiling Technology on Immunooncology Targets in Methylated Compared with Unmethylated IDH-Wildtype Glioblastoma. (PubMed, J Oncol)
    In this small study, there was a statistical increase in CD4, CD14, CD68, CD8A, B7-H3, PDL-1, CD19, FOXP3, CD44, and STAT3 protein expression in methylated versus unmethylated GBM tumour core; however, this requires larger cohort validation. Advanced multiplex immunooncological biomarker analysis may be useful in identifying biomarkers for novel immunotherapeutic agents in GBMs.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD276 (CD276 Molecule) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • B2M (Beta-2-microglobulin) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CD44 (CD44 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • CD14 (CD14 Molecule) • CD68 (CD68 Molecule) • GZMB (Granzyme B) • FOXP3 (Forkhead Box P3) • MS4A1 (Membrane Spanning 4-Domains A1)
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    CD44 expression • STAT3 expression
    over3years
    [VIRTUAL] IDENTIFICATION AND PHENOTYPIC CHARACTERIZATION OF DISEASE-INITIATING CD34+/CD38− STEM CELLS IN BCR-ABL1-NEGATIVE MYELOPROLIFERATIVE NEOPLASMS (EHA 2021)
    Conclusion Together, we show that MPN NSC reside in a CD34+/CD38− fraction of the malignant clone and display a unique phenotype, including immune checkpoint molecules, cytokine receptors and other target antigens. Our results should support the isolation of MPN NSC and the development of NSC-eradicating therapies in MPN.
    PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • JAK2 (Janus kinase 2) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • CD47 (CD47 Molecule) • IL2RA (Interleukin 2 receptor, alpha) • CD33 (CD33 Molecule) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CALR (Calreticulin) • DPP4 (Dipeptidyl Peptidase 4)
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    JAK2 V617F • JAK2 mutation
    over3years
    [VIRTUAL] The differentiated CD47 monoclonal antibody AO-176 exhibits significant in vivo activity against xenograft models of pediatric acute lymphoblastic leukemia (ALL) (AACR 2021)
    Despite being tested in highly immune-deficient mice, the naked antibody AO-176 exhibited significant single-agent in vivo anti-leukemic activity against pediatric T-lineage ALL PDXs. The significant decrease in spleen infiltration elicited by AO-176 in 3/4 PDXs suggests on-target activity consistent with the known mechanism of action of CD47 targeting agents.
    Preclinical • Late-breaking abstract
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    CD47 (CD47 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CA 19-9 (Cancer antigen 19-9)
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    AO-176
    over3years
    [VIRTUAL] Specific anti-HER2 host immunity conferred by HER2-targeted antibody drug conjugate therapy and checkpoint blockade (AACR 2021)
    Both ADC alone (p=0.0004) and ADC+anti-PD-L1 dual treatment (p=0.01) significantly decreased CD4+FoxP3+ regulatory T cells. These results provide evidence that HER2-targeted ADC + anti-PD-L1 immunotherapy-induced B cell activation and differentiation along with the modulation of T cell subsets could confer host anti-HER2 immunity.
    Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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    CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • SDC1 (Syndecan 1) • FOXP3 (Forkhead Box P3) • CD86 (CD86 Molecule)
    4years
    [VIRTUAL] FLT3-CD3 Bispecific Antibody Specifically Eliminates Normal Hematopoietic Progenitors and AML in Humanized Mouse Models (ASH 2020)
    In addition, administration of CDX alone or in combination with PD1 in humanized mice resulted in efficient elimination of the human hematopoietic compartment from the mouse bone marrow. Based on our findings, CDX shows promise for treatment of AML with concurrent conditioning for HSCT with improved specificity compared to standard of care and even displays synergy with checkpoint inhibition of PD1.
    Preclinical • PD(L)-1 Biomarker • IO biomarker
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    FLT3 (Fms-related tyrosine kinase 3) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
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    FLT3 mutation
    4years
    [VIRTUAL] CD22 Gating for Flow Cytometric Analysis in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia after CD19 CAR-T Therapy (ASH 2020)
    In conclusion, our data on the comparison between CD22 and cCD79a expression in CD19 negative relapsed B-ALL patients revealed that, under most circumstances (with 82.5%-91.7% chance), CD22 gating alone could efficiently identify B cells in patients after CD19 CAR-T therapy, which is also a cost-effective and labor-saving strategy for routine practice compared to cCD79a gating. In case of partial or dim CD22 expression, the cCD79a gating is needed.
    IO biomarker
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    CD20 (Membrane Spanning 4-Domains A1) • CD19 (CD19 Molecule) • CD38 (CD38 Molecule) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
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    CD19 expression
    4years
    [VIRTUAL] Immune Cell Profiles in Patients Treated with Lenalidomide and Alternate Day Prednisolone Maintenance Post Upfront ASCT for Multiple Myeloma (LEOPARD Trial) (ASH 2020)
    Methods : The LEOPARD trial was a phase II, multi centre, open label, single arm study of RAP maintenance after a single melphalan conditioned (200mg/m2) ASCT as part of up-front therapy. Subsequently, durable responses to post-ASCT lenalidomide maintenance were associated with a cytotoxic, controlled immune response whereas early relapse was characterised by a more uncontrolled inflammatory response and the emergence of B-reg-like cells prior to relapse. We conclude that immune profiling at baseline and after initiation of therapy may help to predict a more sustained response to lenalidomide maintenance enabling pre-emptive tailored treatment decisions.
    Clinical • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD38 (CD38 Molecule) • CD123 (Interleukin 3 Receptor Subunit Alpha) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IL2RA (Interleukin 2 receptor, alpha) • CD33 (CD33 Molecule) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • IL7R (Interleukin 7 Receptor) • NCAM1 (Neural cell adhesion molecule 1) • CD5 (CD5 Molecule) • ICOS (Inducible T Cell Costimulator) • SDC1 (Syndecan 1) • CD14 (CD14 Molecule) • CD27 (CD27 Molecule) • GZMB (Granzyme B) • ITGAM (Integrin, alpha M) • IKZF2 (IKAROS family zinc finger 2) • NKG2D (killer cell lectin like receptor K1)
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    lenalidomide • melphalan • prednisolone
    4years
    [VIRTUAL] Novel Alkylating Agent Melflufen Displays Potent Efficacy in Plasma Cell Leukemia Samples and Other High-Risk Subtypes of Multiple Myeloma (ASH 2020)
    Results : Using the My-DST approach with 48 hour drug treatments, melflufen significantly decreased the viable MPC populations, whereas melphalan had little effect (Fig 1A)... Overall, these data support that the peptide-drug-conjugate melflufen shows a broad efficacy across samples from patients with plasma cell disorders. Patients facing poor prognoses, including those with PCL, high-risk cytogenetics and daratumumab-refractory disease, have a great need for new treatments. Thus, the encouraging ex vivo results with melflufen in samples from these aggressive subsets support further clinical exploration.
    Clinical
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD19 (CD19 Molecule) • CD38 (CD38 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • SDC1 (Syndecan 1)
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    Darzalex (daratumumab) • melphalan • Melflufen (melphalan flufenamide) • cyclophosphamide intravenous
    4years
    Therapy of Myeloid Leukemia using Novel Bispecific Fusion Proteins Targeting CD45 and 90Y-DOTA. (PubMed, Mol Cancer Ther)
    SJL leukemia mice treated with the bispecific 30F11-IgG1-C825 and 29.6 MBq (800 µCi) of 90Y-DOTA-biotin had a survival advantage compared to untreated leukemic mice (median 43 versus 30 days, respectively, p<0.0001). These data suggest bispecific Ab mediated PRIT may be highly effective for leukemia therapy and translation to human studies.
    Journal
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    PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
    4years
    [VIRTUAL] Prognostic value of baseline circulating tumor cells (CTCs) enumerations is for stage III and stage IV breast cancer (SABCS 2020)
    In this study, we showed that enumeration of baseline CTC and CTC-clusters correlated with worse prognosis even the patients were pathologically diagnosed for the same stage, which provided an additional measure to predict disease recurrence after systemic therapies especially for Stage III MBC patients.
    Circulating tumor cells
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    HER-2 (Human epidermal growth factor receptor 2) • EPCAM (Epithelial cell adhesion molecule)
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    HER-2 positive • HER-2 expression
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    Oncotype DX Breast Recurrence Score®Test
    4years
    [VIRTUAL] The detection and enumeration of circulating tumor cells (CTCs) and circulating endothelial cells (CECs) in metastatic breast cancer (SABCS 2020)
    Our data provides the first evidence of potential association between CTCs and CECs in metastatic breast cancer. The association between HER2 expression and CECs offers a potential new insight to mechanism connections between CECs and disease metastasis in MBC.
    Circulating Tumor Cells
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    EPCAM (Epithelial cell adhesion molecule) • MCAM (Melanoma Cell Adhesion Molecule) • ENG (Endoglin)
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    HER-2 positive • HER-2 expression
    over4years
    [VIRTUAL] First-in-human study of camidanlumab tesirine (ADCT-301, Cami), an anti-CD25 targeted therapy in patients (pts) with advanced solid tumours: Pharmacokinetics (PK) and biomarker evaluation (ESMO 2020)
    Funding: ADC Therapeutics SA. Clinical trial identification: NCT03621982.
    Clinical • P1 data • PK/PD data
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    CD8 (cluster of differentiation 8) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
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    camidanlumab tesirine (ADCT-301)