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DRUG:

Zamyl (lintuzumab)

i
Other names: SGN-33, smart M195, M195, HuG1-M195, HuG1-M195 monoclonal antibody, Hu-M195 monoclonal antibody, MOAB HuG1-M195, MOAB HuM195
Associations
Company:
Pfizer
Drug class:
CD33 inhibitor
Associations
4ms
89Zr-immunoPET-guided selection of a CD33xIL15 fusion protein optimized for antitumor immune cell activation and in vivo tumour retention in acute myeloid leukaemia. (PubMed, Eur J Nucl Med Mol Imaging)
This work demonstrates that CD33xIL15 fusion proteins are capable of targeting leukemic cells and stimulating local T cells in vitro and of concentrating in the tumour in AML xenografts. It also highlights the importance of 89Zr-immunoPET to guide the development and selection of tumour-targeted antibody-cytokine fusion proteins.
Preclinical • Journal • Immune cell
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CD33 (CD33 Molecule) • IL15 (Interleukin 15)
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Zamyl (lintuzumab)
6ms
Developing a membrane-proximal CD33-targeting CAR T cell. (PubMed, J Immunother Cancer)
Showing for the first time that a membrane-proximal CAR is superior to a membrane-distal one in the setting of CD33 targeting, our results demonstrate the rationale for targeting membrane-proximal epitopes with high-affinity binders. We also demonstrate the importance of optimizing CAR T cells for functionality in settings of both low antigen density and clinically relevant patient-derived models.
Journal • CAR T-Cell Therapy
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CD33 (CD33 Molecule)
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Zamyl (lintuzumab)
8ms
Targeting CD33+ acute myeloid leukemia with GLK-33, a lintuzumab-auristatin conjugate with a wide therapeutic window. (PubMed, Mol Cancer Ther)
While previous CD33-targeting antibody-drug conjugates (ADCs) like gemtuzumab ozogamicin (GO, Mylotarg) have shown efficacy in AML treatment, they have suffered from toxicity and narrow therapeutic window...The development of GLK-33 addresses the limitations of previous ADCs, offering a wider therapeutic window, improved tolerability, and activity against drug-resistant leukemia cells. These findings encourage further exploration of GLK-33 in AML through clinical trials.
Journal
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CD33 (CD33 Molecule)
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CD33 positive
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Mylotarg (gemtuzumab ozogamicin) • Zamyl (lintuzumab)
1year
Phase 1/2 Study of Donor-Derived Anti-CD33 Chimeric Antigen Receptor Expressing T Cells (VCAR33) in Patients with Relapsed or Refractory Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation (ASH 2023)
CD33 is a preferential target for AML CAR T cell therapy as it is expressed on the majority (>80%) of AML blasts and because prior clinical experience with gemtuzumab ozogamicin (GO; tradename: MylotargTM) has demonstrated the safety and efficacy of targeting CD33...Patients will receive lymphodepletion on days -5 to -2 with fludarabine (total 120 mg/m2) and cyclophosphamide (total 1000 mg/m2) followed by infusion of VCAR33 on Day 0...*NCT number pending. Clinical trial information submitted to CT.gov on July 19, 2023.
Clinical • P1/2 data
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CD33 (CD33 Molecule)
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cyclophosphamide • Mylotarg (gemtuzumab ozogamicin) • fludarabine IV • VCAR33ALLO • Zamyl (lintuzumab)
1year
Preclinical Characterization of the Anti-Leukemia Activity of the CD33/CD16/NKG2D Immune Modulating TriNKET® BMS-986357 (CC-96191) (ASH 2023)
CD33 is widely expressed by myeloid cells and is a validated drug target in acute myeloid leukemia (AML), as shown by the benefit of some patients from the CD33 antibody-drug conjugate gemtuzumab ozogamicin (GO)...In summary, our findings demonstrate that BMS-986357 TriNKET® has potent CD33-dependent cytolytic activity in vitro against human AML cells, supporting the drug's exploration in early phase clinical trials. One such trial (NCT04789655) has opened accrual for adults with relapsed/refractory AML.
Preclinical
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IFNG (Interferon, gamma) • IL6 (Interleukin 6) • CD33 (CD33 Molecule) • CSF2 (Colony stimulating factor 2) • FCGR3A (Fc Fragment Of IgG Receptor IIIa) • NKG2D (killer cell lectin like receptor K1)
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CD33 expression
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Mylotarg (gemtuzumab ozogamicin) • Zamyl (lintuzumab)
1year
An MHC class II targeted immunotherapy for CD33-positive pediatric acute myeloid leukemia (SITC 2023)
CD33-M2T has demonstrated clear advantages over anti-CD33 monoclonal antibodies (e. g. , gemtuzumab, lintuzumab), including the ability to bind to the truncated alternatively spliced version of CD33, long duration of action, and no overt toxicities in mice. Conclusions These experiments demonstrate the preclinical potential of an innovative immunotherapy targeting CD33-positive childhood AML.
Clinical • IO biomarker
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CD33 (CD33 Molecule)
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CD33 positive • CD33 expression
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Mylotarg (gemtuzumab ozogamicin) • Zamyl (lintuzumab)
over1year
Targeting myeloid-derived suppressor cells with actinium-225 lintuzumab, a CD33 antibody radioconjugate to enhance antitumor immunity (AACR 2023)
In this study, we demonstrate CD33 ARC alpha targeted radiotherapy depletes human CD33 positive immune suppressing MDSCs present in multiple cancer types, to enhance antitumor immunity. These findings present a translatable strategy that supports further evaluation of 225Ac lintuzumab as a MDSC targeting agent to improve the efficacy of antitumor therapies.
CD33 (CD33 Molecule) • CD34 (CD34 molecule)
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CD33 positive
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Actimab-A (lintuzumab-Ac225) • Zamyl (lintuzumab)
over2years
Where do we stand with radioimmunotherapy for acute myeloid leukemia? (PubMed, Expert Opin Biol Ther)
An I-labeled CD45 antibody (Iomab-B [apamistamab-I131]) is currently studied in the registration-type phase 3 SIERRA trial (NCT02665065) for this purpose...Clinical efforts with At-labeled CD45 antibodies and Ac-labeled CD33 antibodies (e.g. Ac-lintuzumab [Actimab-A]) are ongoing. A first anti-AML RIT may soon become available. This might propel further work to develop RIT-based treatments for AML, with many such efforts already ongoing.
Journal
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CD33 (CD33 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
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Actimab-A (lintuzumab-Ac225) • Iomab-B (I-131-apamistamab) • Zamyl (lintuzumab)
3years
Systematic preclinical evaluation of CD33-directed chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia defines optimized construct design. (PubMed, J Immunother Cancer)
CD33 is a critical antigen for potential immunotherapeutic targeting in patients with AML. Based on this rigorous preclinical evaluation, our validated clinical grade lintuzumab-CD28/CD3ζ CD33CART immunotherapy is now under evaluation in a first-in-child/first-in-human phase 1 clinical trial for children and adolescents/young adults with relapsed/refractory AML.
Preclinical • Journal • CAR T-Cell Therapy
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CD19 (CD19 Molecule) • CD33 (CD33 Molecule) • TNFRSF9 (TNF Receptor Superfamily Member 9)
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Mylotarg (gemtuzumab ozogamicin) • Zamyl (lintuzumab)
almost4years
225Ac-labeled CD33-targeting antibody reverses resistance to Bcl-2 inhibitor venetoclax in acute myeloid leukemia models. (PubMed, Cancer Med)
There results suggest that the combination of Ac-lintuzumab with venetoclax is a promising therapeutic strategy for the treatment of patients with venetoclax-resistant AML. Clinical trial of this combination therapy (NCT03867682) is currently ongoing.
Journal
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MCL1 (Myeloid cell leukemia 1) • CD33 (CD33 Molecule)
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MCL1 expression
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Venclexta (venetoclax) • cytarabine • Actimab-A (lintuzumab-Ac225) • Zamyl (lintuzumab)