American Association for Cancer Research
Browse
mct-23-0518_supplementary_figure_7_suppsf7.pdf (119.78 kB)

Supplementary Figure 7 from Inhibition of MALT1 and BCL2 Induces Synergistic Antitumor Activity in Models of B-Cell Lymphoma

Download (119.78 kB)
journal contribution
posted on 2024-07-02, 07:41 authored by Joshua P. Plotnik, Adam E. Richardson, Haopeng Yang, Estela Rojas, Velitchka Bontcheva, Colleen Dowell, Sydney Parsons, Ashley Wilson, Vida Ravanmehr, Christine Will, Paul Jung, Haizhong Zhu, Sarathy Karunan Partha, Sanjay C. Panchal, Raghuveer Singh Mali, Frederick J. Kohlhapp, Ryan A. McClure, Cyril Y. Ramathal, Mariam D. George, Manisha Jhala, Nathaniel L. Elsen, Wei Qiu, Russell A. Judge, Chin Pan, Anthony Mastracchio, Jared Henderson, Jonathan A. Meulbroek, Michael R. Green, William N. Pappano

MALT1 and BCL2 inhibition do not antagonize each other in monotherapy sensitive patient derived xenografts

Funding

AbbVie (Allergan)

History

ARTICLE ABSTRACT

The activated B cell (ABC) subset of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic B-cell receptor signaling and associated with poor outcomes when treated with standard therapy. In ABC-DLBCL, MALT1 is a core enzyme that is constitutively activated by stimulation of the B-cell receptor or gain-of-function mutations in upstream components of the signaling pathway, making it an attractive therapeutic target. We discovered a novel small-molecule inhibitor, ABBV-MALT1, that potently shuts down B-cell signaling selectively in ABC-DLBCL preclinical models leading to potent cell growth and xenograft inhibition. We also identified a rational combination partner for ABBV-MALT1 in the BCL2 inhibitor, venetoclax, which when combined significantly synergizes to elicit deep and durable responses in preclinical models. This work highlights the potential of ABBV-MALT1 monotherapy and combination with venetoclax as effective treatment options for patients with ABC-DLBCL.

Usage metrics

    Molecular Cancer Therapeutics

    Categories

    Keywords

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC