Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy

Roit, Fabio Da; Engelberts, Patrick J.; Taylor, Ronald P.; Breij, Esther C.W.; Gritti, Giuseppe; Rambaldi, Alessandro; Introna, Martino; Parren, Paul W.H.I.; Beurskens, Frank J.; Golay, Joseé

doi:10.3324/haematol.2014.107011

Cited by 139 publications

(161 citation statements)

References 51 publications

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“…These data confirm previous reports that ibrutinib inhibits antibodydependent phagocytosis with an IC 50 of 1-3 mM. 4,6 Although monocytes/macrophages express BTK, the lower IC 50 for ibrutinib and the fact that acalabrutinib had little effect on phagocytosis indicate that kinases situated downstream of Fcg receptors other than BTK, such as Hck, FgR or Lyn, and reported to be differentially inhibited by acalabrutinib and BTK, 1 may be involved in this phenomenon. This hypothesis does, however, remain to be investigated in detail.…”

Section: A B Csupporting

confidence: 79%

“…3,4 The different behaviors of ibrutinib and acalabrutinib in ADCC are probably due to the different off-target effects of these drugs on kinases such as ITK or TEC, known to be differentially inhibited by ibrutinib and acalabrutinib, 1 and implicated in T-and NK-cell activation. 7 This hypothesis needs to be investigated further.…”

Section: A B Cmentioning

confidence: 99%

“…4,5 We therefore analyzed the effect of acalabrutinib on NKcell degranulation in comparison with that of ibrutinib in our standard assays. We first used purified peripheral blood mononuclear cells from healthy donors as effectors, anti-CD20 obinutuzumab and the MEC1 CLL B-cell line as the target.…”

Section: A B D Cmentioning

confidence: 99%

“…(A) Human macrophages, differentiated in vitro by macrophage colony-stimulating factor, were pretreated with increasing concentrations of ibrutinib (IBT) or acalabrutinib (ACP) for 1 h at 37°C, and then incubated with CFSE-labeled CLL B cells opsonized with 1 mg/mL cetuximab (CET) or rituximab (RTX) antibodies. 4 After a further 2 h at 37°C, cells were stained with CD11b-PE and CD19-APC and phagocytosis was measured by flow cytometry. Percentage phagocytosis, defined as CD11b + CFSE + CD19 -cells with respect to total CD11b + cells, is shown.…”

Section: A B D Cmentioning

confidence: 99%

“…[1][2][3] BTK inhibitors are often combined with anti-CD20 antibodies in the clinic, but ibrutinib interferes with some of the cell-mediated mechanisms of action of anti-CD20 antibodies, such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis, perhaps due to inhibition of other BTK family kinases such as ITK or TEC. [4][5][6] The aim of this work was to verify whether acalabrutinib differs from ibrutinib with respect to inhibition of ADCC and antibody-dependent phagocytosis, induced by anti-CD20 rituximab and obinutuzumab. Unlike ibrutinib, acalabrutinib did not interfere with any of the anti-tumor, immune-mediated mechanisms of anti-CD20 antibodies.…”

mentioning

confidence: 99%

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The specific Bruton tyrosine kinase inhibitor acalabrutinib (ACP-196) shows favorable in vitro activity against chronic lymphocytic leukemia B cells with CD20 antibodies

2017

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Section: A B Csupporting

confidence: 79%

Section: A B Cmentioning

confidence: 99%

Section: A B D Cmentioning

confidence: 99%

Section: A B D Cmentioning

confidence: 99%

mentioning

confidence: 99%

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The specific Bruton tyrosine kinase inhibitor acalabrutinib (ACP-196) shows favorable in vitro activity against chronic lymphocytic leukemia B cells with CD20 antibodies

2017

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Multifunctional Nanovaccine Sensitizes Breast Cancer to Immune Checkpoint Therapy

Peres,

Matos,

Carreira

et al. 2024

Adv Funct Materials

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Breast cancer is the primary cause of cancer‐related death in women worldwide. Breast cancer subtypes are characterized by different gene expression patterns, which drive their prognostic factors and therapeutic options. Among them, triple‐negative breast cancer (TNBC) is one of the deadliest due to its aggressiveness, high rate of early recurrence and distant metastases, and limited therapeutic options. Despite the recent approval of monoclonal antibodies targeting programmed cell death protein 1 (PD‐1) or its ligand (PD‐L1) for the treatment of TNBC patients with a locally recurrent unresectable or metastatic tumor expressing PD‐L1, their response rate is very modest. It is reported that polymeric nanoparticle (NP)‐based cancer vaccines, co‐entrapping tumor‐associated antigens, Toll‐like receptor ligands and small interfering RNA (siRNA) targeting the expression of the immunosuppressive cytokine transforming growth factor (TGF)‐β1 by dendritic cells, sensitized TNBC to the agonist immune checkpoint OX40, inhibiting tumor growth and increasing overall survival. This anti‐tumor immune‐mediated effect is also observed in a luminal type of mammary cancer similar to human disease. Therefore, these synergistic anticancer effects of αOX40 and the antigen‐specific adaptive immunity induced by nanovaccine‐mediated TGF‐β silencing may guide the development of novel combination regimens able to improve the response rate to this aggressive tumor.

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Strategies for overcoming resistance to Bruton's tyrosine kinase inhibitor zanubrutinib

Dostálová,

Kryštof

2024

Hematological Oncology

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Bruton's tyrosine kinase (BTK) inhibitors have revolutionized the treatment of B‐cell malignancies. They target BTK, a key effector in the B‐cell receptor (BCR) signaling pathway, crucial for B‐cell survival and proliferation. The first‐in‐class irreversible BTK inhibitor, ibrutinib, was approved for various B‐cell malignancies but has limitations due to off‐target effects. Second‐generation inhibitors, such as acalabrutinib and zanubrutinib, offer improved selectivity and reduced side effects. However, resistance to BTK inhibitors, driven by BTK mutations, remains a challenge. Combinatorial therapies with PI3K inhibitors, immune checkpoint inhibitors, BH3 mimetics, and anti‐CD20 antibodies show promise in overcoming resistance. Noncovalent BTK inhibitors and proteolysis‐targeting chimeras (PROTACs) are emerging strategies with potential to combat resistance. Overall, advancements in BTK‐targeted therapies provide hope for improved outcomes in patients with B‐cell malignancies and a promising avenue to address drug resistance. Further research is needed to optimize combination therapies and identify optimal treatment regimens.

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Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy

Cited by 139 publications

References 51 publications

The specific Bruton tyrosine kinase inhibitor acalabrutinib (ACP-196) shows favorable in vitro activity against chronic lymphocytic leukemia B cells with CD20 antibodies

The specific Bruton tyrosine kinase inhibitor acalabrutinib (ACP-196) shows favorable in vitro activity against chronic lymphocytic leukemia B cells with CD20 antibodies

Multifunctional Nanovaccine Sensitizes Breast Cancer to Immune Checkpoint Therapy

Strategies for overcoming resistance to Bruton's tyrosine kinase inhibitor zanubrutinib

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