Ibrutinib inhibits antibody dependent cellular cytotoxicity induced by rituximab or obinutuzumab in MCL cell lines, not overcome by addition of lenalidomide
(2019) In Experimental Hematology and Oncology 8(1).- Abstract
Background: The Bruton's Tyrosine Kinase (BTK)-inhibitor ibrutinib is highly active in mantle cell lymphoma (MCL) but may inhibit response to anti-CD20 antibody as previously shown in CLL models. We investigated how antibody-dependent cellular cytotoxicity (ADCC) induced by type I/II anti-CD20 antibodies was affected by treatment with ibrutinib in MCL. Furthermore, we investigated if lenalidomide, a potential sensitizer to anti-CD20 treatment, could prevent an inhibitory effect of ibrutinib. Methods: Anti-CD20 (rituximab/obinutuzumab) opsonized MCL cell lines were co-cultured with ibrutinib (± lenalidomide) - exposed effector cells, and analyzed for evaluation of cell death. Results: Cell death induced by rituximab was reduced with 75%... (More)
Background: The Bruton's Tyrosine Kinase (BTK)-inhibitor ibrutinib is highly active in mantle cell lymphoma (MCL) but may inhibit response to anti-CD20 antibody as previously shown in CLL models. We investigated how antibody-dependent cellular cytotoxicity (ADCC) induced by type I/II anti-CD20 antibodies was affected by treatment with ibrutinib in MCL. Furthermore, we investigated if lenalidomide, a potential sensitizer to anti-CD20 treatment, could prevent an inhibitory effect of ibrutinib. Methods: Anti-CD20 (rituximab/obinutuzumab) opsonized MCL cell lines were co-cultured with ibrutinib (± lenalidomide) - exposed effector cells, and analyzed for evaluation of cell death. Results: Cell death induced by rituximab was reduced with 75% at 0.5 μM ibrutinib and with 52% at 0.1 μM ibrutinib when induced by obinutuzumab, even by addition of lenalidomide. Moreover, obinutuzumab was associated with higher rate of cell death compared to rituximab. Conclusion: Ibrutinib negatively affects anti-CD20 induced cell death in MCL, not reversed by lenalidomide. Explorations of sequential administration and selective BTK-inhibitors may reveal the optimal combination of novel agents in MCL.
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- author
- Albertsson-Lindblad, Alexandra LU ; Freiburghaus, Catja LU ; Jerkeman, Mats LU and Ek, Sara LU
- organization
- publishing date
- 2019-08-06
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Antibody-dependent cell death, CD20 antibody, Ibrutinib, Lenalidomide, Mantle cell lymphoma
- in
- Experimental Hematology and Oncology
- volume
- 8
- issue
- 1
- article number
- 16
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85070479304
- pmid:31406628
- ISSN
- 2162-3619
- DOI
- 10.1186/s40164-019-0141-1
- language
- English
- LU publication?
- yes
- id
- 9af8f3c4-2fd6-4431-b38b-faf1b632013b
- date added to LUP
- 2019-08-30 14:00:13
- date last changed
- 2024-04-16 18:41:09
@article{9af8f3c4-2fd6-4431-b38b-faf1b632013b, abstract = {{<p>Background: The Bruton's Tyrosine Kinase (BTK)-inhibitor ibrutinib is highly active in mantle cell lymphoma (MCL) but may inhibit response to anti-CD20 antibody as previously shown in CLL models. We investigated how antibody-dependent cellular cytotoxicity (ADCC) induced by type I/II anti-CD20 antibodies was affected by treatment with ibrutinib in MCL. Furthermore, we investigated if lenalidomide, a potential sensitizer to anti-CD20 treatment, could prevent an inhibitory effect of ibrutinib. Methods: Anti-CD20 (rituximab/obinutuzumab) opsonized MCL cell lines were co-cultured with ibrutinib (± lenalidomide) - exposed effector cells, and analyzed for evaluation of cell death. Results: Cell death induced by rituximab was reduced with 75% at 0.5 μM ibrutinib and with 52% at 0.1 μM ibrutinib when induced by obinutuzumab, even by addition of lenalidomide. Moreover, obinutuzumab was associated with higher rate of cell death compared to rituximab. Conclusion: Ibrutinib negatively affects anti-CD20 induced cell death in MCL, not reversed by lenalidomide. Explorations of sequential administration and selective BTK-inhibitors may reveal the optimal combination of novel agents in MCL.</p>}}, author = {{Albertsson-Lindblad, Alexandra and Freiburghaus, Catja and Jerkeman, Mats and Ek, Sara}}, issn = {{2162-3619}}, keywords = {{Antibody-dependent cell death; CD20 antibody; Ibrutinib; Lenalidomide; Mantle cell lymphoma}}, language = {{eng}}, month = {{08}}, number = {{1}}, publisher = {{BioMed Central (BMC)}}, series = {{Experimental Hematology and Oncology}}, title = {{Ibrutinib inhibits antibody dependent cellular cytotoxicity induced by rituximab or obinutuzumab in MCL cell lines, not overcome by addition of lenalidomide}}, url = {{http://dx.doi.org/10.1186/s40164-019-0141-1}}, doi = {{10.1186/s40164-019-0141-1}}, volume = {{8}}, year = {{2019}}, }