A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy
Anti-CD20 treatment represents a therapeutic benefit for patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing patients. Among them, the combination of anti-CD20 and IL-2 that induces T cell response has been hampered by the expansion of FoxP3+ Treg...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | OncoImmunology |
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| Online Access: | http://dx.doi.org/10.1080/2162402X.2020.1770565 |
| _version_ | 1818740069058478080 |
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| author | Ana Victoria Casadesús Claire Deligne Béré Kadjdiatou Diallo Katya Sosa Nathalie Josseaume Circe Mesa Kalet León Tays Hernández Jean-Luc Teillaud |
| author_facet | Ana Victoria Casadesús Claire Deligne Béré Kadjdiatou Diallo Katya Sosa Nathalie Josseaume Circe Mesa Kalet León Tays Hernández Jean-Luc Teillaud |
| author_sort | Ana Victoria Casadesús |
| collection | DOAJ |
| description | Anti-CD20 treatment represents a therapeutic benefit for patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing patients. Among them, the combination of anti-CD20 and IL-2 that induces T cell response has been hampered by the expansion of FoxP3+ Tregs that strongly express the high affinity IL-2 receptor (IL-2R αβγ). We explore here the anti-tumor effect of an anti-CD20 antibody combined with a mutated IL-2 (no-alpha mutein) which has a disrupted affinity for the IL-2R αβγ. We demonstrate that anti-CD20/no-alpha mutein combination significantly augments the survival rate of mice challenged with huCD20+ cells as compared to animals treated with anti-CD20 ± IL-2. Moreover, the combination with no-alpha mutein but not IL-2 provokes an increase of granzyme B and perforin in splenic NK and CD8+ T cells, a reduction of Tregs and an increase in activated macrophages. The former combination also induces a T helper profile different from that obtained with IL-2, with an earlier polarization to Th1 and no increase in Th17. The therapeutic effect of anti-CD20/no-alpha mutein was accompanied by an expansion of peripheral central (TCM) and effector (TEM) memory CD8+ T cell compartments. Last, as opposed to IL-2, no-alpha mutein administered at the beginning of anti-CD20 treatment did not dampen the long-term protection of surviving mice after tumor rechallenge. Thus, this study shows that the combination of anti-tumor antibodies and no-alpha mutein is a promising approach to improve the therapeutic effect of these antibodies by potentiating NK/macrophage-mediated innate immunity and the adaptive T-cell response. |
| first_indexed | 2024-12-18T01:34:52Z |
| format | Article |
| id | doaj.art-3bcd9f905d40474e9def20f2e1f193b8 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-18T01:34:52Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-3bcd9f905d40474e9def20f2e1f193b82022-12-21T21:25:30ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2020.17705651770565A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapyAna Victoria Casadesús0Claire Deligne1Béré Kadjdiatou Diallo2Katya Sosa3Nathalie Josseaume4Circe Mesa5Kalet León6Tays Hernández7Jean-Luc Teillaud8Center of Molecular Immunology (CIM)University of OxfordUMRS 1135, Centre d’Immunologie Et Des Maladies Infectieuses Paris (Cimi-paris)Center of Molecular Immunology (CIM)Cordeliers Research CenterCenter of Molecular Immunology (CIM)Center of Molecular ImmunologyCenter of Molecular Immunology (CIM)UMRS 1135, Centre d’Immunologie Et Des Maladies Infectieuses Paris (Cimi-paris)Anti-CD20 treatment represents a therapeutic benefit for patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing patients. Among them, the combination of anti-CD20 and IL-2 that induces T cell response has been hampered by the expansion of FoxP3+ Tregs that strongly express the high affinity IL-2 receptor (IL-2R αβγ). We explore here the anti-tumor effect of an anti-CD20 antibody combined with a mutated IL-2 (no-alpha mutein) which has a disrupted affinity for the IL-2R αβγ. We demonstrate that anti-CD20/no-alpha mutein combination significantly augments the survival rate of mice challenged with huCD20+ cells as compared to animals treated with anti-CD20 ± IL-2. Moreover, the combination with no-alpha mutein but not IL-2 provokes an increase of granzyme B and perforin in splenic NK and CD8+ T cells, a reduction of Tregs and an increase in activated macrophages. The former combination also induces a T helper profile different from that obtained with IL-2, with an earlier polarization to Th1 and no increase in Th17. The therapeutic effect of anti-CD20/no-alpha mutein was accompanied by an expansion of peripheral central (TCM) and effector (TEM) memory CD8+ T cell compartments. Last, as opposed to IL-2, no-alpha mutein administered at the beginning of anti-CD20 treatment did not dampen the long-term protection of surviving mice after tumor rechallenge. Thus, this study shows that the combination of anti-tumor antibodies and no-alpha mutein is a promising approach to improve the therapeutic effect of these antibodies by potentiating NK/macrophage-mediated innate immunity and the adaptive T-cell response.http://dx.doi.org/10.1080/2162402X.2020.1770565anti-cd20il-2il-2 muteinimmunotherapylymphoma |
| spellingShingle | Ana Victoria Casadesús Claire Deligne Béré Kadjdiatou Diallo Katya Sosa Nathalie Josseaume Circe Mesa Kalet León Tays Hernández Jean-Luc Teillaud A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy OncoImmunology anti-cd20 il-2 il-2 mutein immunotherapy lymphoma |
| title | A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy |
| title_full | A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy |
| title_fullStr | A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy |
| title_full_unstemmed | A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy |
| title_short | A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy |
| title_sort | rationally engineered il 2 improves the antitumor effect of anti cd20 therapy |
| topic | anti-cd20 il-2 il-2 mutein immunotherapy lymphoma |
| url | http://dx.doi.org/10.1080/2162402X.2020.1770565 |
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