ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells
Despite recent advances in immunotherapies targeting single tumor-associated antigens, patients with multiple myeloma eventually relapse. ISB 2001 is a CD3+ T cell engager (TCE) co-targeting BCMA and CD38 designed to improve cytotoxicity against multiple myeloma. Targeting of two tumor-associated an...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2024
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| _version_ | 1817931147036852224 |
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| author | Carretero-Iglesia, L Hall, OJ Berret, J Pais, D Estoppey, C Chimen, M Monney, T Loyau, J Dreyfus, C Macoin, J Perez, C Menon, V Gruber, I Laurendon, A Caro, LN Gudi, GS Matsuura, T van der Graaf, PH Blein, S Mbow, ML Croasdale-Wood, R Srivastava, A Dyson, MR Matthes, T Kaya, Z Edwards, CM Edwards, JR |
| author_facet | Carretero-Iglesia, L Hall, OJ Berret, J Pais, D Estoppey, C Chimen, M Monney, T Loyau, J Dreyfus, C Macoin, J Perez, C Menon, V Gruber, I Laurendon, A Caro, LN Gudi, GS Matsuura, T van der Graaf, PH Blein, S Mbow, ML Croasdale-Wood, R Srivastava, A Dyson, MR Matthes, T Kaya, Z Edwards, CM Edwards, JR |
| author_sort | Carretero-Iglesia, L |
| collection | OXFORD |
| description | Despite recent advances in immunotherapies targeting single tumor-associated antigens, patients with multiple myeloma eventually relapse. ISB 2001 is a CD3+ T cell engager (TCE) co-targeting BCMA and CD38 designed to improve cytotoxicity against multiple myeloma. Targeting of two tumor-associated antigens by a single TCE resulted in superior cytotoxic potency across a variable range of BCMA and CD38 tumor expression profiles mimicking natural tumor heterogeneity, improved resistance to competing soluble factors and exhibited superior cytotoxic potency on patient-derived samples and in mouse models. Despite the broad expression of CD38 across human tissues, ISB 2001 demonstrated a reduced T cell activation profile in the absence of tumor cells when compared to TCEs targeting CD38 only. To determine an optimal first-in-human dose for the ongoing clinical trial (NCT05862012), we developed an innovative quantitative systems pharmacology model leveraging preclinical data, using a minimum pharmacologically active dose approach, therefore reducing patient exposure to subefficacious doses of therapies. |
| first_indexed | 2024-12-09T03:17:23Z |
| format | Journal article |
| id | oxford-uuid:c3622b6e-528d-4447-a487-c45f54ddb9e6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:17:23Z |
| publishDate | 2024 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:c3622b6e-528d-4447-a487-c45f54ddb9e62024-10-24T20:37:14ZISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c3622b6e-528d-4447-a487-c45f54ddb9e6EnglishJisc Publications RouterNature Research2024Carretero-Iglesia, LHall, OJBerret, JPais, DEstoppey, CChimen, MMonney, TLoyau, JDreyfus, CMacoin, JPerez, CMenon, VGruber, ILaurendon, ACaro, LNGudi, GSMatsuura, Tvan der Graaf, PHBlein, SMbow, MLCroasdale-Wood, RSrivastava, ADyson, MRMatthes, TKaya, ZEdwards, CMEdwards, JRDespite recent advances in immunotherapies targeting single tumor-associated antigens, patients with multiple myeloma eventually relapse. ISB 2001 is a CD3+ T cell engager (TCE) co-targeting BCMA and CD38 designed to improve cytotoxicity against multiple myeloma. Targeting of two tumor-associated antigens by a single TCE resulted in superior cytotoxic potency across a variable range of BCMA and CD38 tumor expression profiles mimicking natural tumor heterogeneity, improved resistance to competing soluble factors and exhibited superior cytotoxic potency on patient-derived samples and in mouse models. Despite the broad expression of CD38 across human tissues, ISB 2001 demonstrated a reduced T cell activation profile in the absence of tumor cells when compared to TCEs targeting CD38 only. To determine an optimal first-in-human dose for the ongoing clinical trial (NCT05862012), we developed an innovative quantitative systems pharmacology model leveraging preclinical data, using a minimum pharmacologically active dose approach, therefore reducing patient exposure to subefficacious doses of therapies. |
| spellingShingle | Carretero-Iglesia, L Hall, OJ Berret, J Pais, D Estoppey, C Chimen, M Monney, T Loyau, J Dreyfus, C Macoin, J Perez, C Menon, V Gruber, I Laurendon, A Caro, LN Gudi, GS Matsuura, T van der Graaf, PH Blein, S Mbow, ML Croasdale-Wood, R Srivastava, A Dyson, MR Matthes, T Kaya, Z Edwards, CM Edwards, JR ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells |
| title | ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells |
| title_full | ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells |
| title_fullStr | ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells |
| title_full_unstemmed | ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells |
| title_short | ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells |
| title_sort | isb 2001 trispecific t cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells |
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