ORCID Profile
0000-0003-2091-7927
Current Organisations
Hôpital Saint-Louis
,
Hospital for Sick Children
,
Université Paris Descartes
,
Université Paris Diderot
,
Université Paris Cité
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Publications
Supplementary Data Tables from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 31-07-2023
DOI: 10.1158/2159-8290.23807943
Abstract: Supplementary Table S1. Bridging chemotherapies by ATC class and preferred term (safety set) Supplementary Table S2. Lymphodepleting chemotherapies (safety set) Supplementary Table S3. Cytokine release syndrome following YTB323 infusion Supplementary Table S4. Neurological adverse reactions following YTB323 infusion Supplementary Table S5. Summary of cellular kinetic parameters in peripheral blood by flow cytometry for YTB323 at DL1 and DL2 Supplementary Table S6. Summary of cellular kinetic parameters in peripheral blood by flow cytometry and qPCR for YTB323 at DL1 and DL2.
Data from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 06-09-2023
Supplementary Data Figures from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 06-09-2023
Data from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 06-09-2023
DOI: 10.1158/2159-8290.C.6767337
Abstract: Abstract CAR T-cell product quality and stemness (T sub stem /sub ) are major determinants of i in vivo /i expansion, efficacy, and clinical response. Prolonged i ex vivo /i culturing is known to deplete T sub stem /sub , affecting clinical outcome. YTB323, a novel autologous CD19-directed CAR T-cell therapy expressing the same validated CAR as tisagenlecleucel, is manufactured using a next-generation platform in days. Here, we report the preclinical development and preliminary clinical data of YTB323 in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL NCT03960840). In preclinical mouse models, YTB323 exhibited enhanced i in vivo /i expansion and antitumor activity at lower doses than traditionally manufactured CAR T cells. Clinically, at doses 25-fold lower than tisagenlecleucel, YTB323 showed (i) promising overall safety [cytokine release syndrome (any grade, 35% grade ≥3, 6%), neurotoxicity (any grade, 25% grade ≥3, 6%)] (ii) overall response rates of 75% and 80% for DL1 and DL2, respectively (iii) comparable CAR T-cell expansion and (iv) preservation of T-cell phenotype. Current data support the continued development of YTB323 for r/r DLBCL. Significance: Traditional CAR T-cell manufacturing requires extended i ex vivo /i cell culture, reducing naive and stem cell memory T-cell populations and diminishing antitumor activity. YTB323, which expresses the same validated CAR as tisagenlecleucel, can be manufactured in days while retaining T-cell stemness and enhancing clinical activity at a 25-fold lower dose. /
Supplementary Data Figures from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 31-07-2023
DOI: 10.1158/2159-8290.23807946
Abstract: Supplementary Fig. S1. Preclinical evaluation and characterization of YTB323 and CTL*019 for Donor 2 and 3 Supplementary Fig. S2. Differential gene expression of CTL*019 cells versus YTB323 cells (preclinical) Supplementary Fig. S3. Preclinical validation of YTB323 Supplementary Fig. S4. Dose-dependent expansion (Cmax and AUC0-21d) of YTB323 and CTL*019 in NSG mice with NALM6 Supplementary Fig. S5. CD4:CD8 ratio comparison of leukapheresis and cell products of YTB323 and tisagenlecleucel Supplementary Fig. S6. Stemness and memory differentiation gene signatures are retained or enriched for in YTB323 final product Supplementary Fig. S7. Differential gene expression of tisagenlecleucel versus YTB323 final product Supplementary Fig. S8. Naive/TSCM cells and a naive stem-like gene signature correlate with higher expansion and a better response Supplementary Fig. S9. T-cell subset and checkpoint inhibitor analysis by flow cytometry on PBMCs collected post-YTB323 infusion Supplementary Fig. S10. Pre-clinical T-cell gating strategies.
Supplementary Data Figures from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 06-09-2023
Supplementary Data Tables from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 06-09-2023
Clonal hematopoiesis driven by chromosome 1q/MDM4 trisomy defines a canonical route toward leukemia in Fanconi anemia
Publisher: Elsevier BV
Date: 02-2023
Concurrent CDX2 cis-deregulation and UBTF::ATXN7L3 fusion define a novel high-risk subtype of B-cell ALL
Publisher: American Society of Hematology
Date: 16-06-2022
Abstract: Oncogenic alterations underlying B-cell acute lymphoblastic leukemia (B-ALL) in adults remain incompletely elucidated. To uncover novel oncogenic drivers, we performed RNA sequencing and whole-genome analyses in a large cohort of unresolved B-ALL. We identified a novel subtype characterized by a distinct gene expression signature and the unique association of 2 genomic microdeletions. The 17q21.31 microdeletion resulted in a UBTF::ATXN7L3 fusion transcript encoding a chimeric protein. The 13q12.2 deletion resulted in monoallelic ectopic expression of the homeobox transcription factor CDX2, located 138 kb in cis from the deletion. Using 4C-sequencing and CRISPR interference experiments, we elucidated the mechanism of CDX2 cis-deregulation, involving PAN3 enhancer hijacking. CDX2/UBTF ALL (n = 26) harbored a distinct pattern of additional alterations including 1q gain and CXCR4 activating mutations. Within adult patients with Ph− B-ALL enrolled in GRAALL trials, patients with CDX2/UBTF ALL (n = 17/723, 2.4%) were young (median age, 31 years) and dramatically enriched in females (male/female ratio, 0.2, P = .002). They commonly presented with a pro-B phenotype ALL and moderate blast cell infiltration. They had poor response to treatment including a higher risk of failure to first induction course (19% vs 3%, P = .017) and higher post-induction minimal residual disease (MRD) levels (MRD ≥ 10−4, 93% vs 46%, P & .001). This early resistance to treatment translated into a significantly higher cumulative incidence of relapse (75.0% vs 32.4%, P = .004) in univariate and multivariate analyses. In conclusion, we discovered a novel B-ALL entity defined by the unique combination of CDX2 cis-deregulation and UBTF::ATXN7L3 fusion, representing a high-risk disease in young adults.
Supplementary Data Tables from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 06-09-2023
A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 30-05-2023
DOI: 10.1158/2159-8290.CD-22-1276
Abstract: Traditional CAR T-cell manufacturing requires extended ex vivo cell culture, reducing naive and stem cell memory T-cell populations and diminishing antitumor activity. YTB323, which expresses the same validated CAR as tisagenlecleucel, can be manufactured in & days while retaining T-cell stemness and enhancing clinical activity at a 25-fold lower dose.
Supplementary Data Figures from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 31-07-2023
DOI: 10.1158/2159-8290.23807946.V1
Abstract: Supplementary Fig. S1. Preclinical evaluation and characterization of YTB323 and CTL*019 for Donor 2 and 3 Supplementary Fig. S2. Differential gene expression of CTL*019 cells versus YTB323 cells (preclinical) Supplementary Fig. S3. Preclinical validation of YTB323 Supplementary Fig. S4. Dose-dependent expansion (Cmax and AUC0-21d) of YTB323 and CTL*019 in NSG mice with NALM6 Supplementary Fig. S5. CD4:CD8 ratio comparison of leukapheresis and cell products of YTB323 and tisagenlecleucel Supplementary Fig. S6. Stemness and memory differentiation gene signatures are retained or enriched for in YTB323 final product Supplementary Fig. S7. Differential gene expression of tisagenlecleucel versus YTB323 final product Supplementary Fig. S8. Naive/TSCM cells and a naive stem-like gene signature correlate with higher expansion and a better response Supplementary Fig. S9. T-cell subset and checkpoint inhibitor analysis by flow cytometry on PBMCs collected post-YTB323 infusion Supplementary Fig. S10. Pre-clinical T-cell gating strategies.
Supplementary Data Tables from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 31-07-2023
DOI: 10.1158/2159-8290.23807943.V1
Abstract: Supplementary Table S1. Bridging chemotherapies by ATC class and preferred term (safety set) Supplementary Table S2. Lymphodepleting chemotherapies (safety set) Supplementary Table S3. Cytokine release syndrome following YTB323 infusion Supplementary Table S4. Neurological adverse reactions following YTB323 infusion Supplementary Table S5. Summary of cellular kinetic parameters in peripheral blood by flow cytometry for YTB323 at DL1 and DL2 Supplementary Table S6. Summary of cellular kinetic parameters in peripheral blood by flow cytometry and qPCR for YTB323 at DL1 and DL2.
Data from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Publisher: American Association for Cancer Research (AACR)
Date: 31-07-2023
DOI: 10.1158/2159-8290.C.6767337.V1
Abstract: Abstract CAR T-cell product quality and stemness (T sub stem /sub ) are major determinants of i in vivo /i expansion, efficacy, and clinical response. Prolonged i ex vivo /i culturing is known to deplete T sub stem /sub , affecting clinical outcome. YTB323, a novel autologous CD19-directed CAR T-cell therapy expressing the same validated CAR as tisagenlecleucel, is manufactured using a next-generation platform in days. Here, we report the preclinical development and preliminary clinical data of YTB323 in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL NCT03960840). In preclinical mouse models, YTB323 exhibited enhanced i in vivo /i expansion and antitumor activity at lower doses than traditionally manufactured CAR T cells. Clinically, at doses 25-fold lower than tisagenlecleucel, YTB323 showed (i) promising overall safety [cytokine release syndrome (any grade, 35% grade ≥3, 6%), neurotoxicity (any grade, 25% grade ≥3, 6%)] (ii) overall response rates of 75% and 80% for DL1 and DL2, respectively (iii) comparable CAR T-cell expansion and (iv) preservation of T-cell phenotype. Current data support the continued development of YTB323 for r/r DLBCL. Significance: Traditional CAR T-cell manufacturing requires extended i ex vivo /i cell culture, reducing naive and stem cell memory T-cell populations and diminishing antitumor activity. YTB323, which expresses the same validated CAR as tisagenlecleucel, can be manufactured in days while retaining T-cell stemness and enhancing clinical activity at a 25-fold lower dose. /
Related Organisations
Related Funding Activities
No related grants have been discovered for Nicolas Boissel.