- |||||||||| ECT-001-CB / ExCellThera
Trial completion date, Trial primary completion date: US Study of UM171-Expanded CB in Patients With High Risk Leukemia/Myelodysplasia (clinicaltrials.gov) - Jun 29, 2023
P2, N=30, Recruiting,
Compared to real-world evidence with CB and MUD alloHCT, this study suggests that UM171-expanded CB recipients may benefit from lower NRM and higher GRFS. Trial completion date: Jun 2024 --> Sep 2025 | Trial primary completion date: Jun 2023 --> Sep 2023
- |||||||||| ECT-001-CB / ExCellThera
Enrollment change, Trial completion date, Trial primary completion date: US Study of UM171-Expanded CB in Patients With High Risk Leukemia/Myelodysplasia (clinicaltrials.gov) - Jan 6, 2023
P2, N=30, Recruiting,
Trial completion date: Apr 2024 --> Jul 2025 | Trial primary completion date: Apr 2023 --> Jul 2023 N=20 --> 30 | Trial completion date: Dec 2022 --> Jun 2024 | Trial primary completion date: Jun 2022 --> Jun 2023
- |||||||||| ECT-001-CB / ExCellThera
Improved Outcomes of UM171-Expanded Cord Blood Transplantation Compared with Other Graft Sources: Real World Evidence (ENMCC - 220-222) - Nov 4, 2022 - Abstract #ASH2022ASH_3715;
While this study was limited by the small number of UM171 CB trial participants and inability to identify the planned number of controls for each case, UM171 expansion of CB appeared to achieve the desired outcome of maintaining CB’s benefits while removing its disadvantages. Thus, prospective randomized studies of UM171-expanded CBT compared to MUD PBSC alloHCT are warranted to confirm these results.
- |||||||||| ECT-001-CB / ExCellThera
Preclinical, Journal: Update on preclinical and clinical efforts on ex-vivo expansion of hematopoietic stem and progenitor cells. (Pubmed Central) - Jul 9, 2022
Thus, prospective randomized studies of UM171-expanded CBT compared to MUD PBSC alloHCT are warranted to confirm these results. Preliminary data from multiple phase I/II clinical trials regarding transplants of ex-vivo-expanded HSCs and HPCs have demonstrated that ex-vivo expansion may be used to overcome the limitation of the rarity of HSCs without compromising stemness.
- |||||||||| ECT-001-CB / ExCellThera
Journal: UM171 expansion of cord blood improves donor availability and HLA matching for all patients, including minorities. (Pubmed Central) - Jul 8, 2022
In this study, we retrospectively performed HLA matching simulations to assess how the minimal cell content requirements associated with UM171 CB expansion may improve usability of existing CB unit inventories and donor availability for patients of different races and ethnicities...UM171 raises this proportion to 53.8% and 20.2%, respectively, making CB banks potentially more cost-effective. In conclusion, UM171 expansion allows the use of smaller CB units while also improving access to transplantation for racial and ethnic minorities.
- |||||||||| ECT-001-CB / ExCellThera
Enrollment change, Trial withdrawal: US Phase I Study of ECT-001-CB in Patients With Sickle-Cell Disease (clinicaltrials.gov) - Jul 5, 2022
P1, N=0, Withdrawn,
In conclusion, UM171 expansion allows the use of smaller CB units while also improving access to transplantation for racial and ethnic minorities. N=12 --> 0 | Recruiting --> Withdrawn
- |||||||||| ECT-001-CB / ExCellThera
Trial completion date, Trial primary completion date: ECT-001 (UM171) Expanded Cord Blood Transplant to Treat High-risk Multiple Myeloma (clinicaltrials.gov) - Jan 14, 2022
P1/2, N=20, Recruiting,
We are currently studying the antileukemia effect of UM171 CB in very high risk acute leukemias. Trial completion date: Mar 2024 --> Sep 2025 | Trial primary completion date: Mar 2022 --> Sep 2021
- |||||||||| ECT-001 / ExCellThera
[VIRTUAL] ENGRAFTMENT POTENTIAL OF CD34+ CELLS FROM SEVERE APLASTIC ANEMIA PATIENTS EXPANDED WITH UM171 () - Oct 27, 2021 - Abstract #HEMO2021HEMO_1330;
More recently, the addition of eltrombopag showed that the expansion of hematopoietic precursors is a therapeutic alternative...The conditioning regimen consisted of two intraperitoneal injections of 12.5 mg/kg busulfan administered 48 and 24 hours before transplantation...More replicates (patients and controls) are required to firmly establish the benefit of UM171 in conferring repopulation potential to ex vivo expanded CD34+ cells from AA patients.Conclusion In initial experiments, in vitro treatment with UM171 appears to increase the engraftment of CD34+ cells isolated from UCB and from the BM of immune AA patients. These Results need to be confirmed in additional experiments.
- |||||||||| ECT-001 / ExCellThera
[VIRTUAL] In vivo and in vitro optimization of protocols for the expansion of geneticallyengineered human hematopoietic stem and progenitor cells () - Oct 2, 2021 - Abstract #ESGCT2021ESGCT_598;
We first evaluated 2 HSC agonists, UM171 and SR1, and found that combination of both maintained the highest engraftment capacity of mPB CD34+ cells in NSG mice, with a particular benefit on shortterm (ST) engraftment as compared to UM171 alone...Preliminary results suggest the possibility to implement new base editor technology in our optimized expansion protocol. In conclusion, we present a revisited expansion protocol based on clinically validated compounds and tailored to geneticallyengineered mPB HSC, towards harnessing the full potential of ex vivo HSC expansion in the gene therapy context.
- |||||||||| ECT-001 / ExCellThera, Mozobil (plerixafor) / Sanofi
[VIRTUAL] High throughput characterization of CD34+ cell states and dynamics upon genetic engineering () - Oct 2, 2021 - Abstract #ESGCT2021ESGCT_568;
We then investigated the cell states over 7 days of expansion in 191,980 single cells from bulk HSPCs and FACSsorted hematopoietic stem cells (HSC), unveiling potential early effects of the HSCagonist UM171 on CD34+ cells priming, differentiation, and vector insertion site (IS) distribution (94,362 unique IS). To our knowledge, our analytical platform represents the most comprehensive transcriptional characterization of CD34+ cells upon genetic engineering and may provide a long needed stepchange in the characterization of GT DP.
- |||||||||| ECT-001 / ExCellThera
[VIRTUAL] Targeting CD34 + Hematopoietic Stem cells: a potential promise for Hemophilia A () - Oct 2, 2021 - Abstract #ESGCT2021ESGCT_394;
Interestingly, we could follow through timelapse video analyses the dynamics of engraftment and spatial relationships of CD34 + with endothelial cells, and quantify their invivo expansion. In conclusion, human CD34 + treated with UM171 can successfully be transduced with an LVcarryingFVIII transgene and show abundant invivo engraftment, potentially serving as GT target in HA.
- |||||||||| ECT-001-CB / ExCellThera
Enrollment open: US Phase I Study of ECT-001-CB in Patients With Sickle-Cell Disease (clinicaltrials.gov) - Jul 19, 2021
P1, N=12, Recruiting,
UM171-expanded grafts offer a valuable option for patients with aplastic anemia in need of transplantation but have no suitable donor. Not yet recruiting --> Recruiting
- |||||||||| ECT-001 / ExCellThera
Preclinical, Review, Journal: Mechanistic Basis of ex Vivo Umbilical Cord Blood Stem Progenitor Cell Expansion. (Pubmed Central) - Jun 3, 2021
We also review recent clinical research on small molecules (StemRegenin-1, UM171, and nicotinamide) in ex vivo expanded CB and discuss yet unvalidated preclinical strategies...Greater knowledge of optimal ex vivo expansion strategies, cell longevity, and graft potency will expand the scope of cellular therapies. Also the development of adequate ex vivo HSPC expansion strategies could bring expanded cord blood grafts to the forefront of transplant therapy and regenerative medicine.
- |||||||||| ECT-001 / ExCellThera
Journal: Expanded circulating hematopoietic stem/progenitor cells as novel cell source for the treatment of TCIRG1 osteopetrosis. (Pubmed Central) - May 22, 2021
To overcome the limit of bone marrow harvest/ HSPC mobilization and serial blood drawings in TCIRG1 patients, we applied UM171-based ex-vivo expansion of HSPCs coupled with lentiviral gene transfer...Moreover, when CD34+ cells were differentiated in vitro, genetically corrected osteoclasts resorbed the bone efficiently. Overall, we provide evidence that expansion of circulating HSPCs coupled to gene therapy can overcome the limit of stem cell harvest in osteopetrotic patients, thus opening the way to future gene-based treatment of skeletal diseases caused by bone marrow fibrosis.
- |||||||||| ECT-001-CB / ExCellThera
Trial initiation date: US Phase I Study of ECT-001-CB in Patients With Sickle-Cell Disease (clinicaltrials.gov) - Apr 29, 2021
P1, N=12, Not yet recruiting,
CRL3 targets components of the LSD1/RCOR1 corepressor complex for proteasomal degradation, hence re-establishing H3K4me2 and H3K27ac epigenetic marks, which are rapidly decreased upon ex vivo culture of human HSCs. Initiation date: Mar 2021 --> Jun 2021
- |||||||||| ECT-001-CB / ExCellThera
Trial initiation date: US Phase I Study of ECT-001-CB in Patients With Sickle-Cell Disease (clinicaltrials.gov) - Feb 2, 2021
P1, N=12, Not yet recruiting,
Taken together, LSD1 and CoREST restrict HSC expansion, and are principal targets of UM171, forming a mechanistic basis for the HSC promoting activity of UM171. Initiation date: Dec 2020 --> Mar 2021
- |||||||||| ECT-001 / ExCellThera
[VIRTUAL] Accessible Source of Stem Cells: Expansion of CD34+ Cells in Bulk Peripheral Blood Mononuclear Cells Using UM171 (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2825;
The advantage of expanding HPSCs in bulk is to preserve the rare naïve CD34+ population that can be lost during the immunoselection process and to take advantage of the myeloid niche, to further enhance the expansion along with UM171. This expansion approach can be performed at larger scale on the buffy coats often dismissed in blood banks to provide considerable number of CD34+ cells for either banking, research or future clinical application.
- |||||||||| ECT-001 / ExCellThera
[VIRTUAL] Long-Term Expansion of Human Hematopoietic Stem/Progenitor Cells in Cytokine-Free Conditions (Channel 6 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_1592;
In conclusion, we have developed a long-term expansion culture system for human HSCs without recombinant cytokines or albumin. the culture system described here provides a powerful platform for both basic scientists and clinicians interested in stem cell biology, leukemia therapeutics, and the next generation of HSC transplantation and gene therapies.
- |||||||||| ECT-001 / ExCellThera
Journal: UM171 expands distinct types of myeloid and NK progenitors from human pluripotent stem cells. (Pubmed Central) - Oct 25, 2020
In contrast, in lymphoid cultures on OP9-DLL4, in the presence of SCF, FLT3L, and IL7, UM171 selectively expanded CD34CD45CD7 lymphoid progenitors with NK cell potential, and increased NK cell output up to 10-fold. These studies should improve our understanding of the effect of UM171 on de novo generated HPs, and facilitate development of protocols for robust granulocyte and lymphoid cell production from hPSCs, for adoptive immunotherapies.
- |||||||||| ECT-001 / ExCellThera, fenretinide (RT-101) / ReVision Therapeutics
Journal: Sphingolipid Modulation Activates Proteostasis Programs to Govern Human Hematopoietic Stem Cell Self-Renewal. (Pubmed Central) - Sep 10, 2020
Inhibition of DEGS1 in hematopoietic stem and progenitor cells during the transition from quiescence to cellular activation with N-(4-hydroxyphenyl) retinamide activates coordinated stress pathways that coalesce on endoplasmic reticulum stress and autophagy programs to maintain immunophenotypic and functional HSCs. Thus, our work identifies a linkage between sphingolipid metabolism, proteostatic quality control systems, and HSC self-renewal and provides therapeutic targets for improving HSC-based cellular therapeutics.
- |||||||||| ECT-001 / ExCellThera
Journal: Integrin-α3 Is a Functional Marker of Ex Vivo Expanded Human Long-Term Hematopoietic Stem Cells. (Pubmed Central) - Aug 27, 2020
Exploiting the pyrimidoindole derivative UM171 to expand cord blood (CB) cells, we show that ITGA3 expression is sufficient to separate the primitive EPCRCD90CD133CD34CD45RA HSC population into two functionally distinct fractions presenting mostly short-term (ITGA3) and both short-term and long-term (ITGA3) repopulating potential...Moreover, ITGA3 expression is functionally required for the long-term engraftment of CB cells. Altogether, our results indicate that ITGA3 is a reliable marker of cultured human long-term repopulating HSCs (LT-HSCs) and represents an important tool to improve the accuracy of prospective HSC identification in culture.
- |||||||||| ECT-001 / ExCellThera, Amnolake (retinobenzoic acid) / TMRC, Syros, Nippon Shinyaku, CytRx, Zeria
Journal: Effective and Rapid Generation of Functional Neutrophils from Induced Pluripotent Stem Cells Using ETV2-Modified mRNA. (Pubmed Central) - Jul 2, 2020
Neutrophils obtained in these conditions displayed a typical somatic neutrophil morphology, produced reactive oxygen species, formed neutrophil extracellular traps and possessed phagocytic and chemotactic activities. Overall, this technology offers an opportunity to generate a significant number of neutrophils as soon as 14 days after initiation of differentiation.
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