Allogeneic Therapy – VJRegenMed

CD33 CRISPR/Cas9 gene-edited donor allograft in patients with AML at risk of relapse post-HSCT

Anya Kerkache — Thu, 09 Mar 2023 11:31:49 +0000

John DiPersio, MD, PhD, Washington University School of Medicine, St. Louis, MO, shares the rationale and results of a first-in-human clinical trial evaluating the safety of trem-cel (formerly VOR33), a CD33 CRISPR/Cas9 gene-edited donor allograft designed to prevent relapse in patients with acute myeloid leukemia (AML) undergoing hematopoietic stem cell transplantation (HSCT; NCT04849910). Results from the first two patients transplanted with trem-cel indicated neutrophil engraftment and a similar platelet recovery when compared to patients who received non-edited CD34-selected grafts. Treatment with gemtuzumab ozogamicin (GO) in one of the recipients did not result in a change in blood counts, suggesting that the target was effectively eliminated on the recipient’s stem cells and that GO would then only target residual leukemia cells expressing CD33. The ability of this strategy to induce long-term remission and to effectively eliminate all residual leukemia cells remains to be confirmed. This interview took place at the 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR® held in Orlando, FL.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

Exploring the potential role of CD7-targeting CAR-T cells in T-ALL

Anya Kerkache — Wed, 08 Mar 2023 10:35:18 +0000

Maksim Mamonkin, PhD, Baylor College of Medicine, Houston, TX, shares some insights into the promise of CD7-targeting CAR-T therapies for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL). Dr Mamonkin explains methods used to develop these products, and further highlights the promising activity that has been observed in ongoing clinical trials. This interview took place at the EBMT-EHA 5th European CAR T-cell Meeting held in Rotterdam, The Netherlands.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

CARBON trial: investigating CTX110 allogeneic CRISPR-Cas9–engineered CAR-Ts in R/R LBCL

Anya Kerkache — Thu, 26 Jan 2023 12:11:30 +0000

Constantine Tam, MBBS (Hons), MD, FRACP, FRCPA, Peter MacCallum Cancer Centre, St. Vincent’s Hospital, University of Melbourne, Melbourne, Australia, reports results from the CARBON Phase I dose-escalation study (NCT04035434), testing the safety and efficacy of a novel allogeneic CRISPR-Cas9-engineered CAR-T product, CTX110, in heavily pre-treated patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The study reported that the CAR-Ts showed clinical activity with the ability to expand in the body, and a low risk of graft-versus-host disease (GvHD). This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

The safety and efficacy of UCART123v1.2 in R/R AML: results from AMELI-01

Anya Kerkache — Thu, 26 Jan 2023 12:11:29 +0000

David Sallman, MD, Moffitt Cancer Center, Tampa, FL, discusses the results of the AMELI-01 Phase I trial of UCART123v1.2 in adult patients with relapsed refractory (R/R) CD123+ acute myeloid leukemia (AML; NCT04106076). UCART123v1.2 is an anti-CD123 allogeneic CAR-T product, that has been genetically modified to minimize the occurrence of graft-versus-host disease (GvHD). Overall, results suggest UCART123v1.2 is well tolerated, though severe cytokine release syndrome (CRS) did occur, and that three-drug lymphodepletion optimizes CAR-T expansion and patient responses. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

CYP-001 in adults with steroid-resistant GvHD

Simon Ng — Tue, 03 May 2022 16:17:07 +0000

Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) have shown promising efficacy as a cell therapy. Ross Macdonald, PhD, Cynata Therapeutics, Melbourne, Australia, discusses results from a Phase I trial (NCT02923375) assessing CYP-001, a MSC-based cell therapy in patients with steroid resistant graft-versus-host disease (GvHD). For patients who progress from corticosteroids, treatment options remain poor and mortality remains high. CYP-001 resulted in a complete response in over half of the cohort and after a two year follow-up, a survival rate of over 50% was reported. This interview was conducted during Meeting on the Mediterranean 2022.

SCUlpTOR: CYP-004 in osteoarthritis

Simon Ng — Tue, 03 May 2022 16:17:06 +0000

Ross Macdonald, PhD, Cynata Therapeutics, Melbourne, Australia, discusses the Phase III SCUlpTOR trial (ACTRN12620000870954) assessing CYP-004, a novel mesenchymal stem cell (MSCs)-based cell therapy for patients with osteoarthritis. Whilst previous studies investigating autologous stem cell therapies have shown promise, there is an unmet need for curative therapies. The randomized double blind trial will assess the investigational therapy in 440 patients with degenerative osteoarthritis. The interview was conducted during Meeting on the Mediterranean 2022.

Addressing challenges in using MSCs in cell therapies

Simon Ng — Thu, 21 Apr 2022 15:04:28 +0000

Mesenchymal stem cells (MSCs) have demonstrated potential in cell therapies, as they have unique immunomodulatory properties. Ross Macdonald, PhD, Cynata Therapeutics, Melbourne, Australia, comments on the hurdles in commercializing MSC-based cell therapies. Unlike autologous chimeric antigen receptor (CAR) T-cell therapies, MSCs are derived from allogeneic sources, which in itself presents logistical issues in terms of obtaining enough donors. Cell expansion for commercial usage additionally is an issue, as MSCs become less potent as they expand, and Dr Macdonald presents solutions offered by Cynata Therapeutics that attempt to overcome the aforementioned barriers. This interview was conducted during Meeting on the Mediterranean 2022.

Generating iSPC-derived MSCs with the Cymerus™ Platform

Simon Ng — Thu, 21 Apr 2022 15:04:27 +0000

Ross Macdonald, PhD, Cynata Therapeutics, Melbourne, Australia, discusses the process of manufacturing mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) with the Cymerus Platform. MSCs have shown encouraging efficacy as cell therapies and using iPSCs enables the MSCs to remain potent, as they do not require expansion. The iSPCs also do not require multiple donors as they can replicate indefinitely, resulting in MSCs of a consistent quality. This interview was conducted during Meeting on the Mediterranean 2022.

Optimizing the upscaling and outscaling of CAR T-cell therapies

Simon Ng — Thu, 14 Apr 2022 15:56:43 +0000

Saskia Rösch, PhD, Miltenyi Biotec, Bergisch Gladbach, Germany, describes novel approaches to enhance chimeric antigen receptor (CAR) T-cell manufacturing. Upscaling can incur cost-related barriers, especially for T-cell receptor (TCR) and allogeneic therapies in solid tumor indications, and utilizing non-viral vectors as well as reducing the cultivation time may ameliorate the aforementioned issues. Developers additionally face issues in outscaling due to complications in material and documentation management, and Dr Rösch suggests decentralization as a potential solution. Regulatory authorities must also collaborate to expedite the development of T-cell therapies. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.

Adoptive T-cell therapy for immunosuppressed patients with COVID-19

admin_vjr_user — Tue, 05 Apr 2022 16:00:01 +0000

Patients who receive immunosuppressants as a result of organ or hematopoietic stem-cell transplantation are more susceptible to COVID-19 infection and may not benefit from current COVID-19 vaccines. Lena Peter, Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany, describes treating COVID-19 in immunocompromised patients with adoptive T-cell therapy. T-cells derived from donors were isolated and were made resistant to tacrolimus, a common immunosuppressant, via knockout of the gene encoding FKBP12. In vivo studies determined the modified T-cells to effectively target COVID-19 and its variants, and Phase 1 are currently being planned to assess the novel approach. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.