CRISPR-Cas – 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.

CAR-T therapy in acute and chronic leukemias: current applications and future outlooks

Anya Kerkache — Wed, 08 Mar 2023 10:35:19 +0000

John Gribben, MD, DSc, FRCP, FRCPath, FMed Sci, Barts Cancer Institute, London, UK, shares some insights into clinical indications for CAR-T therapy in acute and chronic leukemias, highlighting recent updates and challenges in this space. Prof. Gribben first discusses the role of CAR-T therapy in acute lymphoblastic leukemia (ALL), drawing focus on the two approved products in this malignancy. Prof. Gribben then goes on to explain mechanisms of resistance to CAR-T therapy in ALL, and ongoing research in this space. Following this, Prof. Gribben discusses updates and challenges with the use of CAR-T therapy in T-cell malignancies and acute myeloid leukemia (AML), and concludes by highlighting challenges with developing efficacious CAR-T products for chronic lymphocytic leukemia (CLL), which may be overcome by combining CAR-T cells with Bruton’s tyrosine kinase (BTK) inhibitors. 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.

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.

Addressing immunogenic barriers facing CRISPR-Cas9-based therapies

admin_vjr_user — Tue, 05 Apr 2022 15:59:59 +0000

Lena Peter, Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany, provides an overview of strategies to overcome immunogenic barriers in vivo CRISPR-Cas9-based treatments face. As humans have existing immunity to Cas9 of various bacterial strains, safety and efficacy may be affected when they are treated with gene therapies using modified Cas9 proteins. She also highlights the suppressive nature of Cas9-specific regulatory T cells (Tregs), which can inhibit production of effector T cells targeting Cas 9. However, the ratio of effector T cells and Tregs should be monitored in patients to assess safety. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.

Targeting WT1 peptides for TCR-based AML therapy

admin_vjr_user — Tue, 05 Apr 2022 13:27:40 +0000

Chiara Bonini, MD, Vita-Salute San Raffaele University & IRCCS San Raffaele Institute, Milan, Italy, describes research into the evaluation of Wilms’ tumor antigen 1 (WT1) as a candidate peptide for T cell receptor (TCR)-based cancer immunotherapies. Dr Bonini describes the screening of healthy donors for the presence of WT1-specific T cells and it was found that T cells specific for WT1 were present in the majority of donors tested. A high-avidity WT1-specific TCR that recognizes human leukocyte antigen class II (HLA-II) peptides was then selected using a funnel approach and ongoing research aims to evaluate the clinical potential of T cells engineered to express this TCR in the treatment of AML. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.

TCR redirected T cells for cancer therapy

admin_vjr_user — Tue, 05 Apr 2022 12:04:16 +0000

Chiara Bonini, MD, Vita-Salute San Raffaele University & IRCCS San Raffaele Institute, Milan, Italy, describes her research presented at the International Conference on Lymphocyte Engineering (ICLE) on multiple genome editing in T cells for cancer immunotherapy. Dr Bonini describes a strategy under investigation for the potential treatment of acute myeloid leukemia (AML), which involves the knockout of two genes encoding the alpha-beta chain of the endogenous T cell receptor (TCR) in lymphocytes, followed by substitution with a tumor-specific TCR that recognizes cancer cells. Ongoing research is being performed to evaluate similar approaches in other types of cancer. This interview took place at ICLE 2022.

Applying CRISPR-Cas technology in advancing autologous T-cell therapies

Simon Ng — Mon, 04 Apr 2022 09:59:20 +0000

Crispr-Cas9 technology as a gene editing tool has enabled the knockout of various inhibitory and endogenous T-cell receptors in the allogeneic setting. Mateusz Legut, PhD, New York Genome Center, New York, NY, describes issues with using Crispr-Cas9 in developing autologous T-cell therapies, including various editing efficiencies, off-targets and chromosomal abnormalities. Dr Legut additionally highlights research using lentiviral vector-mediated overexpression to screen the genome for novel genes that are potentially beneficial for T-cell therapies. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.”

Development and applications of OverCITE-seq

Simon Ng — Mon, 04 Apr 2022 09:59:19 +0000

Mateusz Legut, PhD, New York Genome Center, New York, NY, provides an overview of the single-cell genomics method OverCITE-seq and its role in improving next-generation T cell therapies. Initial iterations of single-cell phenotyping technology came in the form CITE-seq, which enabled simultaneous RNA sequencing and measurement of surface protein levels, as well as ECCITE-seq, which utilizes CRISPR screens to assess changes in the transcriptome. OverCITE-seq, the third generation of single-cell genomics technology, measures levels of overexpressed genes and their effect on T-cells. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.

The use of CRISPR-Cas9 technology in the development of T cell therapies

admin_vjr_user — Fri, 01 Apr 2022 12:36:55 +0000

Alessio Nahmad, PhD, Tel Aviv University, Tel Aviv, Israel, describes the role and applications of CRISPR-Cas9-based genome editing in the development of CAR T-cell and T cell receptor (TCR) therapies. The aim is often to ablate specific genes that can reduce efficiency of the T cell product such the TCR genes. For example, ablating TCR genes can improve efficiency and reduce toxicity. In addition, ablating certain genes, such as PD-1, can reduce cellular exhaustion. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.