Genome Editing – 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.

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.

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.

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.

Overexpression of the LBTR gene to optimize T cell proliferation

Simon Ng — Thu, 31 Mar 2022 17:49:28 +0000

Mateusz Legut, PhD, New York Genome Center, New York, NY, discusses strategies to improve the efficacy of T-cells in adoptive cell therapies. Certain genes that are not typically expressed in T-cells such as the lymphotoxin beta receptor (LTBR) gene were identified via CRISPR-based analysis of the whole human genome. Overexpression of the gene led to improved cell quality without affecting functionality of the T-cells and Dr Legut emphasizes that any new genes utilized should not increase toxicity of the therapy in a clinical setting. Promising T-cell therapies with overexpressed, beneficial genes will also potentially be assessed in patients with relapsed/refractory B-cell malignancies. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.

Accelerating the identification of clinically relevant T cell therapies

admin_vjr_user — Thu, 31 Mar 2022 17:43:35 +0000

Elvira D’Ippolito, PhD, Technical University of Munich, Munich, Germany, describes her ongoing research into T cell responses to accelerate the identification of novel, clinically-relevant T cell therapies. She describes the development of functional screening methods based on T cell receptor (TCR) avidity to both identify TCR sequences that can recognize antigens of interest and predict TCR functionality. Dr D’Ippolito is also working on developing approaches to accelerate screening of TCRs to quickly identify lead candidates for clinical application, as well as the optimization of protocols for T cell engineering using non-viral CRISPR-cas9 technology. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.

Novel approaches in lymphocyte engineering

Simon Ng — Thu, 31 Mar 2022 14:40:57 +0000

Elvira D’Ippolito, PhD, Technical University of Munich, Munich, Germany, introduces a poster session that she is chairing at the International Conference on Lymphocyte Engineering (ICLE) 2022 on novel approaches in lymphocyte engineering. In this session, a novel avidity-controlled chimeric antigen receptor (AvidCAR) platform and a nanoparticle-sensitized photoporation approach for the safe engineering of therapeutic cells will be presented. In addition, Dr D’Ippolito describes a novel tumor model in humanized mice for the study of immunotherapy, as well as a study integrating CRISPR-cas9 screening and single-cell RNA sequencing to better understand transcriptional regulators and downstream gene networks in human regulatory T (Treg) cells. This interview took place at ICLE 2022.

Adapting cell therapies to solid tumors

Simon Ng — Thu, 24 Feb 2022 11:16:29 +0000

Nina Bauer, PhD, MBA, Merck KGaA, Darmstadt, Germany, outlines the key differences in manufacturing cell therapies for liquid and solid tumors and comments on some of the changes that need to be made to meet the future demand of cell therapies for solid tumors. Dr Bauer explains that cell therapies are still in their infancy and manufacturing therapies for both liquid and solid tumors require further optimization. Nevertheless, chimeric antigen receptor (CAR) T-cell therapy has been significantly more successful in liquid tumors due to easier tumor access and several changes need to be made for widespread adoption in solid tumors. Ongoing research is currently investigating which immune cells are the most efficient at penetrating solid tumors, as well as strategies to produce larger quantities of cells for a wider group of patients. This interview took place at Advanced Therapies Week 2022.

The advantages and applications of CRISPR-Cas 9

Simon Ng — Thu, 24 Feb 2022 11:16:26 +0000

Nina Bauer, PhD, MBA, Merck KGaA, Darmstadt, Germany, describes CRISPR-Cas 9 technology and its uses in advanced therapies. The enzymes utilized in CRISPR-Cas 9 is an efficient method of genome editing and is quicker and simpler than viral vectors. The technology can be applied in off-the-shelf therapies for solid tumors, where genome editing is necessary to reduce immunogenicity and to integrate the chimeric antigen receptor (CAR) onto the cell. This interview took place at Advanced Therapies Week 2022.