Lentiviral Vectors – VJRegenMed

Safety and efficacy of LV20.19 CAR-T therapy in Richter’s transformation and R/R MCL

Anya Kerkache — Thu, 09 Mar 2023 11:31:47 +0000

Nirav Shah, MD, Medical College of Wisconsin, Milwaukee, WI, comments on the results of two studies evaluating the LV20.19 CAR-T product in patients with Richter’s transformation and in patients with heavily pretreated mantle cell lymphoma (MCL; NCT04186520). Out of the six patients with Richter’s transformation who were evaluated, four achieved a durable remission and the overall response rate (ORR) was 100%. Patients presented a unique toxicity profile, with a high incidence of hemophagocytic lymphohistiocytosis (HLH)-like toxicity. In MCL, eight of the 14 patients in the study met the primary endpoint, and the ORR at day 90 was 100%. This interview took place at the 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR® held in Orlando, FL.

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Enhancing the long-term functionality of CAR-T cells in solid tumors

Simon Ng — Mon, 11 Apr 2022 09:52:51 +0000

The efficacy of chimeric antigen receptor (CAR) T-cell therapy in solid tumors have been substandard as a result of CAR T-cell differentiation and exhaustion. Shigeki Yagyu, MD, PhD, Kyoto Prefectural University of Medicine, Kyoto, Japan, comments on the need to improve CAR T-cell potency in solid tumors by optimizing long-term functionality. Despite lentiviral vectors predominantly being used in the engineering of CAR T-cell therapies, they may affect T-cell activity during cell expansion. Dr Yagyu discusses strategies to boost CAR T-cell efficacy including lowering PD-1 expression and reducing T-cell exhaustion. This interview took place at the International Conference on Lymphocyte Engineering (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.”

OTL-103: An autologous gene therapy for Wiskott Aldrich syndrome

Simon Ng — Thu, 03 Mar 2022 17:46:27 +0000

Kent Christopherson, PhD, Orchard Therapeutics, Boston, MA, provides an overview of OTL-103, an investigational autologous gene therapy utilizing a lentiviral gene construct for patients with Wiskott Aldrich syndrome (WAS). OTL-103 aims to insert the corrected version of the WAS gene in patients, who often result in non-functioning leucocytes and platelets. Administration of the functioning cells will result in the cells differentiating into immune cells as well as the progenitor cells to platelets and a clinical trial is currently underway to assess the efficacy of OTL-103. This interview took place at Advanced Therapies Week 2022.

Novel gene therapies for metachromatic leukodystrophy

Simon Ng — Thu, 03 Mar 2022 17:46:25 +0000

Kent Christopherson, PhD, Orchard Therapeutics, Boston, MA, describes the development and mechanism of action of atidarsagene autotemcel, a gene therapy consisting of an autologous CD34⁺ cell enriched population that contains hematopoietic stem and progenitor cells (HSPC) transduced using a lentiviral vector. The gene therapy, which has been approved in the EU, aims to treat metachromatic leukodystrophy (MLD) and the vector encodes the human arylsulfatase-A (ARSA) gene, which is faulty in patients with MLD. HSPC cells with the functional gene can subsequently produce the correct protein, which can be trafficked and permanently integrated in the central nervous system (CNS). This interview took place at Advanced Therapies Week 2022.

Tangential Flow Depth Filtration in viral vector manufacturing

Simon Ng — Thu, 03 Mar 2022 17:46:23 +0000

Rachel Legmann, PhD, Repligen, Waltham, MA, discusses the Tangential Flow Depth Filtration (TFDF) platform and its benefits. TFDF combines tangential flow and depth filtration in a single closed system, enabling high cell density cultures for the production of various viral vectors such as adeno-associated viruses (AAV) and lentiviruses in gene therapies. A high cell density results in higher viral vector yields and a perfusion system allows the final product to be continuously collected. The platform additionally requires a lower surface area for defiltration, meaning that viral vectors can be manufactured in a shorter timeframe. This interview took place at Advanced Therapies Week 2022.

Challenges in manufacturing viral vectors for the clinic

Simon Ng — Mon, 28 Feb 2022 17:56:23 +0000

Nathalie Clement, PhD, Unicorn Consultations, Gainesville, FL, describes challenges in the development and production of clinically effective viral vectors. Manufacturing larger doses on a bigger scale has been a barrier for companies, and difficulties in purification has led to issues in potency and safety. Finding a standard method for purifying viral vectors is especially difficult when there are numerous varieties of viral vectors including adeno-associated viruses and lentiviruses. Whilst the demand for viral vector gene therapies have increased in certain disease areas such as Duchenne muscular dystrophy, safety concerns possibly relating to impurities in the product must be addressed. This interview took place at Advanced Therapies Week 2022.

Meeting the increasing demand for viral vectors

Simon Ng — Fri, 18 Feb 2022 15:46:07 +0000

Rachel Legmann, PhD, Repligen, Waltham, MA, describes issues in producing viral vectors and approaches to improve manufacturing capabilities. Low yield and constraints in bioreactor capacity affects a wide range of viral vectors including adeno-associated viral (AAV) vectors, lentiviral vectors, and oncolytic vectors. Additional barriers include the process of replicating viral vectors, where transfection and lysis are stages in the manufacturing process that are difficult to scale up. Viral vectors are also more difficult to produce cost effectively due to the stricter safety regulations needed. This interview took place at Advanced Therapies Week 2022.

Increasing patient recruitment to rare disease trials

Simon Ng — Mon, 14 Feb 2022 17:40:21 +0000

Will Chou, MD, Aruvant, New York, NY, provides his insights on approaches to solve recruitment issues in clinical trials for rare diseases such as sickle cell disease (SCD). He emphasizes the need to gain the trust of patients, who may not necessarily be knowledgeable of every aspect of the therapy, as well as being transparent with everyone involved in the trials. This interview took place at Advanced Therapies Week 2022.

MOMENTUM: ARU-1801 in sickle cell disease

Simon Ng — Mon, 07 Feb 2022 17:06:07 +0000

Will Chou, MD, Aruvant, New York, NY, presents preliminary results from the Phase I/II MOMENTUM study (NCT02186418) of ARU-1801, a lentiviral gene therapy, in patients with sickle cell disease (SCD). 5 patients are currently enrolled and the investigational therapy has a promising efficacy and safety profile, with no vaso-occlusive episodes (VOE) or hospital stays reported in patients. Dr Chou additionally reports a durable response in patients, with therapeutic hemoglobin detected in patients 3 years after initial administration. This interview took place at Advanced Therapies Week 2022.