ESGCT 2021 – VJRegenMed

Challenges with translating gene therapies for neurodevelopmental disorders

admin_vjr_user — Fri, 31 Dec 2021 10:38:55 +0000

Ralf Schmid, PhD, MSCR, University of Pennsylvania, Philadelphia, PA, discusses the major challenges associated with the translation of gene therapies for neurodevelopmental disorders (NDDs) to the clinic. He explains the difficulty in translating therapies for NDDs from mouse models into non-human primate models and humans, given the increased brain size and complexity which support higher-level brain function. In addition, when attempting to use gene therapy approaches to restore lost gene expression seen in NDDs such as CDKL5-deficiency disorder (CDD), it can be difficult to model and predict which neurons need to be targeted in order to achieve lasting benefit in patients. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

Non-viral gene delivery & gene editing: highlights from ESGCT

admin_vjr_user — Fri, 31 Dec 2021 10:38:53 +0000

Ralf Schmid, PhD, MSCR, University of Pennsylvania, Philadelphia, PA, describes some of his highlights from the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021, which included important basic and translational research in cell and gene therapies. Dr Schmid discusses advances seen in non-viral delivery strategies for gene therapies following lessons learned from the development of the COVID-19 vaccine. He also explains that much progress has been made in gene editing during the pandemic including the development of new strategies for improving safety and efficacy of gene editing, which hold promise for the treatment of brain disorders in the future. This interview took place at the ESGCT Virtual Congress 2021.

CAR-Tregs for the treatment of systemic lupus erythematosus

admin_vjr_user — Fri, 31 Dec 2021 10:38:51 +0000

Chiara Bonini, MD, Vita-Salute San Raffaele University & IRCCS San Raffaele Institute, Milan, Italy, describes the rationale behind the delivery of regulatory T cells (Tregs) for the treatment of autoimmune diseases, given their ability to maintain self-tolerance and suppress the immune response. Dr Bonini also introduces ongoing research employing chimeric antigen receptor (CAR) technology to redirect Treg activity, with the aim of restoring immune tolerance in systemic lupus erythematosus (SLE). This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

RP-L301 lentiviral gene therapy for PKD

admin_vjr_user — Mon, 27 Dec 2021 12:22:59 +0000

Jose-Luis López-Lorenzo, MD, University Hospital Jimenez Diaz, Madrid, Spain, describes ongoing research into RP-L301, an investigational lentiviral gene therapy for pyruvate kinase deficiency (PKD). This approach involves autologous hematopoietic stem cells being transduced ex vivo with a lentiviral vector carrying a functional copy of the deficient PKLR gene. Based on preclinical studies in a murine model of PKD, a Phase I clinical trial (NCT04105166) evaluating RP-L301 is currently underway. While results obtained from two patients treated so far are promising, Dr López-Lorenzo notes that data from the treatment of more patients with a longer follow-up time is needed and highlights the need for a less complex and safer treatment protocol in the future. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

An update on the Phase I trial evaluating RP-L301 in PKD

admin_vjr_user — Mon, 27 Dec 2021 12:22:57 +0000

Jose-Luis López-Lorenzo, MD, University Hospital Jimenez Diaz, Madrid, Spain, provides an update on a Phase I clinical trial (NCT04105166) evaluating the safety of RP-L301, an investigational lentiviral gene therapy, in patients with pyruvate kinase deficiency (PKD). Dr López-Lorenzo outlines the study design, which involves the collection of peripheral blood hematopoietic stem cells (HSCs) which are transduced with a lentiviral vector carrying a functional copy of the deficient PKLR gene. Patients then receive a busulfan-containing conditioning regimen and then intravenous infusion of the RP-L301 HSC product. In the first two patients treated, hemoglobin levels were restored to normal levels, both report improved quality of life and no serious adverse events have been attributed to RP-L301. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

Gene therapy for PKD: addressing the unmet clinical need

admin_vjr_user — Mon, 27 Dec 2021 11:13:30 +0000

Jose-Luis López-Lorenzo, MD, University Hospital Jimenez Diaz, Madrid, Spain, describes the therapeutic landscape for pyruvate kinase deficiency (PKD), a rare inherited hemolytic anemia caused by mutations in the PKLR gene. Treatment of PKD is currently largely limited to blood transfusion, chelation therapy and splenectomy, which are associated with significant side effects. Dr López-Lorenzo discusses the rationale behind the development of gene therapies for PKD, such as the transplantation of autologous hematopoietic stem cells containing a functional copy of the deficient PKLR gene. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

Highlights from ESGCT 2021: gene therapy clinical data, advances in gene editing & AAV toxicity

admin_vjr_user — Fri, 24 Dec 2021 10:13:24 +0000

Paul Wuh-Liang Hwu, MD, PhD, National Taiwan University Hospital, Taipei, Taiwan, offers some of his highlights from the 2021 European Society of Gene & Cell Therapy (ESGCT) Congress. He discusses his excitement around promising clinical data presented at the meeting evaluating various gene therapy approaches in rare disorders such as mucolipidosis III, as well as advances in gene editing and the promise of base editing. He also considers the importance of talks on the safety issues associated with gene therapy, such as the integration of adeno-associated virus (AAV) vectors into the liver, resulting in toxicity. This interview took place at the ESGCT Virtual Congress 2021.

Eladocagene exuparvovec: AAV2-mediated gene therapy for AADC deficiency

admin_vjr_user — Fri, 24 Dec 2021 10:07:54 +0000

Paul Wuh-Liang Hwu, MD, PhD, National Taiwan University Hospital, Taipei, Taiwan, describes the rationale and ongoing research into gene therapy for aromatic l-amino acid decarboxylase (AADC) deficiency. AADC deficiency is a very rare genetic disorder caused by mutations in the dopa decarboxylase gene leading to reduced AADC enzyme activity, resulting in delayed cognitive and speech development. Dr Hwu describes the study of eladocagene exuparvovec, a recombinant adeno-associated viral vector (AAV) serotype 2 carrying cDNA encoding the human AADC gene, which is administered via bilateral infusion to the putamen. Results demonstrate the efficacy of this treatment in improving cognition and motor development. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

Genome editing to address challenges with adoptive T-cell therapy

admin_vjr_user — Thu, 23 Dec 2021 16:24:58 +0000

Chiara Bonini, MD, Vita-Salute San Raffaele University & IRCCS San Raffaele Institute, Milan, Italy, describes the major hurdles associated with adoptive T-cell therapy for cancer, including challenges around determining appropriate molecular targets and type of T-cell product to use, as well as overcoming the tumor microenvironment. Dr Bonini highlights that genome editing can be used to address such challenges through the introduction or disruption of genes in the T-cell receptor (TCR) to impact specificity. In addition, tools such as CRISPR genome editing allow multiplexed strategies in which multiple genome modifications can be made in a single T-cell product, allowing modification of TCR specificity and sensitivity to the suppressive tumor microenvironment. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

TCR gene editing in cancer therapy

admin_vjr_user — Thu, 23 Dec 2021 16:24:56 +0000

Chiara Bonini, MD, Vita-Salute San Raffaele University & IRCCS San Raffaele Institute, Milan, Italy, describes the rationale behind the use of T-cell receptor (TCR) gene editing to improve adoptive T cell therapy for cancer. While chimeric antigen receptors (CAR) T-cell therapy can be a useful approach when targeting antigens present on the cancer cell surface, TCR therapy is often employed when targeting intracellular tumor antigens. Dr Bonini explains how TCR gene editing can allow better control of the level of expression, efficacy and safety profile of TCR therapy. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.