Disease Biology – VJRegenMed

Preliminary results from Phase I study of CD123 CAR-T therapy in pediatric R/R AML

Anya Kerkache — Thu, 09 Mar 2023 11:31:44 +0000

In this video, Swati Naik, MBBS, St. Jude Children’s Research Hospital, Memphis, TN, discusses the rationale and preliminary results from a Phase I study evaluating the safety and feasibility of CD123-targeting CAR-Ts in pediatric patients with relapsed/refractory (R/R) acute myeloid leukemia (AML; NCT04318678). Dr Naik first explains the challenges associated with designing effective CAR-Ts for AML, including the identification of a suitable target, patient heterogeneity, and the aggressive and immunosuppressive nature of the disease. Dr Naik then comments on the results of the study, which showed evidence of expansion and anti-leukemic activity at different dose levels, with no dose-limiting toxicities. This interview took place at the 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR® held in Orlando, FL.

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Treating otoferlin deficiency with gene therapy

Simon Ng — Thu, 23 Jun 2022 09:28:24 +0000

Nawal Ouzren, Sensorion, Montpellier, France, gives an overview of the rationale behind developing a gene therapy for patients with hearing loss who have an otoferlin deficiency. Otoferlin is a protein expressed in inner hair cells, which is sensitive to a certain frequency. Initial in vivo studies have successfully restored expression of otoferlin in animal models, who have regained functional hearing as a result of the gene therapy. This interview was conducted during Meeting on the Mediterranean 2022.

Novel gene therapy solutions for Usher syndrome type I

Simon Ng — Thu, 23 Jun 2022 09:28:23 +0000

Usher syndrome type I is a rare, congenital disease characterized by issues in the vestibular system, resulting in deafness, balance issues and blindness. Nawal Ouzren, Sensorion, Montpellier, France, discusses research efforts in treating Usher syndrome type I with gene therapy. Whilst vestibular function has been successfully restored in animal models, further research is required to restore hearing. This interview was conducted during Meeting on the Mediterranean 2022.

Developing gene therapies for GJB2 gene related hearing loss

Simon Ng — Thu, 23 Jun 2022 09:28:22 +0000

Nawal Ouzren, Sensorion, Montpellier, France, describes ongoing research into developing gene therapies for patients with hearing loss due to mutations in the GJB2 gene. This form of hearing loss is the most common form of childhood deafness, and some forms of adult hearing loss can be attributed to certain mutations of the GJB2 gene. Current efforts include elucidating a suitable therapeutic candidate in animal models. This interview was conducted during Meeting on the Mediterranean 2022.

Applications of stem cell gene therapy beyond genetic diseases

admin_vjr_user — Fri, 22 Apr 2022 12:21:18 +0000

Luigi Naldini, MD, PhD, San Raffaele Telethon Institute for Gene Therapy, Milano, Italy, comments on the potential application of stem cell gene therapy in oncology. In recent years, growing evidence supporting the efficacy and tolerability of this technology in genetic diseases has suggested it as a promising strategy to target tumors by engineering stem cells to target the tumor or to deliver a therapeutic agent. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT and CIBMTR® 2022 in Salt Lake City, Utah.

Developing individualized cancer therapies with neoantigen-specific TCRs

Simon Ng — Fri, 08 Apr 2022 12:51:14 +0000

Angela Krackhard, MD, PhD, Technical University of Munich, Munich, Germany, provides an overview of targeting neoantigens specifically expressed on tumors with T-cell receptors (TCRs). Proteogenomic analysis consisting of deep sequencing analysis and mass spectrometry detected novel neoantigens and were validated with patient-derived T-cells. Further analysis revealed certain T-cell receptors that can be restimulated in a shorter amount of time as a result of a lower activation threshold. Prof. Krackhard also describes the differential transcription profile of these T-cells and other highly activated T-cells, as well as their therapeutic potential. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.

Overcoming barriers in treating liquid tumors with T-cell therapies

Simon Ng — Thu, 07 Apr 2022 13:19:56 +0000

Michela Consonni, PhD, San Raffaele Scientific Institute, Millan, Italy, comments on what needs to be addressed to optimize chimeric antigen receptor (CAR) T-cell and T-cell receptor (TCR) therapies for leukemias and lymphomas. Further research is required to discover novel antigen targets solely expressed on tumors to avoid off-target side effects and to prevent antigen escape. Additional TCRs are also necessary for TCR-T cells to be compatible with a wider range of human leukocyte antigens (HLAs). Dr Consonni additionally highlights the risk of graft versus host disease (GvHD) in patients receiving hematopoietic stem cell transplantation (HSCT). This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.

The anti-leukemic potential of CD1c-restricted T cells

Simon Ng — Wed, 06 Apr 2022 13:26:05 +0000

Michela Consonni, PhD, San Raffaele Scientific Institute, Millan, Italy, gives an overview of newly identified methyl-lysophosphatidic acids (mLPAs) that are highly expressed in leukemia cells and are presented by CD1c, a monomorphic major histocompatibility complex (MHC) class I-like molecule. CD1c-restricted T lymphocytes have found to target CD1c+ leukemia cells and Dr Consonni highlights the advantages of these lipid-specific T cells as an alternative to existing T-cell therapies, including the lower risk of graft versus host disease (GvHD) as a result of CD1c being solely expressed in hematopoietic cells. This interview took place at the International Conference on Lymphocyte Engineering (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.

DSG3-CAART: A novel CAAR T-cell therapy in pemphigus vulgaris

Simon Ng — Thu, 27 Jan 2022 18:00:59 +0000

Samik Basu, MD, Cabaletta Bio, Philadelphia, PA, talks on the differences between chimeric autoantibody receptor (CAAR) T-cells and chimeric antigen receptor (CAR) T-cells. Unlike CD19-targeted CAR T-cells which target and kill all CD19-positive B-cells, CAAR T-cells selectively eliminate memory B-cells that give rise to plasma cells generating autoantibodies. Whilst the intracellular portion of CAAR T-cells and CAR T-cells are similar, the extracellular portion of the CAAR T-cell contains a portion of the protein targeted by the autoantibody. Dr Basu additionally outlines the design and early results of the Phase I, dose-escalation DesCAARTes trial (NCT04422912) investigating the maximum tolerated dose of DSG3-CAART, an autologous desmoglein 3 (DSG3) CAAR T-cell, in patients with mucosal-dominant pemphigus vulgaris (mPV). DSG3-CAART appears safe and a dose-dependent increase in CAAR T-cell persistence was observed within the first 29 days after infusion. This interview took place at Advanced Therapies Week 2022.