Acute Myeloid Leukemia – 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.

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.

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.

Challenges with CAR-T therapy in AML & insights into IF-BETTER-gated CAR-T cells

Anya Kerkache — Wed, 08 Mar 2023 10:35:16 +0000

Sascha Haubner, MD, Memorial Sloan Kettering Cancer Center, New York, NY, discusses challenges with developing efficacious CAR-T cell products for the treatment of patients with acute myeloid leukemia (AML), highlighting the heterogeneity of this disease. Dr Haubner then shares some insights into the development of IF-BETTER-gated CAR-T cells, which have demonstrated promising pre-clinical activity and will soon be evaluated in a first-in-human trial. 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.

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.

Results from a Phase I trial of rapidly manufactured Prgn-3006 Ultracar-T in R/R AML

Anya Kerkache — Thu, 26 Jan 2023 12:11:28 +0000

In this video, David Sallman, MD, Moffitt Cancer Center, Tampa, FL, outlines the completed Phase I results for Prgn-3006 Ultracar-T in patients with relapsed/refractory (R/R) CD33+ acute myeloid leukemia (AML). Prgn-3006 Ultracar-T is an autologous CAR-T cell product with decentralized manufacturing that significantly reduces the time between apheresis and CAR-T infusion compared to standard autologous CAR-T therapies. Overall, results suggest that Prgn-3006 Ultracar-T is well tolerated, with only a few grade 3 cytokine release syndrome (CRS) events and no dose-limiting toxicities. 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.

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.

Harnessing lipid-specific TCRs to target CD1c-expressing leukemia

Simon Ng — Wed, 06 Apr 2022 13:26:04 +0000

Michela Consonni, PhD, San Raffaele Scientific Institute, Millan, Italy, discusses strategies to utilize CD1c-restricted T lymphocytes to target CD1c+ leukemia cells, which express methyl-lysophosphatidic acids (mLPAs). Out of the five CD1c self-reactive T cell clones created, DN4.99 TCR-T cells were found to target CD1c-expressing leukemia the most efficiently without killing normal cells. Dr Consonni additionally discusses efforts to enhance the avidity of the T-cell product, as well as generating novel CD1c-expressing mouse models to further assess the safety and efficacy of these engineered T-cells. 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.