TCR Therapy – VJRegenMed

Multivalent gamma-delta T-cells: promising agents for the treatment of cancers

Anya Kerkache — Wed, 08 Mar 2023 10:35:19 +0000

In this video, Jürgen Kuball, MD, PhD, Utrecht University, Utrecht, The Netherlands, briefly discusses the promise of novel gamma delta T-cells, which are being explored for the treatment of various cancers and have shown promising pre-clinical results. 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.

An insight into novel third-generation TLR2 co-stimulatory CAR-T cells

Anya Kerkache — Wed, 08 Mar 2023 10:35:15 +0000

In this video, Yasmin Nouri, BSc, MSc, Malaghan Institute of Medical Research, Wellington, New Zealand, shares some insights into the development of a novel third-generation TLR2 co-stimulatory CAR-T cell product for the treatment of B-cell malignancies, which has demonstrated promising activity in a Phase I clinical 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.

Optimizing the upscaling and outscaling of CAR T-cell therapies

Simon Ng — Thu, 14 Apr 2022 15:56:43 +0000

Saskia Rösch, PhD, Miltenyi Biotec, Bergisch Gladbach, Germany, describes novel approaches to enhance chimeric antigen receptor (CAR) T-cell manufacturing. Upscaling can incur cost-related barriers, especially for T-cell receptor (TCR) and allogeneic therapies in solid tumor indications, and utilizing non-viral vectors as well as reducing the cultivation time may ameliorate the aforementioned issues. Developers additionally face issues in outscaling due to complications in material and documentation management, and Dr Rösch suggests decentralization as a potential solution. Regulatory authorities must also collaborate to expedite the development of T-cell therapies. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.

Moving CAR T-cell therapies to earlier lines of therapy in multiple myeloma

Simon Ng — Tue, 12 Apr 2022 11:18:07 +0000

Angela Krackhard, MD, PhD, Technical University of Munich, Munich, Germany, comments on the impact of ciltacabtagene autoleucel (cilta-cel) in the multiple myeloma treatment landscape. Cilta-cel is chimeric antigen receptor (CAR) T-cell therapy with two recognition epitopes that target B-cell maturation antigen (BCMA) and had displayed encouraging results for patients with relapsed/refractory multiple myeloma, especially in those who progress from proteosome inhibitors and anti-CD38 antibodies. It additionally is being assessed in earlier settings, especially due to the heterogeneity of the disease. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.

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.

Improving immune-imaging tools to assess cancer immunotherapies

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

Angela Krackhard, MD, PhD, Technical University of Munich, Munich, Germany, discusses challenges in utilizing non-invasive immune-imaging tools as predictive and surrogate markers. Whilst assessing minimal disease residue (MRD) in multiple myeloma is well established, imaging T-cell activity and subsequent tumor regression is limited for immunotherapies. Measuring CD8 activity without T-cell depletion is important and fragmented antibodies can examine the extent of T-cell infiltration in the tumor. Prof. Krackhard also describes using these imaging techniques to detect tumor flare reaction (TFR) and pseudoprogression, which can normally hamper response evaluation. 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.

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.