Off the shelf T cell therapies for hematologic malignancies

McCreedy, Bruce; Senyukov, Vladimir; Nguyen, Kim

doi:10.1016/j.beha.2018.03.001

Cited by 25 publications

(28 citation statements)

References 37 publications

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“…Knock down of β2-microglobulin reduces the ability of class I HLA molecules to form heterodimers on the cell surface. Reducing expression of both β2-microglobulin and TRAC resulted in decreased allogeneic attack by CD8 T cells and NK cells [112]. This strategy may be useful to reduce allo-recognition in patients receiving CAR T cell therapy.…”

Section: Cd1amentioning

confidence: 95%

Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions

2019

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Chimeric antigen receptor (CAR) T cell therapy has been successful in treating B cell malignancies in clinical trials; however, fewer studies have evaluated CAR T cell therapy for the treatment of T cell malignancies. There are many challenges in translating this therapy for T cell disease, including fratricide, T cell aplasia, and product contamination. To the best of our knowledge, no tumor-specific antigen has been identified with universal expression on cancerous T cells, hindering CAR T cell therapy for these malignancies. Numerous approaches have been assessed to address each of these challenges, such as (i) disrupting target antigen expression on CARmodified T cells, (ii) targeting antigens with limited expression on T cells, and (iii) using third party donor cells that are either non-alloreactive or have been genome edited at the T cell receptor α constant (TRAC) locus. In this review, we discuss CAR approaches that have been explored both in preclinical and clinical studies targeting T cell antigens, as well as examine other potential strategies that can be used to successfully translate this therapy for T cell disease.

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Section: Cd1amentioning

confidence: 95%

Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions

2019

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“…Universal CAR-T cells derived from healthy donors, knocked out endogenous TCR gene and exhaustion genes which could prevent the generation of GVHD in MHC-mismatched recipients and functioning in long-term would be an ideal CAT-T cell product which is the so called off the shelf CAR-T cells. 62 , 63 , 64 A great challenge is disease relapse after CAR-T cell therapy, the production of the ‘off shelf therapy T cells’ which targeted different leukemia antigens may meet the salvage therapy needs of T cells when detection of leukemia relapse with a changed leukemia cell clone. An advantage of TCR-T cells is that they are capable of recognizing intracellular antigens and covering the shortage of CAR-T cells that can only recognize surface antigens.…”

Section: Redirected T Cellsmentioning

confidence: 99%

Approaches for generation of anti-leukemia specific T cells

Jin

2018

Cell Regeneration

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As three decades ago, it was reported that adoptive T cell immunotherapy by infusion of autologous tumor infiltrating lymphocytes (TILs) mediated objective cancer regression in patients with metastatic melanoma. A new era of T cell immunotherapy arose since the improvement and clinical use of anti-CD19 chimeric antigen receptor T cells (CAR-T) for the treatment of refractory and relapsed B lymphocyte leukemia. However, several challenges and difficulties remain on the way to reach generic and effective T cell immunotherapy, including lacking a generic method for generating anti-leukemia-specific T cells from every patient. Here, we summarize the current methods of generating anti-leukemia-specific T cells, and the promising approaches in the future.

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“…The adoptive transfer of T cells engineered to express artificial chimeric antigen receptors (CARs) that target a tumor cell surface molecule has emerged as an exciting new approach for cancer immunotherapy, with successful reports first published in 2011, showing the remarkable efficacy of CAR-T cells in treating hematological malignancies [1]. Clinical trials in patients with advanced B-cell malignancies treated with CD19-specific CAR-T cells have shown impressive antitumor efficacy [2].…”

Section: Introductionmentioning

confidence: 98%