Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia

Leick, Mark B.; Silva, Harrison; Scarfò, Irene; Larson, Rebecca C.; Choi, Bryan D.; Bouffard, Amanda A.; Gallagher, Kathleen M.E.; Schmidts, Andrea; Bailey, Stefanie R.; Kann, Michael C.; Jan, Max; Wehrli, Marc; Grauwet, Korneel; Horick, Nora; Frigault, Matthew J.; Maus, Marcela V.

doi:10.1016/j.ccell.2022.04.001

Cited by 79 publications

(66 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To address the challenge of CAR T cells in AML, Leick and colleagues 1 targeted the CD70-CD27 axis, specifically because CD70 is both absent on normal hematopoietic cells and highly expressed on AML blasts, 3 and the experience with antibody-based approaches targeting CD70 has been promising. 4 They subsequently used an orthogonal approach to both rationally design CAR T cells with improved efficacy and incorporate pharmacodynamic regulation of leukemia antigen expression to synergize with CAR T cell function ( Figure 1 ).…”

Section: Main Textmentioning

confidence: 99%

“…Thus, utilizing truncated CD27 as the CAR antigen-binding domain, which may have improved functionality over alternate scFvs, 3 Leick and colleagues 1 incorporated a CD8α hinge to CD70-targeting CAR T cells. Additionally, because CD27 can be proteolytically cleaved from the cell membrane by matrix metalloproteases, 3 potentially limiting its efficacy, an in silico tool to approximate the location of the cleavage site to the CD27 hinge 8 was used to generate a panel of CARs with cleavage-resistant hinges.…”

Section: Main Textmentioning

confidence: 99%

“…Using these strategies, there was augmented avidity, resulting in improved CAR T cell expansion and enhanced efficacy, thereby sustaining durable in vivo responses in mice. 1 Furthermore, despite equal in vitro cytotoxic potential, in vivo treatment of AML-bearing mice with CD8α hinge-containing CAR T cells resulted in improved anti-leukemia efficacy and a significantly increased probability of survival.…”

Section: Main Textmentioning

confidence: 99%

“…Importantly, the work by Leick et al. 1 represents an important step forward in addressing the roadblocks faced by CAR T cell therapeutics for AML. The strategic design, together with the use of AZA to increase CD70 expression on leukemia, represents a synergistic approach toward testing a new therapeutic option in patients with r/r AML.…”

Section: Main Textmentioning

confidence: 99%

“… Using a multimodal approach toward developing a new CD70-targeted Chimeric antigen receptor (CAR) T cell in acute myeloid leukemia, Leick et al. 1 report on their synergetic strategy, which incorporates both CAR T cell construct modifications with enhancement of leukemia antigen expression to improve CAR T cell functionality. …”

mentioning

confidence: 99%

See 4 more Smart Citations

CD70 CAR T cells in AML: Form follows function

Mirazee

Shah

2022

Cell Reports Medicine

View full text Add to dashboard Cite

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

CD70 CAR T cells in AML: Form follows function

Mirazee

Shah

2022

Cell Reports Medicine

View full text Add to dashboard Cite

Four challenges to CAR T cells breaking the glass ceiling

et al. 2023

Self Cite

View full text Add to dashboard Cite

Cell‐based therapies using chimeric antigen receptor T cells (CAR T) have had dramatic efficacy in the clinic and can even mediate curative responses in patients with hematologic malignancies. As living drugs, engineered cells can still be detected in some patients even years after the original infusion. The excitement around the cell therapy field continues to expand as recent reports have shown that CAR T cells can induce remission in patients with autoimmune disease. While these promising advances in the field garner hope for wide‐spread utility of CAR T therapies across diseases, several roadblocks exist that currently limit the access and efficacy of this therapy in the clinic. Herein, we will discuss four major obstacles that the CAR T field faces, including toxicity, identifying tumor‐specific antigens, improving function in solid tumors, and reducing manufacturing complexity and cost. CAR T cells have potential for a multitude of diseases, but these glass ceilings will need to be broken in order to improve clinical responses and make this potentially life‐saving therapy accessible to a larger patient population.

show abstract

Biomimetic nanoparticles targeting atherosclerosis for diagnosis and therapy

Wang

Xie

2023

Smart Medicine

View full text Add to dashboard Cite

Atherosclerosis is a typical chronic inflammatory vascular disease that seriously endangers human health. At present, oral lipid‐lowering or anti‐inflammatory drugs are clinically used to inhibit the development of atherosclerosis. However, traditional oral drug treatments have problems such as low utilization, slow response, and serious side effects. Traditional nanodrug delivery systems are difficult to interactively recognize by normal biological organisms, and it is difficult to target the delivery of drugs to target lesions. Therefore, building a biomimetic nanodrug delivery system with targeted drug delivery based on the pathological characteristics of atherosclerosis is the key to achieving efficient and safe treatment of atherosclerosis. In this review, various nanodrug delivery systems that can target atherosclerosis are summarized and discussed. In addition, the future prospects and challenges of its clinical translation are also discussed.

show abstract

Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia

Cited by 79 publications

References 78 publications

CD70 CAR T cells in AML: Form follows function

CD70 CAR T cells in AML: Form follows function

Four challenges to CAR T cells breaking the glass ceiling

Biomimetic nanoparticles targeting atherosclerosis for diagnosis and therapy

Contact Info

Product

Resources

About