2021
DOI: 10.1182/blood-2021-146246
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Preservation of T-Cell Stemness with a Novel Expansionless CAR-T Manufacturing Process, Which Reduces Manufacturing Time to Less Than Two Days, Drives Enhanced CAR-T Cell Efficacy

Abstract: Background: Extended T-cell culture periods in vitro deplete the CAR-T final product of naive and stem cell memory T-cell (T scm) subpopulations that are associated with improved antitumor efficacy. YTB323 is an autologous CD19-directed CAR-T cell therapy with dramatically simplified manufacturing, which eliminates complexities such as long culture periods. This improved T-Charge™ process preserves T-cell stemness, an important characteristic closely tied to therapeutic potential, which leads to enhanced expan… Show more

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Cited by 23 publications
(17 citation statements)
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“…The authors showed that short-manufactured CAR T cells exhibited more robust tumor control compared to long-manufactured ones in a mouse xenograft model. Other groups have observed comparable results in similar xenograft mouse models ( 78 , 79 ) as well as clinical trials ( 78 , 80 ). In reality, due to prior lymphodepleting cancer treatment, the short-term ex vivo expansion protocol may not be feasible for patients with reduced T cell counts and activity.…”
Section: Impact Of Culture Periodsupporting
confidence: 53%
“…The authors showed that short-manufactured CAR T cells exhibited more robust tumor control compared to long-manufactured ones in a mouse xenograft model. Other groups have observed comparable results in similar xenograft mouse models ( 78 , 79 ) as well as clinical trials ( 78 , 80 ). In reality, due to prior lymphodepleting cancer treatment, the short-term ex vivo expansion protocol may not be feasible for patients with reduced T cell counts and activity.…”
Section: Impact Of Culture Periodsupporting
confidence: 53%
“…While early in development, it has shown promising responses (CR 83%) and durability (median DOR 16 months, 12‐month PFS of 50%) in the third‐line setting. It also appears to improve CART expansion and persistence with administration of lower doses of CART without translating into more apparent toxicity 105,106 …”
Section: Management Of Relapsed/refractory Diseasementioning
confidence: 99%
“…While early in development, it has shown promising responses (CR 83%) and durability (median DOR 16 months, 12-month PFS of 50%) in the third-line setting. It also appears to improve CART expansion and persistence with administration of lower doses of CART without translating into more apparent toxicity 105,106. ALLO-501 and ALLO-501A are examples of "off the shelf" allogeneic CARTs obtained from the peripheral blood of healthy donors.Both products have been modified to minimize the risk of graft versus host disease (GVHD).…”
mentioning
confidence: 99%
“…An important challenge of off-the-shelf CAR-T therapies manufactured from blood-derived mature T cells is the need to generate large batches of cells via extensive ex vivo expansion, which may limit their proliferative capacity and functionality in patients. New manufacturing techniques have been deployed to address this potential issue and allow CAR-T or CAR-NKT cells to maximize their capacity for expansion and persistent tumor cell killing in vivo [ 155 , 164 ]. To this end, the use of umbilical cord blood-derived CD34 + hematopoietic stem cells transduced with a non-alloreactive iNKT TCR as starting material presents several unique advantages [ 155 ].…”
Section: Future Perspectivesmentioning
confidence: 99%