AbstractChimeric antigen receptor T‐cell (CAR‐T) therapy is a revolutionary approach in cancer treatment. More than 10 CAR‐T products have already approved on market worldly wide, and they use either gamma retroviral vectors or lentiviral vectors to deliver the CAR gene. Both vectors have the ability to effectively and persistently integrate the CAR gene into T cells. Despite the advancements in CAR‐T therapy, the potential risks associated with the vectors, particularly the risks of the secondary malignancies, still remain as a concern. This article compares the characteristics of gamma retroviral and lentiviral vectors, discusses the development of vector packaging systems, and examines the design of self‐inactivating (SIN) vectors. It also addresses the risks of secondary malignancies that might possibly be associated with the retroviral vectors, and the strategies to decrease the risks and increase the safer clinical use of the vectors. This article also discusses the current regulatory landscape and management approaches aiming to mitigate these risks through stringent safety measures and ongoing monitoring. Future perspectives focus on improving the safety profiles of the vectors and broadening their scope of use. The article provides a thorough overview of the most recent research discoveries and regulatory updates in the field of CAR‐T therapy, highlighting the significance of a balanced strategy that strikes a balance between innovation and patient safety in the development and implementation of CAR‐T therapy.

2025-01-01·British Journal of Haematology

Secondary haematological dysplasia after CAR‐T‐cell therapy for acute lymphoblastic leukaemia in children

Article

作者: Sanchez‐Sierra, Nazaret ; Alonso‐Saladrigues, Anna ; Isola, Ignacio ; Diaz de Heredia, Cristina ; Torrebadell, Montse ; Conde, Nuria ; Esperanza‐Cebollada, Elena ; Andreu, Sandra ; Sarrate, Edurne ; Rives, Susana ; Camós, Mireia ; Català, Albert ; Verdú‐Amorós, Jaime ; Dapena, Jose‐Luis ; López‐Duarte, Mónica ; Theron, Alexandre ; Cuatrecasas, Esther

SummaryThe use of CAR‐T is becoming more widespread in the treatment of haematological malignancies. In adults, secondary myelodysplastic syndromes (MDS) after CAR‐T have been described. However, there are currently no data on the risk of MDS following CAR‐T in children treated for acute lymphoblastic leukaemia (ALL). We studied all children treated with CAR‐T cells at Hospital Sant Joan de Déu in Barcelona and those with persistent cytopenias were evaluated at the cytological, cytogenetic, and molecular levels to look for MDS. A total of 106 patients received CAR‐T for ALL. Among 40 patients without early relapse or subsequent therapy after CAR‐T, four fulfilled the WHO criteria for myelodysplasia. These four patients had received a haematopoietic stem cell transplantation (HSCT) prior to CAR‐T and presented cytopenias with severe dysplastic changes in bone marrow after CAR‐T. One patient had clonal MDS with high‐risk cytogenetics arising from the host cells requiring a HSCT. Three patients had non‐progressive dysplasia arising from the donor cells. Two are alive in complete remission with stable cytopenias and one succumbed to ALL relapse. This is the first description of post‐CAR‐T MDS and haematological dysplasia in children and highlights the need to monitor children with persistent post‐CAR‐T cytopenias.

2025-01-01·Journal of Immunology Research

Advancements and Future Directions of Dual‐Target Chimeric Antigen Receptor T‐Cell Therapy in Preclinical and Clinical Studies

Review

作者: Liu, Haizhou ; Zhang, Chenyun

In recent years, chimeric antigen receptor T‐cell (CAR‐T) therapy has made groundbreaking progress in the treatment of various cancer types, particularly hematological malignancies. In the meantime, various preclinical and clinical studies have extensively explored dual‐target CAR‐T therapies which can be designed to recognize two antigens simultaneously based on the immunophenotype of tumor cells. Compared with single‐target CAR‐T approach, dual‐target CAR‐T therapies demonstrate varying degrees of superior antitumor CAR effects, prevent antigen escape and relapse, reduce on‐target off‐tumor effects, and ensure durable responses in different types of cancer. These advantages highlight the potential future prospects in this field, showing varying degrees of advancement in preclinical and clinical studies. Herein, we aimed to review different dual‐target CAR‐T studies conducted on a wide range of tumor models, summarizing the selection of target combinations, the efficacy and safety demonstrated in preclinical and clinical settings, the existing limitations, and the potential future directions of this promising therapeutic strategy.

项与 CAR-T(Yinkang Biopharma, Inc) 相关的新闻（医药）

2017-05-26

·BioSpace

How Much Juno Spent on Its Failed CAR-T Drug

May 26, 2017 By Alex Keown , BioSpace.com Breaking News Staff SEATTLE – Juno Therapeutics failed CAR-T therapy JCAR015, cost the company $46.4 million, according to analyst calculations. In March, Juno pulled the plug on JCAR015 , a once-promising CAR-T treatment. The decision to pull the plug on the therapy came only four months after a clinical trial evaluating of JCAR015 was halted for the second time following patient deaths. The trial was previously halted in the summer of 2016 following the deaths of three patients, but was cleared to resume by the U.S. Food and Drug Administration within days of the incident. All five patients suffered from cerebral edemas. The trial included adult patients with relapsed or refractory B cell acute lymphoblastic leukemia. So, after several years of research and trial data, not to mention the man hours spent in developing the CAR-T therapy and of course the lost lives, in The Motley Fool Brian Orelli calculated what the financial costs of the failed drug. Here’s Orelli’s breakdown over how much money Juno spent on that one therapy from 2013 until earlier this year: • Aug. 5, 2013 to Dec. 31, 2013 -- $7.7 million • 2014 -- $4.2 million • 2015 -- $11.3 million • 2016 -- $21.1 million • Q1 2017 -- $2.2 million Those figures add up to $46.4 million, but Orelli added the caveat that the numbers could increase depending on “wrap-up costs.” While JCAR015’s failure was certainly disappointing for Juno and its deep-pockets partner Celgene , the company does have a number of other potential therapies in its pipeline. The company’s top candidate is JCAR017, a CD19-directed CAR T cell product. JCAR017 received breakthrough therapy designation from the FDA for the treatment of patients with relapsing and remitting aggressive large B-cell non-Hodgkin’s Lymphoma, including DLBCL. Juno is expected to present data on JCAR017 and JCAR014, a CD19-targetting treatment for acute lymphoblastic leukemia, at the American Society of Clinical Oncology (ASCO) meeting in Chicago. Juno is expected to present Phase I data for JCAR017 in patients with NHL that have failed other treatments, as well as a Phase I safety presentation for JCAR014. The JCAR014 presentation will also include data on clinical and laboratory biomarkers that may allow early identification of cytokine release syndrome (CRS) and neurotoxicity (NT), the company said. The failure of JCAR015 allowed rival CAR-T drugmaker Kite Pharma to surge ahead with its non-Hodgkin lymphoma therapy, axicabtagene ciloleucel. However, that drug, which completed Phase III trials earlier, had its own setback earlier this month when Kite announced a patient taking the therapy died during the trial. Despite that setback, Kite still has hopes for bringing its CAR-T treatment to market this year. Chimeric Antigen Receptor T-Cell Therapies (CAR-T) are engineered in a laboratory to recognize a specific antigen in a cell and then administered into a cancer patient. The CAR-T cells should, if all goes as planned, multiply within the body and target the antigen and eliminate the threat. However, as Juno and Kite have shown, one safety issue associated with the treatment is the so-called cytokine storm, a condition in which a patient’s immune system becomes overstimulated and attacks the body.

细胞疗法临床3期临床1期ASCO会议免疫疗法

2017-03-02

·BioSpace

Juno Finally Drops Problem CAR-T Drug That Caused Deaths

March 2, 2017 By Alex Keown , BioSpace.com Breaking News Staff SEATTLE – Juno has pulled the plug on its once-promising lead CAR-T cancer treatment JCAR015. The announcement sent shares of Juno down nearly 8 percent in pre-market trading to $23.35. The decision to pull the plug on the therapy came only four months after a clinical trial evaluating of JCAR015 was halted for the second time following patient deaths. In November, the trial was halted after the report of two deaths. It had previously been halted in the summer of 2016 following the deaths of three patients, but was cleared to resume by the U.S. Food and Drug Administration within days of the incident. All five patients suffered from cerebral edemas. The trial included adult patients with relapsed or refractory B cell acute lymphoblastic leukemia. The July deaths sparked a class action lawsuit that alleges the company violated federal securities law. The lawsuit, filed in July alleges Hans Bishop , Juno’s chief executive officer, and the company, did not inform investors of a patient death in a Phase II trial of its lead drug. In its statement, Juno said it does believe there is a future for JCAR015, but that would require the establishment of preliminary safety and dose levels in a Phase I trial, which makes it unlikely.In a statement on Wednesday, Juno Chief Executive Officer Hans Bishop called the past year a “year of progress and learning for Juno and the cancer immunotherapy field.” “We remain committed to developing better treatments for patients battling ALL and believe an approach using our defined cell technology is the best platform to pursue. We intend to begin a trial with a defined cell product candidate in adult ALL next year. We look forward to sharing detailed data supporting our learnings from the ROCKET trial at an upcoming scientific conference,” Bishop said in a statement. As Juno shelves its JCAR015, the company will turn its attention to another experimental treatment, JCAR017, CD19-directed CAR T cell product candidates, for the treatment of diffuse large B cell lymphoma. The therapy has shown promise in early-stage trials, the company said, with 60 percent of patients showing a complete response to the treatment. However, the company is way behind rivals Kite Pharma and Novartis in the race to be the first to have an approved CAR-T therapy. Kite anticipates filing for regulatory approval following an announcement earlier this week that its lead CAR-T candidate axicabtagene ciloleucel (previously referred to as KTE-C19 ) for diffuse large B-cell lymphoma met its primary endpoints in a critical study. JCAR017 received breakthrough therapy designation from the FDA for the treatment of patients with relapsing and remitting aggressive large B-cell non-Hodgkin’s Lymphoma, including DLBCL. Bishop said the company remains optimistic about the future of JCAR017 and the other products in its pipeline. “We expect 2017 will be a data-rich year of key insights, based on up to 20 ongoing trials by year end, and we plan to present data from these trials as appropriate throughout the year,” Bishop said. Chimeric Antigen Receptor T-Cell Therapies (CAR-T) are engineered in a laboratory to recognize a specific antigen in a cell and then administered into a cancer patient. The CAR-T cells should, if all goes as planned, multiply within the body and target the antigen and eliminate the threat.

细胞疗法免疫疗法临床2期突破性疗法

100 项与 CAR-T(Yinkang Biopharma, Inc) 相关的药物交易

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