Anti-CD19 chimeric antigen receptor T-cell therapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia

Zhu, Yongjian; Zhao, Weihong; Tan, Youping; Du, Yuanyuan; Li, Zhi; Ou, Ruiming; Liu, Shuang; Pu, Chengfei; Jiang, Jing; Wang, Jinping; Xiao, Lanbo; Zhang, Qing

doi:10.1097/md.0000000000005676

Cited by 24 publications

(13 citation statements)

References 18 publications

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“…The tumor microenvironment plays an important role in the initiation and progression of a malignancy, including resistance to chemotherapy ( 137 , 138 ), as previously shown by our group. Lim and June have addressed this issue, linking CAR-T to targeting the malignant microenvironment as even if engineered T-cells may specifically recognize and target a cancer cell, the microenvironment has a suppressive effect on the CAR T-cells, thus limiting its efficacy ( 139 ).…”

Section: Genetic Engineered T-cells For the Immunotherapy Of Allmentioning

confidence: 55%

“…Good results are reported as a 90% complete remission rate in 30 patients with relapsed and refractory B-cell ALL ( 110 , 124 ). CAR-based therapy that involves the 4-1BB co-signaling domain can be of high clinical potential for relapsed Ph-positive ALL patients, as shown by Zhu et al ( 138 ). A negative aspect of this therapy refers to the side effects as described above: B-cell aplasia and CRS ( 124 , 139 ), as well as encephalopathy.…”

Section: Second-generation Car Constructs For Hematological Malignancmentioning

confidence: 96%

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Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

et al. 2018

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Chimeric antigen receptor (CAR) T-cell technology has seen a rapid development over the last decade mostly due to the potential that these cells may have in treating malignant diseases. It is a generally accepted principle that very few therapeutic compounds deliver a clinical response without treatment-related toxicity, and studies have shown that CAR T-cells are not an exception to this rule. While large multinational drug companies are currently investigating the potential role of CAR T-cells in hematological oncology, the potential of such cellular therapies are being recognized worldwide as they are expected to expand in the patient to support the establishment of the immune memory, provide a continuous surveillance to prevent and/or treat a relapse, and keep the targeted malignant cell subpopulation in check. In this article, we present the possible advantages of using CAR T-cells in treating acute lymphoblastic leukemia, presenting the technology and the current knowledge in their preclinical and early clinical trial use. Thus, this article first presents the main present-day knowledge on the standard of care for acute lymphoblastic leukemia. Afterward, current knowledge is presented about the use of CAR T-cells in cancer immunotherapy, describing their design, the molecular constructs, and the preclinical data on murine models to properly explain the background for their clinical use. Last, but certainly not least, this article presents the use of CAR T-cells for the immunotherapy of B-cell acute lymphoblastic leukemia, describing both their potential clinical advantages and the possible side effects.

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Section: Genetic Engineered T-cells For the Immunotherapy Of Allmentioning

confidence: 55%

Section: Second-generation Car Constructs For Hematological Malignancmentioning

confidence: 96%

Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

et al. 2018

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“…Chimeric antigen receptor (CAR) T‐cells have potentially changed the treatment of relapsed and refractory lymphoid malignancies and are currently approved for the treatment of young patients with B‐ALL who were resistant to more than two lines of therapies (Table ). Data regarding their efficacy in relapsed Ph+ ALL are scant and only two case reports of clinical efficacy have been published . Tisagenlecleucel, a CD 19 CAR T‐cell product, was recently approved by the FDA for treatment of patients with Ph+ ALL, 25 years of age or younger, who have refractory disease or have experienced two relapses with failure of two TKIs.…”

Section: Antibody‐based Therapy For Ph+ Allmentioning

confidence: 99%

Advances in BCR/ABL positive ALL

Horowitz

Rowe

2019

Adv Cell Gene Ther

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The advent of tyrosine kinase inhibitors (TKIs) has ushered in a new era in the management of patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ ALL). Although, as a group, these inhibitors have led to one of the most successful targeted therapies in leukemia, Ph+ ALL still remains a formidable disease. Unlike chronic myeloid leukemia (CML) where TKIs lead to dramatic long‐lasting responses as single agents, the biology of Ph+ ALL is far more complex and adjunctive therapies are mandatory. These may include corticosteroids, chemotherapy, antibody‐based therapies or, even, allogeneic hematopoietic cell transplantation. Clearly, other genes or mutations are in place that affect the outcome of Ph+ ALL. Additional chromosomal abnormalities are common in Ph+ ALL and have a varying impact on prognosis; some adverse, others less so. Genomic alterations have come into their own in the last decade and have increased our understanding of the mechanisms of resistance and differing responses to therapy. In this review, these genetic aberrations will be considered in some detail. In addition, innovations in current practice – including the use of immunological therapies – will be carefully reviewed. For the first time in decades, the long‐held imperative requiring an allogeneic transplant for a curative approach in adult Ph+ ALL is now being questioned and clinical trials are underway to resolve this issue. However, despite much progress in the past two decades, both in the biology and therapy of Ph+ ALL, this disease still presents a compelling challenge and much remains to be overcome.

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“… 7 , 8 Meanwhile, anti-CD19 CAR T-cell therapy has also been reported to provide partial remission on bone marrow relapse in Ph-positive ALL patients previously receiving HSCT therapy. 9 , 10 Here, we describe a Ph-positive ALL patient with extramedullary relapse after HSCT therapy, who received anti-CD19 CAR T-cells infusions.…”

Section: Introductionmentioning

confidence: 99%

Extramedullary relapse of acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation treated by CAR T-cell therapy: a case report

Wang

Shi

Wang³

et al. 2018

OTT

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Philadelphia chromosome-positive (Ph-positive) acute leukemia (ALL) accounts for around one quarter of adult cases of ALL and is usually associated with poor prognosis. The patients still encounter a high rate of relapse even after they receive hematopoietic stem cell transplantation (HSCT). HSCT is considered the established therapy and best option for many malignant ALL cases, however, disease relapse remains the main reason of failure. In recent years, chimeric antigen receptor (CAR) T-cell therapy has become a promising treatment for patients with advanced blood cancers. Here, we report a rare case of a Ph-positive ALL patient with extramedullary relapse in her cervix after receiving allogeneic HSCT. Given the unsatisfactory response to chemotherapy, tyrosine kinase inhibitor (TKI) treatment, and HSCT transplantation, she had received CD19+ CAR T-cell therapy 8 months earlier. The following ultrasound check indicated that her cervix relapse went through significant remission with almost undetectable tumor mass. This case strongly supports the efficacy of CAR T-cell therapy on adult ALL with extramedullary relapse.

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Anti-CD19 chimeric antigen receptor T-cell therapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia

Abstract: Supplemental Digital Content is available in the text

Cited by 24 publications

References 18 publications

Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

Advances in BCR/ABL positive ALL

Extramedullary relapse of acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation treated by CAR T-cell therapy: a case report

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