Dataset Information

Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells.

ABSTRACT: While treatment for B-cell malignancies has been revolutionized through the advent of CAR immunotherapy, similar strategies for T-cell malignancies have been limited. Additionally, T-cell leukemias and lymphomas can commonly metastasize to the CNS, where outcomes are poor and treatment options are associated with severe side effects. Consequently, the development of safer and more effective alternatives for targeting malignant T cells that have invaded the CNS remains clinically important. CD5 CAR has previously been shown to effectively target various T-cell cancers in preclinical studies. As IL-15 strengthens the anti-tumor response, we have modified CD5 CAR to secrete an IL-15/IL-15sushi complex. In a Phase I clinical trial, these CD5-IL15/IL15sushi CAR T cells were tested for safety and efficacy in a patient with refractory T-LBL with CNS infiltration. CD5-IL15/IL15sushi CAR T cells were able to rapidly ablate the CNS lymphoblasts within a few weeks, resulting in the remission of the patient's lymphoma. Despite the presence of CD5 on normal T cells, the patient only experienced a brief, transient T-cell aplasia. These results suggest that CD5-IL15/IL15sushi CAR T cells may be a safe and useful treatment of T-cell malignancies and may be particularly beneficial for patients with CNS involvement.Graphical Abstract.

SUBMITTER: Feng J

PROVIDER: S-EPMC8036178 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells.

Feng Jia J Xu Haichan H Cinquina Andrew A Wu Zehua Z Chen Qi Q Zhang Ping P Wang Xingen X Shan Huiming H Xu Lei L Zhang Qian Q Sun Lihua L Zhang Wenli W Pinz Kevin G KG Wada Masayuki M Jiang Xun X Hanes William M WM Ma Yupo Y Zhang Hongyu H

Stem cell reviews and reports 20210106 2

While treatment for B-cell malignancies has been revolutionized through the advent of CAR immunotherapy, similar strategies for T-cell malignancies have been limited. Additionally, T-cell leukemias and lymphomas can commonly metastasize to the CNS, where outcomes are poor and treatment options are associated with severe side effects. Consequently, the development of safer and more effective alternatives for targeting malignant T cells that have invaded the CNS remains clinically important. CD5 C ...[more]

PMID: 33410096

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Project description:BackgroundAnaplastic Large Cell Lymphoma (ALCL) is one of the most common subtypes of T-cell lymphoma. Among these, refractory and relapsed (r/r) ALK positive ALCL lacks effective therapies. The chimeric antigen receptor-modified T (CAR-T) cell therapy holds great promise as a therapeutic strategy for this disease. However, it is not known yet whether anti-CD5 CAR-T cells are sufficient for the definitive treatment of relapsed ALK+ ALCL, nor the role of accurate laboratory-based diagnoses during CAR-T treatment.Case presentationThe adolescent patient received autologous T cells containing sequences encoding VH domains specific to CD5. Following the infusion, there was an increase in both the copy number and proportion of CAR-T cells in peripheral blood. IL-6 and ferritin levels in the patient exhibited significant fluctuations, with increases of 13 and 70 folds respectively, compared to baseline after the treatment. Additionally, adverse effects were observed, including grade 4 rash, grade 1 headache, nausea, and neck-pain. Surprisingly, a relapsed disease phenotype was identified based on the results of PET/CT and histopathological analysis of the inguinal lymph node biopsy. After conducting a thorough diagnostic assessment, which included flow cytometry, next-generation sequencing (NGS), examination of immune-related gene rearrangements, and analysis of the immune repertoire of T-cell receptors (TCR), we conclusively determined that the hyperplastic T cells identified in the lymph node were the result of an expansion of CAR-T cells. Ultimately, the patient has attained complete remission (CR) and has sustained a disease-free survival state for 815 days as of the cutoff date on August 30, 2023.ConclusionTaken together, the results demonstrate that anti-CD5 CAR-T cells can induce a clinical response in r/r ALK+ ALCL patient. Furthermore, this case underscores the importance of utilizing advanced technologies with high sensitivity and accuracy for biological detection in clinical laboratory diagnosis and prognosis in CAR-T cell treatment.Trial registration numberNCT04767308.

Dataset Information

Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells.

Publications

Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells.

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