Gut microbiome and CAR-T therapy

Abid, Muhammad Bilal; Shah, Nirav N.; Maatman, Theresa; Hari, Parameswaran

doi:10.1186/s40164-019-0155-8

Cited by 39 publications

(28 citation statements)

References 59 publications

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“…Finally, it has been proposed that a further enhancement of CAR T-cell activity might be indirectly pursued through the manipulation of the gut microbiome, based on evidences supporting its critical role in the responses to other immune-based treatments, such as checkpoint inhibitors ( 144 ).…”

Section: Novel Car T Cell-based Approaches For B-cell Nhl and Cllmentioning

confidence: 99%

CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Clinical Trials and Real-World Experiences

Vitale

Strati

2020

Front. Oncol.

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Chimeric antigen receptor-modified (CAR) T cells targeting CD19 have revolutionized the treatment of relapsed or refractory aggressive B-cell lymphomas, and their use has increased the cure rate for these cancers from 10 to 40%. Two second-generation anti-CD19 CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved for use in patients, and the approval of a third product, lisocabtagene maraleucel, is expected in 2020. The commercial availability of the first two products has facilitated the development of real-world experience in treating relapsed or refractory aggressive B-cell lymphomas, shed light on anti-CD19 CAR T-cell products' feasibility in trial-ineligible patients, and raised the need for strategies to mitigate the adverse effects associated with anti-CD19 CAR T-cell therapy, such as cytokine release syndrome, neurotoxicity, and cytopenia. In addition, promising clinical data supporting the use of anti-CD19 CAR T-cell therapy in patients with indolent B-cell lymphomas or chronic lymphocytic leukemia have recently become available, breaking the paradigm that these conditions are not curable. Multiple clinical CAR T-cell therapy-based trials are ongoing. These include studies comparing CAR T-cell therapy to autologous stem cell transplantation or investigating their use at earlier stages of disease, novel combinations, and novel constructs. Here we provide a thorough review on the use of the anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma or with chronic lymphocytic leukemia, and present novel CAR T cell-based approaches currently under investigation in these disease settings.

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Section: Novel Car T Cell-based Approaches For B-cell Nhl and Cllmentioning

confidence: 99%

CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Clinical Trials and Real-World Experiences

Vitale

Strati

2020

Front. Oncol.

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“…Over the past decades, the conception that carcinoma represents a malignant disease type with both phenotypic and genetic heterogeneity has become completely accepted in the field of oncology. Although tremendous advancement has been achieved in precise management of this progressive disease [1][2][3], local invasion, distant metastasis and therapy resistance hinder survival improvement among tumor patients. A flurry of research has sprung up in order to throw light upon the underlying molecular mechanisms.…”

Section: Introductionmentioning

confidence: 99%

CD44 as a tumor biomarker and therapeutic target

et al. 2020

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CD44, a complex transmembrane glycoprotein, exists in multiple molecular forms, including the standard isoform CD44s and CD44 variant isoforms. CD44 participates in multiple physiological processes, and aberrant expression and dysregulation of CD44 contribute to tumor initiation and progression. CD44 represents a common biomarker of cancer stem cells, and promotes epithelial-mesenchymal transition. CD44 is involved in the regulation of diverse vital signaling pathways that modulate cancer proliferation, invasion, metastasis and therapy-resistance, and it is also modulated by a variety of molecules in cancer cells. In addition, CD44 can serve as an adverse prognostic marker among cancer population. The pleiotropic roles of CD44 in carcinoma potentially offering new molecular target for therapeutic intervention. Preclinical and clinical trials for evaluating the pharmacokinetics, efficacy and drug-related toxicity of CD44 monoclonal antibody have been carried out among tumors with CD44 expression. In this review, we focus on current data relevant to CD44, and outline CD44 structure, the regulation of CD44, functional properties of CD44 in carcinogenesis and cancer progression as well as the potential CD44-targeting therapy for cancer management.

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“…The gut microbiome is gaining unprecedented attention due to growing evidence of its role in immunotherapy. Bacteria belonging mainly to the Firmicutes and Verrucomicrobia phyla have specifically been shown to enhance responses to immunotherapy (10,11). Coincidently, bacteria belonging to the same phyla are associated with metabolism of dietary methionine in the human gut (12,13).…”

mentioning

confidence: 99%

“…Once methionine depletion strategy is validated in preclinical and clinical studies, combined gut microbiome manipulation and dietary modification hold promise for a cumulative impact on tumor growth inhibition and will carry broader therapeutic applications: from immuno-oncology to secluded solid tumor microenvironment (Figure 1). Adjunctive interventions such as single-or multi-strain probiotics (a rationally-designed consortia of live bacteria), prebiotics, narrow spectrum antibiotics, and fecal microbiota transplantation may further be examined (11,14).…”

mentioning

confidence: 99%