Histone deacetylases inhibitor chidamide synergizes with humanized PD1 antibody to enhance T-cell chemokine expression and augment Ifn-γ response in NK-T cell lymphoma

Wen, Tingyu; Sun, Guang-Yi; Jiang, Wenxin; He, Xiaohong; Shi, Yuankai; Ma, Fei; Liu, Peng

doi:10.1016/j.ebiom.2022.104420

Cited by 8 publications

(4 citation statements)

References 43 publications

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“…Also, several clinical trials of HDAC inhibitors are being conducted, e.g., NCT01997840 (active status), NCT04231448, and NCT04674683 (recruiting status). As for LMW combination with conventional therapy, the striking example is the use of Chidamide [ 15 ], which is being studied in seven clinical trials in the III and IV phases. The next example is the use of O 6 -benzylguanine, an O 6 -alkylguanine-DNA alkyltransferase (AGT) inhibitor, in combination with standard therapy, which slows down the progression of glioblastoma and gliosarcoma in comparison with temozolomide treatment [ 16 ].…”

Section: Pharmacotherapeutic Approach For Epigenome Modulationmentioning

confidence: 99%

Current Approaches to Epigenetic Therapy

Griazeva,

Fedoseeva,

Radion

et al. 2023

Epigenomes

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Epigenetic therapy is a promising tool for the treatment of a wide range of diseases. Several fundamental epigenetic approaches have been proposed. Firstly, the use of small molecules as epigenetic effectors, as the most developed pharmacological method, has contributed to the introduction of a number of drugs into clinical practice. Secondly, various innovative epigenetic approaches based on dCas9 and the use of small non-coding RNAs as therapeutic agents are also under extensive research. In this review, we present the current state of research in the field of epigenetic therapy, considering the prospects for its application and possible limitations.

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Section: Pharmacotherapeutic Approach For Epigenome Modulationmentioning

confidence: 99%

Current Approaches to Epigenetic Therapy

Griazeva,

Fedoseeva,

Radion

et al. 2023

Epigenomes

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“… 19 , 20 HDACi also exhibit favorable immunomodulatory effects that improve anti-tumor immune responses generated in the setting of PD-1 blockade in various preclinical tumor models. 21–24 HDACi, for example, enhance tumor antigen presentation, increase recruitment of T cells into the tumor environment, and promote the function of tumor-reactive T cells, which results in significantly improved responses to PD-1 blockade therapy in preclinical models. 21–24 HDACi also increase PD-L1 expression on malignant cells from various tumor types, which may be an important determinant associated with PD-1 response in lymphoma and other malignancies.…”

Section: Introductionmentioning

confidence: 99%

“… 21–24 HDACi, for example, enhance tumor antigen presentation, increase recruitment of T cells into the tumor environment, and promote the function of tumor-reactive T cells, which results in significantly improved responses to PD-1 blockade therapy in preclinical models. 21–24 HDACi also increase PD-L1 expression on malignant cells from various tumor types, which may be an important determinant associated with PD-1 response in lymphoma and other malignancies. 23 HDACi and other epigenetic modifying therapies (DNMT3A inhibitors) have now been studied in combination with PD-1 blockade for a number of cancers and there have been early clinical signs of potential synergy.…”

Section: Introductionmentioning

confidence: 99%

“… 23 HDACi and other epigenetic modifying therapies (DNMT3A inhibitors) have now been studied in combination with PD-1 blockade for a number of cancers and there have been early clinical signs of potential synergy. 21 , 25 , 26 In classic Hodgkin lymphoma (cHL), for example, the combination of PD-1 blockade with DNMT3Ai was associated with a higher CR rate and progression-free survival (PFS) compared to anti-PD-1 monotherapy. 25 , 26 We, therefore, hypothesized that adding the immunomodulatory pan-HDACi, vorinostat, to the anti-PD1 antibody, pembrolizumab, in patients with r/r FL, DLBCL, PMBL, and cHL would be safe and boost the anti-tumor activity of PD-1 blockade in B-cell lymphomas.…”

Section: Introductionmentioning

confidence: 99%

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Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma

et al. 2023

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Outcomes after programmed death-1 (PD-1) blockade in B-cell lymphomas are disappointing with few durable responses. Histone deacetylase inhibitors (HDACi) exhibit favorable immunomodulatory effects and demonstrate synergistic anti-tumor immune responses with anti-PD-1 therapy in pre-clinical models. We therefore developed a phase I study to evaluate the safety and preliminary efficacy of Pembrolizumab with Vorinostat in relapsed/refractory B-cell lymphomas. Patients were treated in a dose-escalation cohort using a Rolling 6 design followed by an expansion cohort at the recommended phase 2 dose (R2PD). Fifty-two patients were enrolled (32 Hodgkin and 20 non-Hodgkin lymphoma (NHL)). Here, we report safety data from the dose escalation cohort, and the toxicity and efficacy within NHL patients. Vorinostat was administered on twice daily on days 1-5 and 8-12 (dose-level (DL)1: 100mg; DL2: 200mg) and Pembrolizumab (200mg) was administered on day 1 of each 3-week cycle. Of 6 patients treated at DL1, 1 had a dose-limiting toxicity (DLT) (Stevens-Johnson syndrome (SJS)), and 1 of 6 had a DLT at DL2 (thromboembolism); therefore, DL2 was the RP2D. The patient developing SJS was treated with corticosteroids, infliximab, and cyclosporine but ultimately died of invasive fungal infection from the extensive immunosuppression used to treat the SJS. The most common adverse events were hypertension, diarrhea, and cytopenias. Of 20 NHL patients, 9 had follicular lymphoma (FL) and 11 had diffuse large B-cell lymphoma (DLBCL). Five DLBCL patients had primary mediastinal B-cell lymphoma (PMBL). The complete and overall response rates (CR and ORR) were 11%/22% for FL and 45%/55% for all DLBCL. Amongst DLBCLs, the CR and ORR was 80%/80% for PMBL and 17%/33% for non-PMBL. In conclusion, Pembrolizumab with Vorinostat was tolerable and produced responses in relapsed/refractory B-cell NHL, with particularly notable efficacy in PMBL.

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How can we establish animal models of HIV‐associated lymphoma?

Xiao,

Zhai,

Zhang

et al. 2024

Anim Models and Exp Med

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Human immunodeficiency virus (HIV) infection is strongly associated with a heightened incidence of lymphomas. To mirror the natural course of human HIV infection, animal models have been developed. These models serve as valuable tools to investigate disease pathobiology, assess antiretroviral and immunomodulatory drugs, explore viral reservoirs, and develop eradication strategies. However, there are currently no validated in vivo models of HIV‐associated lymphoma (HAL), hampering progress in this crucial domain, and scant attention has been given to developing animal models dedicated to studying HAL, despite their pivotal role in advancing knowledge. This review provides a comprehensive overview of the existing animal models of HAL, which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

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Histone deacetylases inhibitor chidamide synergizes with humanized PD1 antibody to enhance T-cell chemokine expression and augment Ifn-γ response in NK-T cell lymphoma

Cited by 8 publications

References 43 publications

Current Approaches to Epigenetic Therapy

Current Approaches to Epigenetic Therapy

Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma

How can we establish animal models of HIV‐associated lymphoma?

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