Anti-CD30 chimeric antigen receptor T cell therapy for relapsed/refractory CD30+ lymphoma patients

Wang, D.; Zeng, Cui; Xu, Bin; Xu, Jian; Wang, Jin; Jiang, Lijun; Wang, Q.-X.; Li, C.-R.; Wang, N.; Huang, Liang; Zhang, Y.-C.; Xiao, Yi; Zhou, Jianfeng

doi:10.1038/s41408-020-0274-9

Cited by 40 publications

(46 citation statements)

References 15 publications

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“…Hodgkin lymphoma (HL) affects around 80,000 people worldwide each year, accounting for around 0.4% of all cancers. 1 HL is a very common cancer in young adolescents (15)(16)(17)(18)(19) years old), amounting to 12% of all cancers in this age group in the United States. 2 The standard diagnosis and classification of HL are based on the morphological and immunohistochemical identification of the Hodgkin and Reed-Sternberg (HRS) cells in excisional biopsies.…”

Section: Hodgkin Lymphomamentioning

confidence: 99%

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The role of trogocytosis in immune surveillance of Hodgkin lymphoma

Zeng

Schwarz

2020

OncoImmunology

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Hodgkin lymphoma (HL) is a unique type of hematopoietic cancer that has few tumor cells but a massive infiltration of immune cells. Findings on how the cancerous Hodgkin and Reed-Sternberg (HRS) cells survive and evade immune surveillance have facilitated the development of novel immunotherapies for HL. Trogocytosis is a fast process of intercellular transfer of membrane patches, which can significantly affect immune responses. In this review, we summarize the current knowledge of how trogocytosis contributes to the suppression of immune responses in HL. We focus on the ectopic expression of CD137 on HRS cells, the cause of its expression, and its implication on developing novel therapies for HL. Further, we review data demonstrating that similar mechanisms apply to CD30, PD-L1 and CTLA-4.

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Section: Hodgkin Lymphomamentioning

confidence: 99%

“…Brentuximab vedotin (an anti-CD30-drug conjugate) and anti-PD-1 antibodies achieve good objective response rates (>50%) in r/r HL. 12 , 14 Other immunotherapies, such as chimeric antigen receptor T (CAR-T) cells, 15 – 18 are attracting intense research interest. 19 …”

Section: Hodgkin Lymphomamentioning

confidence: 99%

The role of trogocytosis in immune surveillance of Hodgkin lymphoma

Zeng

Schwarz

2020

OncoImmunology

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“…In another study, pharmacological blocking of HSP90 resulted in decreased expression of Linker FIGURE 2 | HSPs and CAR T/NK cells in lymphoma immunotherapy. Chimeric Antigens Receptor (CAR) targeting CD19 and CD30 showed promising results in patients with r/r lymphoma (93,129,131,132). Autologous NK cells pre-activated with cytokines (IL-2, IL-15) and 14-mer HSP70-derived peptide (TKD) can be used for ex vivo activation of NK cells for the adoptive transfer therapy (137)(138)(139)(140).…”

Section: Hsps and Emerging Lymphoma Immunotherapymentioning

confidence: 99%

“…Cytokine release syndrome (CRS) and skin rash that occurred in 10 and 20 patients, respectively, were found to be associated with cyclophosphamide rather than with bendamustine and both spontaneously resolved ( 131 ). In another study, Wang and colleagues designed anti-CD30 CAR and conducted a pilot study in patients with r/r Hodgkin lymphoma ( 132 ). After lymphodepletion, patients were infused with anti-CD30 CAR Ts.…”

Section: Hsps and Emerging Lymphoma Immunotherapymentioning

confidence: 99%

“…After lymphodepletion, patients were infused with anti-CD30 CAR Ts. A total of 9 patients received CD30 CAR T infusion, 3 achieved CR, six experienced CRS from which 4 were low-grade and no neurotoxicity was observed ( 132 ). Authors also demonstrated promising results in combination therapy where CD30 CAR T treatment was combined with anti-PD-1 antibody ( 132 ).…”

Section: Hsps and Emerging Lymphoma Immunotherapymentioning

confidence: 99%

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Heat Shock Proteins in Lymphoma Immunotherapy

2021

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Immunotherapy harnessing the host immune system for tumor destruction revolutionized oncology research and advanced treatment strategies for lymphoma patients. Lymphoma is a heterogeneous group of cancer, where the central roles in pathogenesis play immune evasion and dysregulation of multiple signaling pathways. Immunotherapy-based approaches such as engineered T cells (CAR T), immune checkpoint modulators and NK cell-based therapies are now in the frontline of lymphoma research. Even though emerging immunotherapies showed promising results in treating lymphoma patients, low efficacy and on-target/off-tumor toxicity are of a major concern. To address that issue it is suggested to look into the emerging role of heat shock proteins. Heat shock proteins (HSPs) showed to be highly expressed in lymphoma cells. HSPs are known for their abilities to modulate immune responses and inhibit apoptosis, which made their successful entry into cancer clinical trials. Here, we explore the role of HSPs in Hodgkin and Non-Hodgkin lymphoma and their involvement in CAR T therapy, checkpoint blockade and NK cell- based therapies. Understanding the role of HSPs in lymphoma pathogenesis and the ways how HSPs may enhance anti-tumor responses, may help in the development of more effective, specific and safe immunotherapy.

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Design, Synthesis, and Targeted Delivery of an Immune Stimulant that Selectively Reactivates Exhausted CAR T Cells

et al. 2022

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Although chimeric antigen receptor (CAR) T cells have demonstrated significant promise in suppressing hematopoietic cancers, their applications in treating solid tumors have been limited by onset of CAR T cell exhaustion that accompanies continuous CAR T cell exposure to tumor antigen. To address this limitation, we have exploited the abilities of recently designed universal CARs to bind fluorescein and internalize a fluorescein-TLR7 agonist conjugate by CAR-mediated endocytosis. We demonstrate here that anti-fluorescein CAR-mediated uptake of a fluorescein-TLR7-3 conjugate can reactivate exhausted CAR T cells, leading to dramatic reduction in T cell exhaustion markers (PD-1 + Tim-3 + ) and shrinkage of otherwise resistant tumors without inducing systemic activation of the immune system. We conclude that CAR T cell exhaustion can be reversed by administration of a CAR-targeted TLR7 agonist, thereby enabling the CAR T cells to successfully treat solid tumors without incurring the systemic toxicity that commonly accompanies administration of nontargeted TLR7 agonists.

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Anti-CD30 chimeric antigen receptor T cell therapy for relapsed/refractory CD30+ lymphoma patients

Cited by 40 publications

References 15 publications

The role of trogocytosis in immune surveillance of Hodgkin lymphoma

The role of trogocytosis in immune surveillance of Hodgkin lymphoma

Heat Shock Proteins in Lymphoma Immunotherapy

Design, Synthesis, and Targeted Delivery of an Immune Stimulant that Selectively Reactivates Exhausted CAR T Cells

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