scholarly journals Finding and characterizing a catalytic antibody light chain, H34, capable of degrading the PD-1 molecule

2021 ◽  
Author(s):  
Emi Hifumi ◽  
Hiroaki Taguchi ◽  
Tamami Nonaka ◽  
Takunori Harada ◽  
Taizo Uda
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Light Chain ◽  
Immune Checkpoint ◽  
Cell Function ◽  
Catalytic Antibody ◽  
T Cell Function ◽  
Programmed Cell Death 1

Programmed cell death 1 (PD-1) is an immune checkpoint regulating T-cell function. A catalytic antibody light chain, H34, could enzymatically degrade the PD-1 molecule. In addition, it inhibited the binding of PD-1 with PD-L1.

scholarly journals Classical Hodgkin’s Lymphoma in the Era of Immune Checkpoint Inhibition

2019 ◽  
Vol 8 (10) ◽  
pp. 1596 ◽  
Author(s):  
De Re ◽  
Caggiari ◽  
Repetto ◽  
Mussolin ◽  
Mascarin
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Janus Kinase ◽  
Cell Dysfunction ◽  
Cell Responses ◽  
Programmed Cell Death 1 ◽  
T Cell Dysfunction

: The ligation of programmed cell death 1 (PD-1) with programmed cell death ligand PD-L activates the immune checkpoint leading to T-cell dysfunction, exhaustion, and tolerance, especially in Hodgkin lymphoma (HL) where the PD-L/ Janus kinase (Jak) signaling was frequently found altered. Anti-PD-1 or anti-PD-L1 monoclonal antibodies can reverse this immune checkpoint, releasing the brake on T-cell responses. The characterization of the mechanisms regulating both the expression of PD-1 and PD-L and their function(s) in HL is ongoing. We provide in this review the recent findings focused on this aim with special attention on the major research topics, such as adverse events and resistance to PD-1–PD-L1 inhibitor treatment, together with a part about angiogenesis, extracellular vesicles, and microbiome in HL pathogenesis.

scholarly journals Co-delivery of IOX1 and doxorubicin for antibody-independent cancer chemo-immunotherapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Liu ◽  
Zhihao Zhao ◽  
Nasha Qiu ◽  
Quan Zhou ◽  
Guowei Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Memory Function ◽  
Histone Demethylase ◽  
Cell Dysfunction ◽  
T Cell Infiltration ◽  
Programmed Cell Death 1 ◽  
T Cell Dysfunction

AbstractAnti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) antibodies are currently used in the clinic to interupt the PD-1/PD-L1 immune checkpoint, which reverses T cell dysfunction/exhaustion and shows success in treating cancer. Here, we report a histone demethylase inhibitor, 5-carboxy-8-hydroxyquinoline (IOX1), which inhibits tumour histone demethylase Jumonji domain-containing 1A (JMJD1A) and thus downregulates its downstream β-catenin and subsequent PD-L1, providing an antibody-independent paradigm interrupting the PD-1/PD-L1 checkpoint. Synergistically, IOX1 inhibits cancer cells’ P-glycoproteins (P-gp) through the JMJD1A/β-catenin/P-gp pathway and greatly enhances doxorubicin (DOX)-induced immune-stimulatory immunogenic cell death. As a result, the IOX1 and DOX combination greatly promotes T cell infiltration and activity and significantly reduces tumour immunosuppressive factors. Their liposomal combination reduces the growth of various murine tumours, including subcutaneous, orthotopic, and lung metastasis tumours, and offers a long-term immunological memory function against tumour rechallenging. This work provides a small molecule-based potent cancer chemo-immunotherapy.

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