scholarly journals Immune checkpoint inhibition by anti-PDCD1 (anti-PD1) monoclonal antibody has significant therapeutic activity against central nervous system lymphoma in an immunocompetent preclinical model

2017 ◽  
Vol 183 (4) ◽  
pp. 674-678 ◽  
Author(s):  
Yushi Qiu ◽  
Zhimin Li ◽  
Frederic Pouzoulet ◽  
Prakash Vishnu ◽  
John A. Copland ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Monoclonal Antibody ◽  
Nervous System ◽  
Immune Checkpoint ◽  
Central Nervous System Lymphoma ◽  
Preclinical Model ◽  
Therapeutic Activity ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition

scholarly journals Neurosarcoidosis following Immune Checkpoint Inhibition

2018 ◽  
Vol 11 (2) ◽  
pp. 521-526 ◽  
Author(s):  
Anastasie M. Dunn-Pirio ◽  
Suma Shah ◽  
Christopher Eckstein
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Relevant Literature ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Cns Involvement ◽  
Cns Metastases

Recently, immune checkpoint inhibitors have revolutionized cancer care by enhancing anti-tumor immunity. However, by virtue of stimulating the immune system, they can lead to immune-related adverse events (irAEs). Neurologic irAEs are uncommon but are becoming increasingly recognized and can be quite serious or even fatal. Furthermore, central nervous system (CNS) manifestations may be difficult to distinguish from CNS metastases, posing management challenges. Here, we describe a patient who developed exacerbation of sarcoidosis leading to CNS involvement following dual checkpoint blockade with nivolumab and ipilimumab for metastatic melanoma and review the relevant literature.

A pilot study of immune checkpoint inhibition (tremelimumab and/or MEDI4736) in combination with radiation therapy in patients with unresectable pancreatic cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS470-TPS470
Author(s):  
Austin G. Duffy ◽  
Oxana V. Makarova-Rusher ◽  
Drew Pratt ◽  
David E Kleiner ◽  
Christine Alewine ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Monoclonal Antibody ◽  
Radiation Therapy ◽  
Pilot Study ◽  
Immune Checkpoint ◽  
Human Monoclonal Antibody ◽  
Unresectable Pancreatic Cancer ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Early Stage Disease

TPS470 Background: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and causes inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. MEDI4736 is a human monoclonal antibody directed against PD-L1. Blockage of ligation between PD-L1 and PD1 induces local immune activation and prevents anergy and exhaustion of effector T-cells. Several studies have documented an increase in peripheral antitumor immunity following radiation. This effect is evidently too weak to be clinically relevant, but has the potential to be boosted by immune modulation. The underlying hypothesis of this study is that the effect of immune checkpoint inhibition (accomplished via tremelimumab and/or MEDI4736) treatment can be enhanced by radiation in patients with advanced pancreatic carcinoma. Whilst radiation treatment in pancreas cancer is commonly employed in limited or early stage disease, if radiation can enhance the effect of immune checkpoint inhibition to produce systemic anti-tumor effects the combination could become an effective treatment modality for patients with advanced disease. Methods: Patients with histologically confirmed metastatic pancreatic cancer with primary in-situ (or locally-recurrent) disease are being enrolled to this pilot study. The primary objectives are to determine the safety, tolerability and feasibility of immune checkpoint inhibition [comprising either MEDI4736 alone (Cohort A), Tremelimumab (Cohort B) or combined MEDI4736 and Tremelimumab (Cohort C)] in combination with stereotactic body radiation therapy (SBRT) in patients with unresectable pancreatic cancer. Select eligibility criteria are as follows: at least 1 measurable metastatic lesion by RECIST 1.1 criteria and accessible for biopsy. No prior radiation therapy to the pancreas allowed. There is no limit to the number of prior chemotherapy regimens received; ECOG ≤ 1; Life expectancy of greater than 3 months. Acceptable organ and bone marrow function. No active or prior documented autoimmune or inflammatory disorders. Clinical trial information: NCT02311361.

A pilot study of immune checkpoint inhibition in combination with radiation therapy in patients with metastatic pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15786-e15786 ◽  
Author(s):  
Austin G. Duffy ◽  
Oxana V. Makarova-Rusher ◽  
David E Kleiner ◽  
Christine Alewine ◽  
William Douglas Figg ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Monoclonal Antibody ◽  
Radiation Therapy ◽  
Pilot Study ◽  
Immune Checkpoint ◽  
Advanced Pancreatic Cancer ◽  
Primary Objective ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Eligibility Criteria

e15786 Background: Durvalumab is a human IgG1 monoclonal antibody directed against PD-L1. Tremelimumab is a selective human IgG2 monoclonal antibody against CTLA-4. Several studies have documented an increase in peripheral antitumor immunity following radiation. The hypothesis of this study is that the effect of immune checkpoint inhibition (ICI) can be enhanced by radiation in pancreatic adenocarcinoma (PAC). Methods: Patients with histologically confirmed metastatic PC with primary in-situ or metastatic SBRT-amenable disease are being enrolled to this pilot study. Primary objective to determine safety, tolerability and feasibility of immune checkpoint inhibition [comprising either Durvalumab alone (Cohort A), or combined durvalumab and tremelimumab (Cohort B)] in combination with stereotactic body radiation therapy (SBRT) at two different schedules (8Gy/single fraction or 25Gy in 5 fractions). Select eligibility criteria are as follows: at least 1 measurable metastatic lesion by RECIST 1.1 accessible for biopsy. No limit to the number of prior chemotherapy regimens; ECOG ≤ 1; Life expectancy of greater than 3 months. Acceptable organ and bone marrow function. No active autoimmune disorders. Results: N = 24 patients with chemorefractory metastatic PC have so far been enrolled; M/F = 13/11; Median age = 61. Treatment was well tolerated. No DLT encountered. The most common toxicity was fatigue (G1/2) in all patients in DL2. 5/24 pts had early discontinuation ( < 4 wks) due to rapid PD. No objective responses have been seen. 5 pts (21%) had SD as best response. Conclusions: Immune checkpoint inhibition in combination with SBRT in advanced pancreatic cancer is safe and feasible. Preliminarily no objective responses have been seen for these schedules of SBRT with durvalumab. The study is continuing with evaluation of SBRT with dual checkpoint inhibition (durvalumab and tremelimumab). Clinical trial information: NCT02311361.

In-depth characterization of the tumor microenvironment in central nervous system lymphoma reveals implications for immune-checkpoint therapy

2020 ◽  
Vol 69 (9) ◽  
pp. 1751-1766 ◽  
Author(s):  
Lukas Marcelis ◽  
Asier Antoranz ◽  
Anne-Marie Delsupehe ◽  
Pauline Biesemans ◽  
Julio Finalet Ferreiro ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tumor Microenvironment ◽  
Immune Checkpoint ◽  
Central Nervous System Lymphoma
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