scholarly journals 526 Removal of soluble tumor necrosis factors receptors 1/2 in patients with metastatic solid tumors using immune apheresis

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A556-A556
Author(s):  
Ayala Tamir ◽  
Hagit Harati ◽  
Nethanel Asher ◽  
Ronen Stoff ◽  
Shirly Grynberg ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Central Line ◽  
Affinity Column ◽  
Mass Cytometry ◽  
Cytokine Detection ◽  
Full Study ◽  
Immuno Assay ◽  
Differential Increase

BackgroundTNFα is a cytokine produced by immune cells and by tumor cells. The soluble forms of membrane TNF receptors 1/2 (sTNF-R1/2) act as decoy to neutralize TNFα, and are highly abundant in cancer patients. Elimination of sTNF-R1/2 may therefore unmask endogenous TNFα, to presumably exert anti-neoplastic effects and reverse resistance to immune checkpoint inhibitors. Immune Apheresis (IA) is a procedure designed to specifically capture sTNF-R1/2 from plasma by passing it over an affinity column. Here we employed Immunicom’s LW-02 Immunopheresis® device for removal of sTNF-R1/2 from plasma of cancer patients.MethodsIn cohort A, patients with melanoma, RCC, NSCLC or TNBC refractory to standard therapy were treated with IA only. IA treatment of 2 plasma volumes was done x3/week, for three treatment cycles (4 weeks each) up to a total of 36 treatments. Cohort B patients currently receive concurrent IA and Nivolumab therapy (240mg q2 weeks starting on week 5). sTNF-Rs removal and circulating inflammatory biomarkers were measured by immuno-assays, such as multiplex cytokine detection and mass cytometry. Pre- and post-treatment tumor biopsies were analyzed for tumor markers and TILs by immunohistochemistry.ResultsCohort A included six patients (3 Melanoma and 3 TNBC): three patients completed full study regimen, and three others were withdrawn due to clinical progression. AEs included chills (4/6), fever (2/6), anemia (6/6), central line thrombosis (1/6) and pulmonary embolism (1/6) All were Grade 2 except G3 anemia (1/6). There were no treatment related SAE’s. sTNF-Rs levels were significantly reduced, followed by enhanced detection of TNFα, and IFNγ in some cases. In two patients, CD8 counts and PD-1 and PD-L1 expression were increased. Congruently, blood mass cytometry showed reduction in Treg subsets and differential increase of CD8 subsets following treatment.ConclusionsThe use of Immunicom’s LW-02 Immunopheresis® device in combination with Terumo BCT Spectra Optia Apheresis System is safe and efficient in the removal of sTNF-Rs from blood plasma. Subsequent immuno-assay analyses indicated formation of inflammatory response which may facilitate effects of immunotherapy, yet to be investigated in cohort B.Trial RegistrationNCT04142931Ethics ApprovalSheba Medical Center Ethics Committee, 6136-19ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal

scholarly journals The Ratio of IP10 to IL-8 in Plasma Reflects and Predicts the Response of Patients With Lung Cancer to Anti-PD-1 Immunotherapy Combined With Chemotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Liangliang Wu ◽  
Shengzhi Xie ◽  
Lingxiong Wang ◽  
Jinfeng Li ◽  
Lu Han ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Checkpoint Inhibitors ◽  
Multiple Cancer ◽  
Lung Cancer Patients ◽  
Multiple Cancers ◽  
Cytokine Detection ◽  
Specificity And Sensitivity ◽  
Number Of Patients

Antibodies against checkpoint inhibitors such as anti-programmed cell death protein 1 (PD-1) and its ligand anti-programmed death ligand 1 (PD-L1) have shown clinical efficacy in the treatment of multiple cancers. However, there are only a few studies on biomarkers for these targeted immunotherapies, especially in peripheral blood. We first studied the role of interferon-induced protein-10 (IP10) combined with interleukin-8 (IL-8) in peripheral blood as a biomarker of immune-combined chemotherapy for lung cancer and multiple cancers. We used the high-throughput cytokine detection platform and performed bioinformatics analysis of blood samples from 67 patients with lung cancer and 24 with multiple cancers. We selected the ratio of IP-10 to IL-8 (S2/S0, ratio of changes at 10–12 weeks after treatment to baseline) to predict the response to immunotherapy combined with chemotherapy and evaluate the survival of lung cancer patients and mixed cancer patients. In patients treated with the combination therapy, the specificity and sensitivity of IL-8 and IP10 together as predictors were improved compared with those of IL-8 and IP10 alone. Our conclusion was verified in not only lung cancer but also multiple cancer research cohorts. We then further validated the predictive effect of biomarkers in different histologic types of NSCLC and chemotherapy combined with different PD-1 drug groups. Subsequent validation should be conducted with a larger number of patients. The proposed marker IP10 (S2/S0)/IL-8 (S2/S0), as a predictive immunotherapy biomarker, has broad prospects for future clinical applications in treating patients with multiple intractable neoplasms.

scholarly journals A digital single-molecule nanopillar SERS platform for predicting and monitoring immune toxicities in immunotherapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Junrong Li ◽  
Alain Wuethrich ◽  
Abu A. I. Sina ◽  
Han-Hao Cheng ◽  
Yuling Wang ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Single Molecule ◽  
Immune Checkpoint ◽  
Inflammatory Responses ◽  
Checkpoint Inhibitors ◽  
Cytokine Detection ◽  
Dynamic Tracking ◽  
Highly Sensitive ◽  
Life Threatening ◽  
Melanoma Patients

AbstractThe introduction of immune checkpoint inhibitors has demonstrated significant improvements in survival for subsets of cancer patients. However, they carry significant and sometimes life-threatening toxicities. Prompt prediction and monitoring of immune toxicities have the potential to maximise the benefits of immune checkpoint therapy. Herein, we develop a digital nanopillar SERS platform that achieves real-time single cytokine counting and enables dynamic tracking of immune toxicities in cancer patients receiving immune checkpoint inhibitor treatment - broader applications are anticipated in other disease indications. By analysing four prospective cytokine biomarkers that initiate inflammatory responses, the digital nanopillar SERS assay achieves both highly specific and highly sensitive cytokine detection down to attomolar level. Significantly, we report the capability of the assay to longitudinally monitor 10 melanoma patients during immune inhibitor blockade treatment. Here, we show that elevated cytokine concentrations predict for higher risk of developing severe immune toxicities in our pilot cohort of patients.

scholarly journals Incidence of Skin and Respiratory Immune-Related Adverse Events Correlates With Specific Tumor Types in Patients Treated With Checkpoint Inhibitors

2021 ◽  
Vol 10 ◽  
Author(s):  
Lynn M. Rose ◽  
Hannah A. DeBerg ◽  
Prakash Vishnu ◽  
Jason K. Frankel ◽  
Adarsh B. Manjunath ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Specific Response ◽  
Specific Tumor ◽  
Wide Range ◽  
Diverse Patient Population ◽  
Pre Treatment ◽  
Grade 3

Checkpoint inhibitors (CPIs) increase antitumor activity by unblocking regulators of the immune response. This action can provoke a wide range of immunologic and inflammatory side effects, some of which can be fatal. Recent studies suggest that CPI-induced immune-related adverse events (irAEs) may predict survival and response. However, little is known about the mechanisms of this association. This study was undertaken to evaluate the influence of tumor diagnosis and preexisting clinical factors on the types of irAEs experienced by cancer patients treated with CPIs. The correlation between irAEs and overall survival (OS) was also assessed. All cancer patients treated with atezolizumab (ATEZO), ipilimumab (IPI), nivolumab (NIVO), or pembrolizumab (PEMBRO) at Virginia Mason Medical Center between 2011 and 2019 were evaluated. irAEs were graded according to the Common Terminology Criteria for Adverse Events (Version 5) and verified independently. Statistical analyses were performed to assess associations between irAEs, pre-treatment factors, and OS. Of the 288 patients evaluated, 59% developed irAEs of any grade, and 19% developed irAEs of grade 3 or 4. A time-dependent survival analysis demonstrated a clear association between the occurrence of irAEs and OS (P < 0.001). A 6-week landmark analysis adjusted for body mass index confirmed an association between irAEs and OS in non-Small Cell Lung Cancer (NSCLC) (P < 0.03). An association between melanoma and skin irAEs (P < 0.01) and between NSCLC and respiratory irAEs (P = 0.03) was observed, independent of CPI administered. Patients with preexisting autoimmune disease experienced a higher incidence of severe irAEs (P = 0.01), but not a higher overall incidence of irAEs (P = 0.6). A significant association between irAEs and OS was observed in this diverse patient population. No correlation was observed between preexisting comorbid conditions and the type of irAE observed. However, a correlation between skin-related irAEs and melanoma and between respiratory irAEs and NSCLC was observed, suggesting that many irAEs are driven by a specific response to the primary tumor. In patients with NSCLC, the respiratory irAEs were associated with a survival benefit.

scholarly journals Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 86
Author(s):  
Mohit Kumar ◽  
Chellappagounder Thangavel ◽  
Richard C. Becker ◽  
Sakthivel Sadayappan
Keyword(s):  
Cancer Patients ◽  
Immune Modulation ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Induced Pluripotent Stem Cell ◽  
High Volume ◽  
Oncolytic Viruses ◽  
Model Systems ◽  
Volume Data ◽  
Late Cardiotoxicity

Immunotherapy is one of the most effective therapeutic options for cancer patients. Five specific classes of immunotherapies, which includes cell-based chimeric antigenic receptor T-cells, checkpoint inhibitors, cancer vaccines, antibody-based targeted therapies, and oncolytic viruses. Immunotherapies can improve survival rates among cancer patients. At the same time, however, they can cause inflammation and promote adverse cardiac immune modulation and cardiac failure among some cancer patients as late as five to ten years following immunotherapy. In this review, we discuss cardiotoxicity associated with immunotherapy. We also propose using human-induced pluripotent stem cell-derived cardiomyocytes/ cardiac-stromal progenitor cells and cardiac organoid cultures as innovative experimental model systems to (1) mimic clinical treatment, resulting in reproducible data, and (2) promote the identification of immunotherapy-induced biomarkers of both early and late cardiotoxicity. Finally, we introduce the integration of omics-derived high-volume data and cardiac biology as a pathway toward the discovery of new and efficient non-toxic immunotherapy.

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