scholarly journals Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1443
Author(s):  
Leonie D. H. Gossel ◽  
Catrin Heim ◽  
Lisa-Marie Pfeffermann ◽  
Laura M. Moser ◽  
Halvard B. Bönig ◽  
...  
Keyword(s):  
High Risk ◽  
Tumor Cells ◽  
Chimeric Antigen Receptor ◽  
Treatment Options ◽  
Antigen Receptor ◽  
Proof Of Concept ◽  
Cell Monolayers ◽  
Novel Treatment ◽  
Dismal Prognosis

The dismal prognosis of pediatric and young adult patients with high-risk rhabdomyosarcoma (RMS) underscores the need for novel treatment options for this patient group. In previous studies, the tumor-associated surface antigen ERBB2 (HER2/neu) was identified as targetable in high-risk RMS. As a proof of concept, in this study, a novel treatment approach against RMS tumors using a genetically modified natural killer (NK)-92 cell line (NK-92/5.28.z) as an off-the-shelf ERBB2-chimeric antigen receptor (CAR)-engineered cell product was preclinically explored. In cytotoxicity assays, NK-92/5.28.z cells specifically recognized and efficiently eliminated RMS cell suspensions, tumor cell monolayers, and 3D tumor spheroids via the ERBB2-CAR even at effector-to-target ratios as low as 1:1. In contrast to unmodified parental NK-92 cells, which failed to lyse RMS cells, NK-92/5.28.z cells proliferated and became further activated through contact with ERBB2-positive tumor cells. Furthermore, high amounts of effector molecules, such as proinflammatory and antitumoral cytokines, were found in cocultures of NK-92/5.28.z cells with tumor cells. Taken together, our data suggest the enormous potential of this approach for improving the immunotherapy of treatment-resistant tumors, revealing the dual role of NK-92/5.28.z cells as CAR-targeted killers and modulators of endogenous adaptive immunity even in the inhibitory tumor microenvironment of high-risk RMS.

The Prognostic Role of Circulating Tumor Cells (CTC) in High-risk Non–muscle-invasive Bladder Cancer

2017 ◽  
Vol 15 (4) ◽  
pp. e661-e666 ◽  
Author(s):  
Gian Maria Busetto ◽  
Matteo Ferro ◽  
Francesco Del Giudice ◽  
Gabriele Antonini ◽  
Benjamin I. Chung ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Invasive Bladder Cancer ◽  
Prognostic Role ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals Noninferior Antibiotics: When Is “Not Bad” “Good Enough”?

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Mark J. DiNubile
Keyword(s):  
Nursing Home ◽  
Clinical Practice ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Chronically Ill ◽  
Multidrug Resistant ◽  
Everyday Clinical Practice ◽  
Novel Treatment ◽  
Efficacious Treatment

Abstract Novel treatment options are urgently needed for patients with serious multidrug-resistant infections seen increasingly in routine everyday clinical practice, both in the hospital and nursing home as well as in the clinic and office setting. Unfortunately, the problem is no longer confined to chronically ill, repeatedly hospitalized patients. This essay explores the role of noninferiorly studies in addressing the pressing need for new antimicrobial agents to combat the emerging “superbugs”, calling attention to the nuances of interpreting their sometimes less-than-straightforward results. The overriding aim is not to find better antibiotics for routinely treatable infections but to identify safe and efficacious treatment options where none presently exist.

scholarly journals ROR1-Specific Chimeric Antigen Receptor (CAR) NK Cell Immunotherapy for High Risk Neuroblastomas and Sarcomas

2017 ◽  
Vol 23 (3) ◽  
pp. S136-S137 ◽  
Author(s):  
Haein Park ◽  
Aradhana Awasthi ◽  
Janet Ayello ◽  
Yaya Chu ◽  
Stanley Riddell ◽  
...  
Keyword(s):  
High Risk ◽  
Chimeric Antigen Receptor ◽  
Nk Cell ◽  
Antigen Receptor ◽  
Cell Immunotherapy

scholarly journals Role of bridging therapy during chimeric antigen receptor T cell therapy

eJHaem ◽  
2021 ◽  
Author(s):  
Shakthi T. Bhaskar ◽  
Bhagirathbhai R. Dholaria ◽  
Salyka M. Sengsayadeth ◽  
Bipin N. Savani ◽  
Olalekan O. Oluwole
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Bridging Therapy ◽  
T Cell Therapy

Therapeutics and Research Related to Glioblastoma: Advancements and Future Targets

2020 ◽  
Vol 21 (3) ◽  
pp. 186-198 ◽  
Author(s):  
Vishal Chavda ◽  
Vimal Patel ◽  
Dhananjay Yadav ◽  
Jigar Shah ◽  
Snehal Patel ◽  
...  
Keyword(s):  
Treatment Options ◽  
Graphene Quantum Dots ◽  
Primary Brain Tumor ◽  
In Vitro Models ◽  
Molecular Pathways ◽  
Dismal Prognosis ◽  
Novel Drugs

Glioblastoma, the most common primary brain tumor, has been recognized as one of the most lethal and fatal human tumors. It has a dismal prognosis, and survival after diagnosis is less than 15 months. Surgery and radiotherapy are the only available treatment options at present. However, numerous approaches have been made to upgrade in vivo and in vitro models with the primary goal of assessing abnormal molecular pathways that would be suitable targets for novel therapeutic approaches. Novel drugs, delivery systems, and immunotherapy strategies to establish new multimodal therapies that target the molecular pathways involved in tumor initiation and progression in glioblastoma are being studied. The goal of this review was to describe the pathophysiology, neurodegeneration mechanisms, signaling pathways, and future therapeutic targets associated with glioblastomas. The key features have been detailed to provide an up-to-date summary of the advancement required in current diagnosis and therapeutics for glioblastoma. The role of nanoparticulate system graphene quantum dots as suitable therapy for glioblastoma has also been discussed.

Development of human NKG2D-CD3ε chimeric antigen receptor (CAR) for T-cell-mediated cancer immunotherapy.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 150-150
Author(s):  
Sergei Kusmartsev ◽  
Johaness Vieweg ◽  
Victor Prima
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Adaptor Protein ◽  
T Cell Subsets ◽  
Human T Cells

150 Background: NKG2D is a lectin-like type 2 transmembrane receptor that expressed by natural killer cells and some T cell subsets. Stimulation of NKG2D receptor with specific agonistic ligands produces activating signals through signaling adaptor protein DAP10 leading to the enhanced cytokine production, proliferation, and cytotoxicity against tumor cells. There is strong evidence that NKG2D ligands are expressed in many human tumors, including melanoma, leukemia, myeloma, glioma, and carcinomas of the prostate, breast, lung, and colon. Recent studies also demonstrated that T cells bearing chimeric antigen receptor (CAR) NKG2D linked to CD3ζ (zeta) chain produce marked in vitro and in vivo anti-tumor effects. The aim of current study was to determine whether human T cells bearing chimeric antigen receptor (CAR) NKGD2 linked to CD3ε (epsilon) chain could be activated by the NKG2D-specific stimulation and able to kill human cancer cells. Given the important role of CD3ε in activation and survival of T cells, we hypothesized that NKG2D-CDε-bearing T cells could exert strong in vitro and in vivo anti-tumor effects. Methods: NKG2D CAR was produced by linking human NKG2D to DAP10 and the cytoplasmic portion of the CD3ε chain. Original full-length human cDNA clones were obtained from NIH Mammalian Gene Collection (MGC). Functional domain analysis and oligonucleotide design in the in-Fusion system of DNA cloning (Clontech) was used to generate the retroviral expression constructs. Results: Human PBMC-derived T cells were retrovirally transduced with newly generated NKG2D-CD3ε CAR DNA construct. These NKG2D CAR-expressing human T cells responded to NKG2D-specific activation by producing IFN-γ and exhibited significant cellular cytotoxicity against human tumor cells in vitro. In vivo studies demonstrated that NKG2D-CD3ε-bearing cells are capable of inhibiting growth of DU-145 human prostate cancer in the immunodeficient mice. Conclusions: Collectively, our data indicate the feasibility of developing chimeric antigen receptor NKG2D-CD3ε for T cells and suggest that adoptive transfer of T cells bearing NKG2D-CD3ε CAR could be potentially effective for immunotherapy of cancer patients.

Rabies encephalitis

2021 ◽  
Vol 14 (4) ◽  
pp. e239249
Author(s):  
Shyam Chand Chaudhary ◽  
Akash Khandelwal ◽  
Ruchika Tandon ◽  
Kamal Kumar Sawlani
Keyword(s):  
Point Of Care ◽  
Treatment Options ◽  
Diagnostic Testing ◽  
Care Facility ◽  
Solid Organ ◽  
Mri Findings ◽  
Dismal Prognosis ◽  
Corneal Transplants ◽  
History Of

Rabies is an almost always fatal disease that physicians and patients dread due to its dismal prognosis and limited treatment options. Transmission of this disease occurs through the bite of dogs and wild animals (like jackal in our case). Other rare forms of transmission may be through inhalation in bat-infested caves and human-to-human transmission by infected corneal transplants, solid organ and tissue transplantation, and sometimes in laboratory settings. Its diagnosis is usually clinical in the absence of availability of special laboratory investigations at the point-of-care facility. Few people have described the role of imaging in diagnosis. We hereby report a patient with rabies encephalitis, having a history of jackal bite and classical MRI findings that we can use for early diagnosis in the absence of typical clinical features and specialised diagnostic testing.

A chimeric antigen receptor for TRAIL-receptor 1 induces apoptosis in various types of tumor cells

2014 ◽  
Vol 453 (4) ◽  
pp. 798-803 ◽  
Author(s):  
Eiji Kobayashi ◽  
Hiroyuki Kishi ◽  
Tatsuhiko Ozawa ◽  
Hiroshi Hamana ◽  
Hidetoshi Nakagawa ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Trail Receptor
Sign in / Sign up

Export Citation Format

Share Document