CAR-Engineered NK Cells for the Treatment of Glioblastoma: Turning Innate Effectors Into Precision Tools for Cancer Immunotherapy

Glioblastoma (GB) is the most common and aggressive primary brain tumor in adults and currently incurable. Despite multimodal treatment regimens, median survival in unselected patient cohorts is
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Conclusions: This meta-analysis demonstrated that CD44 overexpression might be an unfavorable prognostic factor for CRC patients and could be used to predict poor differentiation, lymph node metastasis and distant metastasis. Introduction Although therapies for colorectal cancer (CRC) has improved in recent years, colorectal cancer is still the third most common cause of cancer related death worldwide (1). Metastasis are observed in 25% of patients at initial diagnosis and approximately 50% of patients will develop metastasis (2). Presently, the outcome prediction and the therapy schedule determination of CRC patie...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion Several TISC-based immunotherapeutic approaches are under development in various stages of preclinical studies. As outlined in this review article, a careful and more exhaustive genetic and metabolic understanding of TISC-associated phenotypes is critical to develop novel TISC based immunotherapies. Various components within the tumor microenvironment such as tumor cells, infiltrating immune cells, and supporting stromal cells impact the TISC metabolism. This unique metabolic profile leads to upregulation of certain enzymes and proteins such as ALDH1, CEP55, IDO COA1 etc., which can be utilized for development ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, our WGCNA analysis identified candidate prognostic biomarkers for further basic and clinical researches. Introduction Breast cancer is a frequently diagnosed malignancy and the leading cause of cancer death among females around the world, accounting for 24% of cancer diagnoses and 15% of cancer deaths in females. According to Global Cancer Statistics 2018, there will be nearly 2.1 million new cases diagnosed globally, with ~62 thousand deaths. The incident rates of breast cancer increased in most developing countries during last decades, resulting from a combination of social and economic factors, incl...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, we evaluated whether the combination of focused ultrasound (FUS) and microbubbles can improve adoptively NK-92MI cell infiltration into ovarian tumors through biodistribution, immunofluorescence, and flow cytometry. The treatment effects of using this strategy twice a week were explored. The potential molecular mechanism of FUS assisting NK cell therapy was also initially explored through evaluating the expression of ICAM1 and CX3CL1 by qRT-PCR. Our results indicated that FUS and microbubbles can improve NK-92MI cells’ infiltration into tumors, and the combination of FUS and NK-92MI cells had a better ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In conclusion, CAR-T treatment combined with intratumoral delivery of poly I:C resulted in synergistic antitumor activity. We thus provide a rationale to translate this immunotherapeutic strategy to solid tumors. Introduction Adoptive T cell immunotherapy has been demonstrated to be a new way to fight malignancies. In particular, T lymphocytes engineered to express chimeric antigen receptor (CAR) have shown great promise in treating hematological malignancies (1). CD19-targeted CAR-T cells have been approved by FDA to treat relapsed B cell acute lymphoblastic leukemia (B-ALL) and Diffuse Large B-cell lymphoma (DLBC...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: High dose lapatinib is tolerable when given intermittently and sequentially with capecitabine. Antitumor activity was noted in both CNS and non-CNS sites of disease. This novel administration regimen is feasible and efficacious in HER2-positive breast cancer patients with CNS metastasis and warrants further investigation. PMID: 30988080 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Conclusions: CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review. Introduction Chimeric antigen receptors and engineered T cell receptors (based on previously identified high affinity T cell receptors) function by redirecting T cells to a predefined tumor-specific (or tumor-associated) target. Most of these modifications use retroviral or lentiviral vectors to integrate the construct, and most of the receptors ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
We examined the following three conditions: DMEM high glucose which contained 4.5 mg/ml glucose, independent of serum, DMEM low glucose which contained 1.0 mg/ml glucose, independent of serum. And, DMEM no glucose which contained 0.0 mg/ml glucose, independent of serum. DMEM is referred to as glucose “free,” however some glucose was actually present due to the FBS. The glucose concentration in the FBS used was 1.04 mg/ml. We calculate 0.0937 mg/ml glucose was present in the media under all conditions due to the addition of serum. Quantification of ROS Levels ROS are widely evaluated in tissue culture using di...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
AbstractWhen distant metastases are discovered, it is important to determine receptor profiles of these lesions through histologic examination. However, brain metastasis sites are difficult to reach to be routinely biopsied. The purpose of this study was to determine expression profiles of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in breast cancer brain metastasis (BCBM) and the existence of discordance between primary breast cancer and brain metastasis. A total of 37 patients who underwent craniotomies for metastatic brain tumors arising from breast cancer at N...
Source: Journal of Neuro-Oncology - Category: Cancer & Oncology Source Type: research
Abstract Glioblastoma is an aggressive malignancy with a poor prognosis. The current standard of care for newly diagnosed glioblastoma patients includes surgery to the extent, temozolomide combined with radiotherapy, and alternating electric fields therapy. After recurrence, there is no standard therapy and survival is less than 9 months. Recurrent glioblastoma offers a unique opportunity to investigate new treatment approaches in a malignancy known for remarkable genetic heterogeneity, immunosuppressive microenvironment and partially permissive anatomical blood brain barrier (BBB). Results from three first-in-man...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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