Preclinical development of T-cell receptor-engineered T-cell therapy targeting the 5T4 tumor antigen on renal cell carcinoma

In this report, targeted single-cell RNA sequencing was performed on 5T4p17-specific T-cell clones to sequence the highly variable complementarity-determining region 3 (CDR3) of T-cell receptor α chain (TRA) and β chain (TRB) genes. Full-lengthTRA andTRB sequences were cloned into lentiviral vectors and transduced into CD8+ T-cells from healthy donors. Redirected effector T-cell function against 5T4p17 was measured by cytotoxicity and cytokine release assays. Seven uniqueTRA-TRB pairs were identified. All seven TCRs exhibited high expression on CD8+ T-cells with transduction efficiencies from 59 to 89%. TCR-transduced CD8+ T-cells demonstrated redirected cytotoxicity and cytokine release in response to 5T4p17 on  target-cells and killed 5T4+/HLA-A2+ kidney-, breast-, and colorectal-tumor cell lines as well as primary RCC tumor cells in vitro. TCR-transduced CD8+ T-cells also detected presentation of 5T4p17 inTAP1/2-deficient T2 target-cells. TCR-transduced T-cells redirected to recognize the 5T4p17 epitope from a broadly shared tumor antigen are of interest for future testing as a cellular immunotherapy strategy for HLA-A2+ subjects with 5T4+ tumors.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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RAS protein activator like 2 (RASAL2) belongs to the RAS GTPase-activating protein family and plays an important role in several cancers, including ovarian cancer, nasopharyngeal carcinoma, malignant astrocytoma, renal cell carcinoma, bladder cancer, colorectal cancer, liver cancer, triple-negative breast cancer, lung adenocarcinoma, and pancreatic ductal adenocarcinoma. Traditionally, RASAL2 has been regarded as a tumor suppressor but recent studies have found that it is an oncogene in specific types of cancer, such as colorectal cancer, liver cancer, triple-negative breast cancer, triple-negative/estrogen receptor-negati...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Abstract Cancer incidence rate has increased so much that it is the second leading cause of deaths worldwide after cardiovascular diseases. Sensitive and specific biomarkers are needed for an early diagnosis of cancer and in-time treatment. Recent studies have found that long non-coding RNAs (lncRNAs) participate in cancer tumorigenesis. LncRNA P73 antisense RNA 1T (TP73-AS1), also known as KIAA0495 and p53-dependent apoptosis modulator (PDAM), is located in human chromosomal band 1p36.32 and plays a crucial role in many different carcinomas. This review summarizes current findings on the role of TP73-AS1 and its ...
Source: Bioscience Reports - Category: Biomedical Science Authors: Tags: Biosci Rep Source Type: research
In conclusion, 5-HTR1B, 5-HTR2B, DRD1, and DRD2 show mRNA overexpression in a broad spectrum of common and rare cancers. 5-HTR2B protein is frequently highly expressed in human cancers, especially on endothelial cells. These findings support further investigation of especially 5HTR2B as a potential treatment target. PMID: 31478179 [PubMed - as supplied by publisher]
Source: Pathology Oncology Research - Category: Pathology Authors: Tags: Pathol Oncol Res Source Type: research
Abstract Myoferlin, a protein of the ferlin family, has seven C2 domains and exhibits activity in some cells, including myoblasts and endothelial cells. Recently, myoferlin was identified as a promising target and biomarker in non-small-cell lung cancer, breast cancer, pancreatic adenocarcinoma, hepatocellular carcinoma, colon cancer, melanoma, oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma, clear cell renal cell carcinoma and endometrioid carcinoma. This evidence indicated that myoferlin was involved in the proliferation, invasion and migration of tumour cells, the mechanism of which...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Studies have identified that the polymorphism rs10069690 of telomerase reverse transcriptase (TERT) is associated with cancer risk, but the results remain inconclusive. We performed a meta ‐analysis of 45 published studies including 329,035 cases and 730,940 controls. This meta‐analysis suggested that the TERT rs10069690 polymorphism may be a risk factor for cancer, especially breast cancer, ovarian cancer, and lung cancer. Further functional studies are warranted to reveal the ro le of the polymorphism in carcinogenesis. AbstractBackgroundStudies have identified that the telomerase reverse transcriptase (TERT) gene po...
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionsPET/CT, as a non-invasive method, can be preferred as the first choice in the detection of primary tumor in patients with BMUO.ResumenObjetivoEste trabajo analiza el papel de la PET/TC con 18F-FDG en la detección del tumor primario en pacientes con metástasis óseas de origen desconocido (MOOD).Material y MétodosEste estudio retrospectivo consideró al análisis histopatológico o el seguimiento clínico como datos de referencia en el diagnóstico de tumores primarios y estos resultados fueron comparados con los resultados de la PET/TC.ResultadosSe incluye...
Source: Revista Espanola de Medicina Nuclear e Imagen Molecular - Category: Nuclear Medicine Source Type: research
289Purpose: Recent development of quinoline based positron-emission-tomography (PET)-tracers that act as fibroblast-activation-protein inhibitors (FAPI) demonstrated promising preclinical and clinical results. FAP is overexpressed from cancer associated fibroblasts (CAFs) of several tumor entities. Here we quantify the tumor-uptake in FAPI-PET/CT of various primary and metastatic tumors to identify the most promising indications for future application. Methods: FAPI-PET/CTs were requested by various clinical referees according to individual clinical indication which were considered insufficiently covered by FDG-PET/CT. All...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Other Solid Tumors (Diagnosis) Source Type: research
In this study, we reviewed major human studies on the health risks of radiation exposure and showed that sex-related factors may potentially influence the long-term response to radiation exposure. Available data suggest that long-term radiosensitivity in women is higher than that in men who receive a comparable dose of radiation. The report on the biological effects of ionizing radiation (BEIR VII) published in 2006 by the National Academy of Sciences, United States emphasized that women may be at significantly greater risk of suffering and dying from radiation-induced cancer than men exposed to the same dose of radiation....
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
This study is an important step forward in highlighting C1q as a new prognostic candidate biomarker for a range of carcinomas. Methods Oncomine Database Analysis The expression levels of C1QA, C1QB, and C1QC genes in various carcinomas were analyzed using Oncomine (www.oncomine.org), a cancer microarray database and web-based data mining platform from genome-wide expression analyses (22, 23). We compared the differences in mRNA level between normal tissue and carcinoma. The mRNA expression levels in neoplastic tissues compared to the healthy tissues were obtained as the parameters of p-value 2, and gene ranking in the t...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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