A Bispecific Antibody to Link a TRAIL-Based Antitumor Approach to Immunotherapy

T-cell-based immunotherapy strategies have profoundly improved the clinical management of several solid tumors and hematological malignancies. A recently developed and promising immunotherapy approach is to redirect polyclonal MHC-unrestricted T lymphocytes toward cancer cells by bispecific antibodies (bsAbs) that engage the CD3 complex and a tumor-associated antigen (TAA). The TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) is an attractive immunotherapy target, frequently expressed by neoplastic cells, that we decided to exploit as a TAA. We found that a TRAIL-R2xCD3 bsAb efficiently activates T cells and specifically redirect their cytotoxicity against cancer cells of different origins in vitro, thereby demonstrating its potential as a pan-carcinoma reagent. Moreover, to mimic in vivo conditions, we assessed its ability to retarget T-cell activity in an ex vivo model of ovarian cancer patients' ascitic fluids containing both effector and target cells—albeit with a suboptimal effector-to-target ratio—with remarkable results.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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sen K Abstract Introduction: The aim of the present study was to investigate the prognostic impact of intratumoral cytotoxic T cells, Natural Killer (NK) cells, neutrophils and PD-L1 expression in patients with epithelial ovarian cancer.Methods: All patients diagnosed with high-grade serous carcinoma (HGSC) in Denmark in 2005 were included in the study. Immunohistochemical staining for PD-L1, CD8, CD66b and CD57 was performed on tumor tissue from 283 patients. Cell densities were analyzed using a digital image analysis method. The primary endpoint was overall survival (OS).Results: The median OS for HGSC patients ...
Source: Acta Oncologica - Category: Cancer & Oncology Authors: Tags: Acta Oncol Source Type: research
Publication date: Available online 3 January 2020Source: Seminars in Cancer BiologyAuthor(s): Kelly Olino, Tristen Park, Ntia AhujaAbstractAdvances in immunotherapy, most notably antibodies targeting the inhibitory immune receptors cytotoxic T-lymphocyte associated protein 4 (CTLA-4/CD152), programmed death protein 1 (PD-1/CD279) and programmed death-ligand 1 (PD-L1/B7H1/CD274) have become effective standard therapies in advanced malignancies including melanoma,1–4 merkel cell carcinoma5, urological cancers6–8, non-small cell lung cancer9–11, mis-match repair (MMR) deficient tumors12, and Hodgkin lymphoma...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Authors: Flores I, Hevia D, Tittarelli A, Soto D, Rojas-Sepúlveda D, Pereda C, Tempio F, Fuentes C, Falcón-Beas C, Gatica J, Falcón-Beas F, Galindo M, Salazar-Onfray F, González FE, López MN Abstract Ovarian epithelial carcinoma (OEC) is the most frequent ovarian tumor, characterized by a high mortality in advanced stages where conventional therapies are not effective. Based on the role of the immune system in the progression of this disease, immunotherapy using checkpoint blockade has been considered as a therapeutic alternative. Nevertheless, its results do not match up to the p...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
This study aimed to reveal the role of TEX19 in ovarian cancer (OC) and searched for potential candidate epitope peptides of TEX19 to facilitate clinical application.Main methodsTEX19 levels were evaluated by immunohistochemistry (IHC) in 98 human ovarian tissue samples. The correlation of TEX19 levels with patients' clinicopathological features was assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were utilized to detect TEX19 levels in ovarian cell lines and TEX19-deficient cells. The level of TEX19 in OVCAR-3 and A2780 was knocked down by small interfering RNA (siRNA), an...
Source: Life Sciences - Category: Biology Source Type: research
ConclusionsBTLA detected in cancerous tissues can predict poor outcome of EOC patients. Inhibition of BTLA combined with chemotherapy can elevate immune activation and generate potent anti-tumor effects. Thus, the combination of chemotherapy and anti-BTLA antibody may hold potential clinical application for the treatment of EOC patients.Trial registrationThe Trial Registration Number wasNCT00854399.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
ConclusionsOur data indicate that CALR levels in primary and metastatic HGSC samples have robust prognostic value linked to the activation of clinically-relevant innate and adaptive anticancer immune responses.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
CONCLUSION: In the last decade, promising biomarkers have been validated and lead to new therapeutic strategies with PARP inhibitors, immunotherapy and anti-angiogenic agents. Biomarkers such as BRCA, homologus recombination defect (HRD), immuno-markers (CD8, PD-1, PDL-1), KRAS and PR, are now used in clinical trials. Other: Assessment of genetic variants will soon represent the standard-of-care in gynecological cancers, not only to diagnose the disease but also to assist the prediction of clinical behavior of tumors and support personalized medicine to match patients with appropriate targeted therapies, improving treatmen...
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Targets Source Type: research
This report describes a patient whose presenting complaints were “Physical examination showed that the pancreas was occupied for one month.” He initially was diagnosed with stage IV PC based on conventional imaging and pathologic assessment. He had a known germline BRCA 2 mutation, which exhibited a good response to PARP inhibitor therapy. Diagnosis: Through the biopsy histopathological examination, imaging examination, and genetic testing, the patient was diagnosed as metastatic PC with BRCA2 mutation. Interventions: He received gemcitabine and albumin-bound paclitaxel chemotherapy from March 15, 2017 to...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
In this study, HER2 and MUC1-based peptides were synthesized and preclinically evaluated in an effort to develop peptide-based SPECT radiopharmaceuticals derived from tumor-associated antigens for the detection of breast cancer. Our findings demonstrate that the tumor antigen peptides radiolabeled efficiently with 99mTc and showed high metabolic stability in human plasma in vitro. The data from breast tumor cell binding confirmed the high affinity (in low nanomolar range) towards respective breast cancer cell lines. In healthy mice, 99mTc-labeled peptides displayed favorable pharmacokinetics, with high excretion by the ren...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Conditions:   Fallopian Tube Carcinosarcoma;   Fallopian Tube Clear Cell Adenocarcinoma;   Fallopian Tube Transitional Cell Carcinoma;   Fallopian Tube Undifferentiated Carcinoma;   Germline BRCA1 Gene Mutation;   Germline BRCA2 Gene Mutation;   High Grade Fallopian Tube Serous A denocarcinoma;   High Grade Ovarian Serous Adenocarcinoma;   Ovarian Clear Cell Tumor;   Ovarian Seromucinous Carcinoma;   Ovaria...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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