Key Features Relevant to Select Antigens and TCR From the MHC-Mismatched Repertoire to Treat Cancer.

Key Features Relevant to Select Antigens and TCR From the MHC-Mismatched Repertoire to Treat Cancer. Front Immunol. 2019;10:1485 Authors: Audehm S, Glaser M, Pecoraro M, Bräunlein E, Mall S, Klar R, Effenberger M, Albers J, Bianchi HO, Peper J, Yusufi N, Busch DH, Stevanović S, Mann M, Antes I, Krackhardt AM Abstract Adoptive transfer of T cells transgenic for tumor-reactive T-cell receptors (TCR) is an attractive immunotherapeutic approach. However, clinical translation is so far limited due to challenges in the identification of suitable target antigens as well as TCRs that are concurrent safe and efficient. Definition of key characteristics relevant for effective and specific tumor rejection is essential to improve current TCR-based adoptive T-cell immunotherapies. We here characterized in-depth two TCRs derived from the human leukocyte antigen (HLA)-mismatched allogeneic repertoire targeting two different myeloperoxidase (MPO)-derived peptides presented by the same HLA-restriction element side by side comprising state of the art biochemical and cellular in vitro, in vivo, and in silico experiments. In vitro experiments reveal comparable functional avidities, off-rates, and cytotoxic activities for both TCRs. However, we observed differences especially with respect to cytokine secretion and cross-reactivity as well as in vivo activity. Biochemical and in silico analyses demonstrate different binding qualities of MPO-peptides to the HLA-complex d...
Source: Nuklearmedizin - Category: Radiology Authors: Tags: Front Immunol Source Type: research

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Condition:   Colorectal Cancer Interventions:   Drug: Chemotherapy;   Procedure: Radiofrequency ablation (RFA);   Drug: In situ immunotherapy Sponsor:   Assistance Publique - Hôpitaux de Paris Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Gastric Cancer;   Adenocarcinoma of the Esophagogastric Junction Interventions:   Drug: Nivolumab;   Drug: Ipilimumab;   Drug: Relatlimab;   Drug: Oxaliplatin;   Drug: Docetaxel;   Drug: 5-Fluorouracil;   Drug: Folic acid Sponsors:   Jan Ellermeier;   GWT-TUD GmbH Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Authors: Tsoukalas N, Theocharis MKKTMTEAFPBGKS Abstract The integration of immunotherapeutic agents in the treatment of non-small cell lung cancer (NSCLC) has revolutionized the approach of the prevalent type of lung cancer. Although PD-1 and its ligands (PD-L1 and PD-L2) are stimulating molecules of the immune-checkpoint pathway, with primary function to limit inflammatory response and autoimmunity, tumor cells have found a way to exploit these molecules by obtaining the opportunity to respond with PD-L1 expression in cytokine signals and thus to evade immune surveillance. Several immunotherapeutic agents targeti...
Source: Journal of B.U.ON. - Category: Cancer & Oncology Tags: J BUON Source Type: research
Induction of memory CD8+ T cells is important for controlling infections such as malaria and HIV/AIDS and for cancer immunotherapy. Accurate assessment of antigen-specific (Ag-specific) CD8+ T cells is critical for vaccine optimization and for defining correlates of protection. However, conditions for determining Ag-specific CD8+ T cell responses ex vivo using intracellular cytokine staining (ICS) may be variable, especially in humans with complex antigens. Here, we used an attenuated whole parasite malaria vaccine model in humans and various experimental infections in mice to show that the duration of antigenic stimulatio...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Based on the work in the Central Nervous System with discoveries of allosteric receptor-receptor interactions in homo-and heteroreceptor complexes representing a major integrative mechanism in synapses and extrasynaptic regions, it is proposed that a similar mechanism exists in the immunological synapses. We discuss a putative additional molecular mechanism for the ability of the inhibitory T cell signaling proteins CTLA-4 and PD-1 and the adenosine A2AR to diminish T cell activation leading to enhancement of cancer development. We suggest that in the same immunological synapse involving T cells and antigen presenting cell...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
The management of stage IIIA (N2) non-small cell lung cancer (NSCLC) is an area of thoracic oncology in constant controversy and evolution. Historically, the high rate of distant metastatic disease and poor long-term survival made maximal loco-regional disease control obsolete. The role of surgical therapy, which offers the best chance for durable loco-regional disease control in stage IIIA lung cancer, has been debated. This is mainly because of the lack of level I evidence demonstrating benefit of surgery over chemoradiation alone.
Source: Seminars in Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: THORACIC – Editorial Commentary Source Type: research
Conclusions: These findings demonstrated that TILs are potential survival predictors in HCC and different kinds of TILs are observed according to the virus type. Therefore, further investigations are warranted to elucidate the role of TILs in HCC, which may improve immunotherapy outcomes.
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
Immunotherapy using checkpoint-blocking antibodies against PD-1 has produced impressive results in a wide range of cancers. However, the response remains heterogeneous among patients. We used noninvasive immuno-positron emission tomography (PET), using 89Zr-labeled PEGylated single-domain antibody fragments (nanobodies or VHHs), to explore the dynamics and distribution of intratumoral CD8+ T cells...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus Source Type: research
This article deciphers emerging research trends to ameliorate four challenges unaddressed by the iRANO criteria: (1) patient selection, (2) identification of immune-related phenomena other than pseudoprogression (i.e., hyperprogression, the abscopal effect, immune-related adv erse events), (3) response assessment in combination therapies including ICM, and (4) alternatives to MRI. To this end, our article provides a structured approach for standardized selection and reporting of imaging modalities to enable the use of precision medicine by deciphering the characteristics of the tumor and its immune environment. Emerging pr...
Source: EJNMMI Research - Category: Radiology Source Type: research
Nano LettersDOI: 10.1021/acs.nanolett.9b02923
Source: Nano Letters - Category: Nanotechnology Authors: Source Type: research
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