RAV 12 / MacroGenics - LARVOL DELTA

Comprehensive analysis of TCR repertoire in COVID-19 using single cell sequencing. (PubMed, Genomics) - "When considering the VJ combination of α and β chains at the same time, the combination with the highest frequency on COVID-19 was TRAV12-2-J27-TRBV7-9-J2-3. Besides, preferential usage of V and J gene segments was also observed in samples infected by different viruses. Our study provides novel insights on TCR in COVID-19, which contribute to our understanding of the immune response induced by SARS-CoV-2."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Analysis of the paired TCR- and -V(D)J full-length chains of single-cell sequence from human nave and antigen-experienced T cells (AACR 2018) - "...Finally, we obtained the paired, full-length V(D)J TCR from melanoma antigen Melan A epitope 27-35 that was TRAV(12-2)J(47), TRBV(7-6)J(2-1), and the TCR from antigen EBV LMP2-FLY that was TRAV(26-1)J(7), TRBV(27)J(2-1). These results suggest that the method provides accurate identification of the paired, V(D)J rearrangements for each individual human nave and antigen-experienced T cells. The information could be used in the construction of an engineered T-cell receptor for cancer immunotherapy and infectious diseases."

Melanoma

A linear-amplification VDJ-seq technique for quantification of immunoglobulin and T cell receptor diversity. (PubMed, Genome) - "The Jκ genes were detected in 95.86% of clean reads with more than half containing Vκ gene, indicating high specificity of capturing and amplification. We also applied it for quantifying of the Jα usage of Trav12 family of Tcra gene."

Journal

[VIRTUAL] THE FIRST FUNCTIONAL HLA-A*01:01-RESTRICTED EBV-LMP2-SPECIFIC T-CELL RECEPTORS FOR TCR GENE THERAPY OF PATIENTS WITH EBV-ASSOCIATED TYPE II/III MALIGNANCIES (EBMT 2020) - "Additionally, for TCRalpha-chain expression these populations used either TRAV12 or TRAV30... In conclusion, we isolated and validated the first functional HLA-A*01:01-restricted EBV-LMP2-specific T-cell populations and TCRs, which can be used for adoptive transfer or retro/lentiviral TCR gene therapy to treat EBV-associated type II/III lymphomas, EBV+ malignancies of epithelial origin and PTLDs."

Clinical • IO Biomarker • Burkitt Lymphoma • Epstein-Barr Virus Infection • Gastric Cancer • Gastrointestinal Cancer • Gene Therapies • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Lymphoma • Nasopharyngeal Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Transplantation • CD8

[VIRTUAL] THE FIRST FUNCTIONAL HLA-A*01:01-RESTRICTED EBV-LMP2-SPECIFIC T-CELL RECEPTORS FOR TCR GENE THERAPY OF PATIENTS WITH EBV-ASSOCIATED TYPE II/III MALIGNANCIES (EBMT 2020) - "Additionally, for TCRalpha-chain expression these populations used either TRAV12 or TRAV30... In conclusion, we isolated and validated the first functional HLA-A*01:01-restricted EBV-LMP2-specific T-cell populations and TCRs, which can be used for adoptive transfer or retro/lentiviral TCR gene therapy to treat EBV-associated type II/III lymphomas, EBV+ malignancies of epithelial origin and PTLDs."

Clinical • IO Biomarker • Burkitt Lymphoma • Epstein-Barr Virus Infection • Gastric Cancer • Gastrointestinal Cancer • Gene Therapies • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Lymphoma • Nasopharyngeal Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Transplantation • CD8

[VIRTUAL] THE FIRST FUNCTIONAL HLA-A*01:01-RESTRICTED EBV-LMP2-SPECIFIC T-CELL RECEPTORS FOR TCR GENE THERAPY OF PATIENTS WITH EBV-ASSOCIATED TYPE II/III MALIGNANCIES (EBMT 2020) - "Additionally, for TCRalpha-chain expression these populations used either TRAV12 or TRAV30... In conclusion, we isolated and validated the first functional HLA-A*01:01-restricted EBV-LMP2-specific T-cell populations and TCRs, which can be used for adoptive transfer or retro/lentiviral TCR gene therapy to treat EBV-associated type II/III lymphomas, EBV+ malignancies of epithelial origin and PTLDs."

Clinical • IO Biomarker • Burkitt Lymphoma • Epstein-Barr Virus Infection • Gastric Cancer • Gastrointestinal Cancer • Gene Therapies • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Lymphoma • Nasopharyngeal Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Transplantation • CD8

[VIRTUAL] THE FIRST FUNCTIONAL HLA-A*01:01-RESTRICTED EBV-LMP2-SPECIFIC T-CELL RECEPTORS FOR TCR GENE THERAPY OF PATIENTS WITH EBV-ASSOCIATED TYPE II/III MALIGNANCIES (EBMT 2020) - "Additionally, for TCRalpha-chain expression these populations used either TRAV12 or TRAV30... In conclusion, we isolated and validated the first functional HLA-A*01:01-restricted EBV-LMP2-specific T-cell populations and TCRs, which can be used for adoptive transfer or retro/lentiviral TCR gene therapy to treat EBV-associated type II/III lymphomas, EBV+ malignancies of epithelial origin and PTLDs."

Clinical • IO Biomarker • Burkitt Lymphoma • Epstein-Barr Virus Infection • Gastric Cancer • Gastrointestinal Cancer • Gene Therapies • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Lymphoma • Nasopharyngeal Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD8

Atypical TRAV1-2- T cell receptor recognition of the antigen-presenting molecule MR1. (PubMed, J Biol Chem) - "Here, we describe how a TRAV12-2+ TCR (termed D462-E4) recognises an MR1-antigen complex. We report the crystal structures of the unliganded D462-E4 TCR and its complex with MR1 presenting the riboflavin-based antigen, 5-OP-RU...The D462-E4 TCR footprint on MR1 contrasted that of the TRAV1-2+ and TRAV36+ TCRs docking topologies on MR1. Accordingly, diverse MR1-restricted T cell repertoire reveals differential docking modalities on MR1, thus providing greater scope for differing antigen specificities."

Journal • Immunology

Genes of the RAV family control heading date and carpel development in rice. (PubMed, Plant Physiol) - "Furthermore, OsRAV11 and OsRAV12 may have ac-quired a novel function in the differentiation of the carpel and the control of seed size, acting downstream of floral homeotic factors. Alternatively, this function may have been lost in Arabidopsis. Our data reveal conservation of RAV gene function in the regulation of flowering time in monocotyledonous and dicotyledonous plants, but also unveil roles in the development of rice gynoecium."

Journal

Unpredicted phenotypes of two mutants of the TcR DMF5. (PubMed) - "In addition, the soluble TcR form of this mutant bound target cells less efficiently. From this we concluded that kinetic parameters do not always predict the superior functionality of mutant TcRs."

Journal • Biosimilar • Melanoma • Oncology

Identification of T cell epitopes in sarcoidosis (IMMUNOLOGY 2020) - "We hypothesize that in these HLA-DR3+ LS patients, TRAV12-1/TRBV2 CD4+ T cell clones accumulate and expand in the lung in response to unknown etiologic antigens...Peptides that stimulate LS-associated TCRs have not been discovered until now, making this a major novel achievement in the field. Identification of an etiologic antigen in LS will narrow our search of the stimuli driving sarcoidosis in the US."

IO Biomarker

Genomic profiling of intestinal T-cell receptor repertoires in inflammatory bowel disease. (PubMed, Genes Immun) - "Our approach further identified the increased usage of TRAV12-3 (false discovery rate, FDR < 5%), which biases its choices of J genes towards the reduction of TRAJ37 and TRAJ43 usage (FDR < 20%) in the inflamed intestine. Our genomic profiling suggests that this selective bias of V and J gene usage may lead to a loss of diversity in the intestinal TCR repertoires and result in mucosal inflammation in IBD."

Journal

The First Functional HLA-a*01:01-Restricted EBV-LMP2-Specific T-Cell Receptors for TCR Gene Therapy of Patients with EBV-Associated Type II/III Malignancies (ASH 2019) - "Additionally, for TCRalpha-chain expression these populations used either TRAV12 or TRAV30...Finally, recognition of HLA-A*01:01+ EBV-LCLs demonstrated the potential of these EBV-LMP2-ESE-specific TCRs to recognize naturally occurring endogenous LMP2. In conclusion, we isolated and validated the first functional HLA-A*01:01-restricted EBV-LMP2-specific T-cell populations and TCRs, which can be used for adoptive transfer or retro/lentiviral TCR gene therapy to treat EBV-associated type II/III lymphomas, EBV+ malignancies of epithelial origin and PTLDs."

Clinical • IO Biomarker • CD8

"Follow today's #NHSfalls summit @antigrav123 @NICEComms @falls_network @thecsp @BritOrthopaedic @RoyalOsteoPro @FallsKent @LPTFALLS @BWFallsTherapy @HealthPhysio @AgeActAlliance @Ageing_Better @BoneJointJ @RCP_FFFAP @KingsCollegeLon @JointRegistry @BritishHipSoc @GeriSoc" (@HCUK_Clare)

"2. https://t.co/1kuwRav12Z" (@T_Allen1998)

CD4+ T cell antigen discovery in sarcoidosis (AAI 2019) - "...We hypothesize that in HLA-DR3+ LS patients, TRAV12-1 CD4+ T cell clones accumulate and expand in the lung in response to unknown antigens...We used a biometrical analysis to obtain candidate etiologic peptides derived from human, viral, pollen, and mycobacterial protein databases and have identified several exogenous peptides that stimulate TCRs derived from the BAL of patients with active LS. Once etiologic antigens are validated, we will synthesize HLA-DR3-peptide tetramers to allow for more sophisticated approaches in the diagnosis and prognosis of this disease"

IO Biomarker

"NBA roundup: Westbrook posts eighth straight triple-double https://t.co/rYCIRAvH12" (@Reuters)