Last update 01 Nov 2024

HLA class II antigen x TERT

Last update 01 Nov 2024

Basic Info

Related Targets

HLA class II antigenTERT

Drugs associated with HLA class II antigen x TERT

ZI-H04

Target

HLA class II antigen x TERT

Mechanism

HLA class II antigen inhibitors [+1]

Active Org.

Zelluna Immunotherapy ASStartup

Originator Org.

Zelluna Immunotherapy ASStartup

Active Indication

Solid tumor

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with HLA class II antigen x TERT

100 Translational Medicine associated with HLA class II antigen x TERT

0 Patents (Medical) associated with HLA class II antigen x TERT

Literatures (Medical) associated with HLA class II antigen x TERT

01 Jul 2024·Hepatology

Genome-wide association study identifies high-impact susceptibility loci for HCC in North America

Article

Author: Long, Erping ; Schmidt, Mikayla A. ; Gu, Jian ; Rashid, Asif ; Goss, John A. ; Singal, Amit G. ; Permuth, Jennifer B. ; Liu, Geoffrey ; Beretta, Laura ; Byun, Jinyoung ; Lee, Sunyoung S. ; Yuan, Jian-Min ; Hassan, Manal M. ; Li, Yanan ; Roberts, Lewis R. ; Kono, Yuko ; Klein, Alison P. ; El-Serag, Hashem ; White, Donna L. ; Zhang, Karen ; Cigarroa, Francisco G. ; Shah, Dimpy P. ; Hatia, Rikita I. ; Wolff, Robert A. ; Santella, Regina M. ; Marrero, Jorge A. ; Li, Donghui ; Cleary, Sean P. ; Parikh, Neehar D. ; Huff, Chad ; Kim, Richard ; Khaderi, Saira A. ; Hwang, Lu-Yu ; Amos, Christopher I. ; Lok, Anna S. ; Han, Younghun ; Amin, Hesham M. ; Antwi, Samuel O. ; Choi, Jiyeon ; Bucur, Roxana ; Patt, Yehuda ; Bracci, Paige ; Hawk, Ernest ; Sun, Ryan ; Wu, Hui-Chen ; Kelley, Robin Kate ; Chang, Ping ; Nguyen, Mindie H. ; Kaseb, Ahmed O. ; Jalal, Prasun K. ; Shah, Pankil K. ; Chun, Yun Shin ; Ghobrial, R. Mark

Background and Aims:Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP).Approach and Results:We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP, rs9842969, (0.51, [0.40–0.65]); 5p15.33, TERT, rs2242652, (0.70, (0.62–0.79]); 19q13.11, TM6SF2, rs58542926, (1.49, [1.29–1.72]); 19p13.11 MAU2, rs58489806, (1.53, (1.33–1.75]); and 22q13.31, PNPLA3, rs738409, (1.66, [1.51–1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74–0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC.Conclusions:Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

01 Nov 2020·Brain PathologyQ1 · MEDICINE

Epithelioid glioblastoma with microglia features: potential for novel therapy

Q1 · MEDICINE

Article

Author: Nakagomi, Nami ; Yoshimura, Shinichi ; Hirota, Seiichi ; Nakagomi, Takayuki ; Sakamoto, Daisuke ; Hirose, Takanori ; Murase, Makiko ; Takagi, Toshinori

AbstractEpithelioid glioblastoma (E‐GBM) was recently designated as a subtype of glioblastoma (GBM) by the World Health Organization (2016). E‐GBM is an aggressive and rare variant of GBM that primarily occurs in children and young adults. Although most characterized cases of E‐GBM harbor a mutation of the BRAF gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600 (BRAF‐V600E), in addition to telomerase reverse transcriptase promoter mutations and homozygous CDKN2A/B deletions, the origins and cellular nature of E‐GBM remain uncertain. Here, we present a case of E‐GBM that exhibits antigenic and functional traits suggestive of microglia. Although no epithelial [e.g., CKAE1/3, epithelial membrane antigen (EMA)] or glial (e.g., GFAP, Olig2) markers were detected by immunohistochemical staining, the microglial markers CD68 and Iba1 were readily apparent. Furthermore, isolated E‐GBM‐derived tumor cells expressed microglial/macrophage‐related genes including cytokines, chemokines, MHC class II antigens, lysozyme and the critical functional receptor, CSF‐1R. Isolated E‐GBM‐derived tumor cells were also capable of phagocytosis and cytokine production. Treating E‐GBM‐derived tumor cells with the BRAF‐V600E inhibitor, PLX4032 (vemurafenib), resulted in a dose‐dependent reduction in cell viability that was amplified by addition of the CSF‐1R inhibitor, BLZ945. The present case provides insight into the cellular nature of E‐GBM and introduces several possibilities for effective targeted therapy for these patients.

01 Dec 2019·International Journal of Cancer

CD4 T cells target colorectal cancer antigens upregulated by oxaliplatin

Article

Author: Royer, Bernard ; Adotévi, Olivier ; Vauchy, Charline ; Loyon, Romain ; Mouget, Virginie ; Laheurte, Caroline ; Turco, Célia ; Godet, Yann ; Jary, Marine ; Queiroz, Lise ; Mercier‐Letondal, Patricia ; Boidot, Romain ; Galaine, Jeanne ; Borg, Christophe ; Lakkis, Zaher

Immune checkpoint blockade has proven its efficacy in hypermutated subtypes of metastatic colorectal cancers (mCRC). Immunogenic potential can also be observed with conventional chemotherapies, but this property has never been explored thoroughly in CRC patients. The CRC therapeutic arsenal includes oxaliplatin, a well‐characterized platinum drug already described as immunogenic. Here, we investigated the impact of the oxaliplatin‐based treatment on mCRC immunopeptidome. We demonstrated that oxaliplatin‐resistant CRC cell lines overexpressed telomerase reverse transcriptase (TERT), colorectal‐associated‐tumor antigen‐1 (COA‐1) and mesothelin tumor‐associated antigens. We identified new HLA class‐II‐restricted and promiscuous peptides derived from COA‐1 and mesothelin. The two naturally processed peptides COA‐1331‐345 and Meso366‐380 appear to be the most immunogenic in mCRC patients. A prospective cohort of 162 mCRC patients enabled us to explore the impact of oxaliplatin exposure on the antitumor‐specific immune response. Interestingly, chemotherapy‐naive mCRC patients present high immune CD4 T‐cell responses directed against TERT, COA‐1 and mesothelin‐derived peptides. These antitumor T‐cell responses were maintained after 3 months of oxaliplatin‐based treatment. Altogether, these findings highlight the interest of immunostimulatory agents to improve the management of chemoresistant mCRC patients. Finally, the high frequency of immune responses targeting the new immunogenic peptides derived from COA‐1 and mesothelin support their use in immunomonitoring strategies.

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