Ifabotuzumab, which targets the Eph type-A receptor 3 (EphA3
), is being explored as a potential treatment for a range of solid tumors, as well as a backbone for a novel CAR-T construct, and a bispecific antibody platform.
Gene name Gene Conserved 8-mer 7-mer symbol sites Chemokine Z (C-X-C motif) CXC 12 1 1 ligand 12 NOTCH-regulated ankyrin NRARP 1 1 repeat protein Astrotactin-1 ASTN1 1 1 Nasal embryonic LHRH NELF 1 1 factor K(Lysine) acetyl KAT6B 1 1 transferase 6B Protein kinase C, alpha PRKCA 1 1 EF-hand domain family, EFHD2 1 1 member D2 Mitogen-activated protein MAP2K4 1 1 kinase kinase 4 Zinc finger protein 219 ZNF219 1 1 Ring finger protein 165 RNF165 1 1 Protocadherin 7 PCDH7 1 1 EPH receptor A3 EPHA3
1 1 Insulin receptor IRS1 1 1 substrate 1 POU class 2 homeobox 1 POU2F1 1 1
Los genes involucrados se asocian a diferentes etapas del proceso de carcinogenesis, como la regulacion del ciclo celular y la apoptosis (p15, p16, Rb1, p27, p73), la reparacion del ADN (MgMTdApK), la migracion y metastasis tumoral (E-cadherin, RAE[beta]), los factores de crecimiento (ER, EphA3
), la diferenciacion celular y la respuesta inmune (C/EBPs), (SOCS-1), entre otros.
In our prediction list, five genes can be classified in such subfamily: EPHA3
, EPHA4, EPHA5, EPHA7, and EPHB2.
The protein, (http://www.ncbi.nlm.nih.gov/pubmed/23410976) EphA3
, was discovered more than 20 years ago by QIMR Berghofer Medical Research Institute's professor, Andrew Boyd.
Symbol Entrez gene name WNT16 Wingless-type MMTV integration site family, member 16 PLCD4 Phospholipase C, delta 4 ADAM29 ADAM metallopeptidase domain 29 MMP8 Matrix metallopeptidase 8 (neutrophil collagenase) EPHA6 EPH receptor A6 PAK7 p21 protein (Cdc42/Rac)-activated kinase 7 EPHA7 EPH receptor A7 EPHA3
EPH receptor A3 SEMA6D Serna domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6D ADAM30 ADAM metallopeptidase domain 30 UNC5D Unc-5 homolog D (C.
Cruz-Orengo et al., "Upregulation of EphA3
receptor after spinal cord injury," Journal of Neurotrauma, vol.
KaloBios Pharmaceuticals, a biopharmaceutical company, has received a notice of allowance for a composition of matter patent covering certain antibodies targeting EphA3
, including KaloBios' experimental anti-cancer monoclonal antibody (mAb), KB004, with the US Patent and Trademark Office.
Among neural-derived cells, integrated mRNA-miRNA functional analyses of mature neurons (MNs), neural progenitor cells (NPCs), and neuroblastoma cells (NBCs) revealed that several very highly expressed genes (e.g., Robo1, Nrp1, Epha3
, Unc5c, Dcc, Pak3, and Limk4) and a few underexpressed miRNAs (e.g., miR-152, miR-146b, and miR-339-5p) in MNs are associated with one important cellular process-axon guidance; some very highly expressed mitogenic pathway genes (e.g., Map2k1, Igf1r, Rara, and Runx1) and underexpressed miRNAs (e.g., miR-370, miR-9, and miR-672) in NBCs are associated with cancer pathways .
These mutations were associated with 12 core signaling pathways.7 Based on the frequency of genetically affected genes in pancreatic cancers, a genetic "topographic map" of the pancreatic cancers can be generated in which the most frequent mutations are represented as 4 "mountains" (high-frequency driver genes) involving KRAS2, CDKN2A/p16, SMAD4/DPC4, and TP53, with numerous "hills" (low-frequency driver genes) involving SMARC4A, CDH1, EPHA3
, FBXW7, EGFR, IDH1, and NF1.
It is targeted towards EphA3
expressing hematologic malignancies, which are believed to account for about 50 percent of acute leukaemias as well as a number of other human cancers, including a significant proportion of malignant melanomas, brain tumours and lung cancers.
It's still early days but there are reports that EphA3
, A4, A7 and B3 all reappear following injury.