Identification of cell surface proteins as potential immunotherapy targets in twelve pediatric cancers
Technological advances now allow us to rapidly produce CARs and other antibody-derived therapeutics targeting cell surface receptors. To maximize the potential of these new technologies, relevant extracellular targets must be identified. The Pediatric Oncology Branch of the NCI curates a freely ac...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2012.00194/full |
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| author | Rimas J Orentas James J Yang Xinyu eWen Jun S. Wei Crystal L Mackall Javed eKhan |
| author_facet | Rimas J Orentas James J Yang Xinyu eWen Jun S. Wei Crystal L Mackall Javed eKhan |
| author_sort | Rimas J Orentas |
| collection | DOAJ |
| description | Technological advances now allow us to rapidly produce CARs and other antibody-derived therapeutics targeting cell surface receptors. To maximize the potential of these new technologies, relevant extracellular targets must be identified. The Pediatric Oncology Branch of the NCI curates a freely accessible database of gene expression data for both pediatric cancers and normal tissues, through which we have defined discrete sets of over-expressed transcripts in twelve pediatric cancer subtypes as compared to normal tissues. We coupled gene expression profiles to current annotation databases (i.e., Affymetrix, Gene Ontology, Entrez Gene), in order to categorize transcripts by their subcellular location. In this manner we generated a list of potential immune targets expressed on the cell surface, ranked by their difference from normal tissue. Global differences from normal between each of the pediatric tumor types studied varied, indicating that some malignancies expressed transcript sets that were more highly diverged from normal tissues than others. The validity of our approach is seen by our findings for pre-B cell ALL, where targets currently in clinical trials were top-ranked hits (CD19, CD22). For some cancers, reagents already in development could potentially be applied to a new disease class, as exemplified by CD30 expression on sarcomas. Moreover, several potential new targets shared among several pediatric solid tumors are herein identified, such as MCAM (MUC18), MTDH (metadherin), and GPC2 (glypican-2). These targets have been identified at the mRNA level and are yet to be validated at the protein level. The safety of targeting these antigens has yet to be demonstrated and therefore the identified transcripts should be considered preliminary candidates for new CAR and therapeutic antibody targets. Prospective candidate targets will be evaluated by proteomic analysis including Westerns and immunohistochemistry of normal and tumor tissues. |
| first_indexed | 2024-12-22T08:29:18Z |
| format | Article |
| id | doaj.art-f4780f8e34dd424a96ef8606df1e1ed0 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-22T08:29:18Z |
| publishDate | 2012-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-f4780f8e34dd424a96ef8606df1e1ed02022-12-21T18:32:33ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2012-12-01210.3389/fonc.2012.0019437328Identification of cell surface proteins as potential immunotherapy targets in twelve pediatric cancersRimas J Orentas0James J Yang1Xinyu eWen2Jun S. Wei3Crystal L Mackall4Javed eKhan5National Institutes of Health, National Cancer InstituteNational Institutes of Health, National Cancer InstituteNational Institutes of Health, National Cancer InstituteNational Institutes of Health, National Cancer InstituteNational Institutes of Health, National Cancer InstituteNational Institutes of Health, National Cancer InstituteTechnological advances now allow us to rapidly produce CARs and other antibody-derived therapeutics targeting cell surface receptors. To maximize the potential of these new technologies, relevant extracellular targets must be identified. The Pediatric Oncology Branch of the NCI curates a freely accessible database of gene expression data for both pediatric cancers and normal tissues, through which we have defined discrete sets of over-expressed transcripts in twelve pediatric cancer subtypes as compared to normal tissues. We coupled gene expression profiles to current annotation databases (i.e., Affymetrix, Gene Ontology, Entrez Gene), in order to categorize transcripts by their subcellular location. In this manner we generated a list of potential immune targets expressed on the cell surface, ranked by their difference from normal tissue. Global differences from normal between each of the pediatric tumor types studied varied, indicating that some malignancies expressed transcript sets that were more highly diverged from normal tissues than others. The validity of our approach is seen by our findings for pre-B cell ALL, where targets currently in clinical trials were top-ranked hits (CD19, CD22). For some cancers, reagents already in development could potentially be applied to a new disease class, as exemplified by CD30 expression on sarcomas. Moreover, several potential new targets shared among several pediatric solid tumors are herein identified, such as MCAM (MUC18), MTDH (metadherin), and GPC2 (glypican-2). These targets have been identified at the mRNA level and are yet to be validated at the protein level. The safety of targeting these antigens has yet to be demonstrated and therefore the identified transcripts should be considered preliminary candidates for new CAR and therapeutic antibody targets. Prospective candidate targets will be evaluated by proteomic analysis including Westerns and immunohistochemistry of normal and tumor tissues.http://journal.frontiersin.org/Journal/10.3389/fonc.2012.00194/fullGene Expression ProfilingGlioblastomaHepatoblastomaNeuroblastomaOsteosarcomaRhabdomyosarcoma |
| spellingShingle | Rimas J Orentas James J Yang Xinyu eWen Jun S. Wei Crystal L Mackall Javed eKhan Identification of cell surface proteins as potential immunotherapy targets in twelve pediatric cancers Frontiers in Oncology Gene Expression Profiling Glioblastoma Hepatoblastoma Neuroblastoma Osteosarcoma Rhabdomyosarcoma |
| title | Identification of cell surface proteins as potential immunotherapy targets in twelve pediatric cancers |
| title_full | Identification of cell surface proteins as potential immunotherapy targets in twelve pediatric cancers |
| title_fullStr | Identification of cell surface proteins as potential immunotherapy targets in twelve pediatric cancers |
| title_full_unstemmed | Identification of cell surface proteins as potential immunotherapy targets in twelve pediatric cancers |
| title_short | Identification of cell surface proteins as potential immunotherapy targets in twelve pediatric cancers |
| title_sort | identification of cell surface proteins as potential immunotherapy targets in twelve pediatric cancers |
| topic | Gene Expression Profiling Glioblastoma Hepatoblastoma Neuroblastoma Osteosarcoma Rhabdomyosarcoma |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2012.00194/full |
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