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Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy.

ABSTRACT: We evaluated and compared tumor antigen precursor protein (TAPP) profiles in adult and pediatric brain tumors of 31 genes related to tumor associated antigens (TAA) for possible use in immunotherapy. Antigens were selected based on their potential to stimulate T cell responses against tumors of neuroectodermal origin.Thirty-seven brain tumor specimens from 11 adult and 26 pediatric patients were analyzed by quantitative real-time PCR for the relative expression of 31 TAPP mRNAs. The age range of adults (4F:7M) was 27-77 years (median 51.5 +/- 14.5 years) and for pediatrics (12F:14M) was 0.9-19 years (median 8.3 +/- 5.5 years). Histological diagnoses consisted of 16 glioblastomas, 4 low grade astrocytomas, 10 juvenile pilocytic astrocytomas, and 7 ependymomas.The adult gliomas expressed 94% (29 of 31) of the TAPP mRNAs evaluated compared with pediatric brain tumors that expressed 55-74% of the TAPP mRNAs, dependent on tumor histological subtype. Four types of TAPP expression patterns were observed: (1) equal expression among adult and pediatric cases, (2) greater expression in adult than pediatric cases, (3) expression restricted to adult GBM and (4) a random distribution. The pediatric brain tumors lacked expression of some genes associated with engendering tumor survival, such as hTert and Survivin.The potential TAA targets identified from the TAPP profiles of 31 genes associated with adult and pediatric brain tumors may help investigators select specific target antigens for developing dendritic cell- or peptide-based vaccines or T cell-based immunotherapeutic approaches against brain tumors.

SUBMITTER: Zhang JG

PROVIDER: S-EPMC4005736 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy.

Zhang Jian Gang JG Kruse Carol A CA Driggers Lara L Hoa Neil N Wisoff Jeffrey J Allen Jeffrey C JC Zagzag David D Newcomb Elizabeth W EW Jadus Martin R MR

Journal of neuro-oncology 20080208 1

<h4>Objectives</h4>We evaluated and compared tumor antigen precursor protein (TAPP) profiles in adult and pediatric brain tumors of 31 genes related to tumor associated antigens (TAA) for possible use in immunotherapy. Antigens were selected based on their potential to stimulate T cell responses against tumors of neuroectodermal origin.<h4>Methods</h4>Thirty-seven brain tumor specimens from 11 adult and 26 pediatric patients were analyzed by quantitative real-time PCR for the relative expression ...[more]

PMID: 18259692

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Project description:Background and objectiveThe goal of this narrative review is to report and summarize the completed pediatric immunotherapy clinical trials for primary CNS tumors. Pediatric central nervous system (CNS) tumors are the most common cause of pediatric solid cancer in children aged 0 to 14 years and the leading cause of cancer mortality. Survival rates for some pediatric brain tumors have improved, however, there remains a large portion of pediatric brain tumors with poor survival outcomes despite advances in treatment. Cancer immunotherapy is a growing field that has shown promise in the treatment of pediatric brain tumors that have historically shown a poor response to treatment. This narrative review provides a summary and discussion of the published literature focused on treating pediatric brain tumors with immunotherapy.MethodsMEDLINE via PubMed, Embase and Scopus via Elsevier were searched. The search utilized a combination of keywords and subject headings to include pediatrics, brain tumors, and immunotherapies. Manuscripts included in the analysis included completed clinical studies using any immunotherapy intervention with a patient population that consisted of at least half pediatric patients (<18 years) with primary CNS tumors. Conference abstracts were excluded as well as studies that did not include completed safety or primary outcome results.Key content and findingsSearch results returned 1,494 articles. Screening titles and abstracts resulted in 180 articles for full text review. Of the 180 articles, 18 were included for analysis. Another two articles were ultimately included after review of references and inclusion of newly published articles, for a total of 20 included articles. Immunotherapies included dendritic cell vaccines, oncolytic virotherapy/viral immunotherapy, chimeric antigen receptor (CAR) T-cell therapy, peptide vaccines, immunomodulatory agents, and others.ConclusionsIn this review, 20 published articles were highlighted which use immunotherapy in the treatment of primary pediatric brain tumors. To date, most of the studies published utilizing immunotherapy were phase I and pilot studies focused primarily on establishing safety and maximum dose-tolerance and toxicity while monitoring survival endpoints. With established efficacy and toxicity profiles, future trials may progress to further understanding the overall survival and quality of life benefits to pediatric patients with primary brain tumors.

Dataset Information

Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy.

Publications

Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy.

Similar Datasets

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