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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Zhang
Jian Gang
JG
Department of Pathology, University of California at Irvine, Irvine, CA, USA.
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
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D004806:Ependymoma / Q000235:genetics / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D011498:Protein Precursors; D012333:RNA, Messenger