Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=C4144616&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
NEW GLIOMA-ASSOCIATED AUTO-ANTIBODIES #MMPMIDC4144616
Fueyo J; Conrad C; Gomez-Manzano C; Yung WA; Tufaro F; Lang F
Neuro Oncol 2014[Jul]; 16 (Suppl 3): iii41 PMIDC4144616show ga
BACKGROUND: Accumulating evidence has demonstrated that the immune system can recognize the antigenic changes in cancer cells, and further develop autoantibodies against these tumor-associated antigens (TAAs). Therefore, these cancer-associated autoantibodies might be used to identify the antigenic changes of cellular proteins involved in the transformation process. Antibodies to tumor antigens have advantages over other serum proteins as potential cancer biomarkers as they are highly specific and easily identified with high quality secondary reagents. Currently, there is a paucity of studies on autoantibodies against TAAs in gliomas. Here we examined the antibodies against TAAs in a Phase I clinical trial of patients with recurrent gliomas treated with the intratumoral injection of Delta-24-RGD oncolytic adenovirus (Fred Lang, Neurosurgery, MDACC, Director of the Trial). METHODS: Sera from 37 patients were analysed before the administration of Delta-24-RGD and then at several time points after the administration of the adenovirus. A solid phase-modified ELISA was used to assess antibodies against the following 31 antigens: BRAF, CABYR, CRISP3, CSAG2, DHFR, FHLT17, GAGE1, LDHC, MAGEA1, MAGEA3, MAGEA4, MAGEB6, MAPK1, MUC1, NLRP4, NYESO1, p53, PBK, PRAME, SOX2, SPANXA1,SSX2, TSGA10, TSSK6, TULP2, XAGE2, ZNF165. Expression of the proteins in tumors was confirmed using western blot and/or immunohistochemistry. Data were the result of at least two independent experiments. RESULTS: 1. The majority of the patients with recurrent gliomas harbor antibodies against TAAs. 2. The titer of antibodies against TAAs drastically decreased after total resection of the tumor. 3. After surgery the antibodies became again detectable predicting relapse. 4. 80% of patients' sera have antibodies against cancer testis antigens including NYESO1 and MAGE. 5. 60% of the patients showed antibodies against MAGEA1 o MAGEA3. 6. 40% of patients were positive for NYESO1 antibodies. 7. A small percentage of patients have antibodies against BRAF or SOX2. CONCLUSIONS: We report for the first time a systematic analysis of cancer-associated antibodies in patients with recurrent gliomas treated with oncolytic adenoviruses. As illustrated in this study, the serological screening of patients using solid phase ELISA for well characterized antigens offers new opportunities for analyzing the repertoire of the humoral immune response to human gliomas. Many of the listed antibodies were never analyzed before in gliomas. More intensive screening of patients after surgery may include frequent antibody screening (i.e. every 3?6 months) as an adjunct to serial MRIs. Of further clinical relevance several of the cancer/testis antigens identified are promising targets for cancer vaccines. SECONDARY CATEGORY: Tumor Biology.
free
free
free
Neuro+Oncol 2014 ; 16 (Suppl 3): iii41
