Journal
ONCOTARGET
Volume 9, Issue 3, Pages 3996-4019Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.23583
Keywords
colon cancer; antibody; immunogen; precision diagnostics; immunotherapy
Categories
Funding
- Ontario Cancer Institute/Princess Margaret Cancer Center
- Memorial Sloan Kettering Cancer Center
- Farmer Family Foundation
- Parker Institute for Cancer Immunotherapy
- NIH/NCI Cancer Center Support Grant [P30 CA008748]
Ask authors/readers for more resources
We hypothesized that cancer tissue immunogens - antigens capable of inducing specific antibody production in patients - are promising targets for development of precision diagnostics and humoral immunotherapies. We developed an innovative immuno-proteomic strategy and identified new immunogenic markers of colon cancer. Proteins from cancers and matched normal tissues were separated by 2D gel electrophoresis and blotted with serum antibodies from the same patients. Antibody-reactive proteins were sequenced by mass spectrometry and validated by Western blotting and immunohistochemistry. 170 serum antibody-reactive proteins were identified only in cancerous but not matched normal. Among these, proteasome subunit alpha type 1 (PSA1), leucine aminopeptidase 3 (LAP3), annexin A3 (ANXA3), and maspin (serpin B5) were reproducibly found in tissues from three patients. Differential expression patterns were confirmed in samples from eight patients with various stages of colon adenocarcinoma and liver metastases. These tumor-resident proteins and/or their associated serum antibodies may be promising markers for colon cancer screening and early diagnosis. Furthermore, tumor tissue-specific antibodies could potentially be exploited as immunotherapeutic targets against cancer. More generally, proteomic profiling of antibody-inducing cancer-associated immunogens represents a powerful generic method for uncovering the tumor antigen-ome, i.e., the totality of immunogenic tumor-associated proteins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available