TITLE:
Carbohydrate-associated epitope-based anti-cancer drugs and vaccines
AUTHORS:
Gregory Lee, Cheng-Yuan Huang, Song-Nan Chow, Chin-Hsiang Chien
KEYWORDS:
Anti-Cancer Drugs; Anti-Cancer Vaccines; Anti-Idiotype; CA215; Carbohydrate-Associated Epitope; Immunodominance; RP215
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.9A,
September
11,
2013
ABSTRACT: RP215 is one of the three thousand monoclonal antibodies
(Mabs) which were generated against the OC-3-VGH ovarian cancer cell line.
RP215 was shown to react with a carbohydrate-associated epitope located
specifically on glycoproteins, known as CA215, from cancer cells. Further
molecular analysis by matrix
adsorption laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that CA215 consists mainly of immunoglobulin super-family
(IgSF) proteins, including immunoglobulins, T-cell receptors, and cell
adhesion molecules, as well as several other unrelated proteins. Peptide
mappings and glycoanalysis were performed with CA215 and revealed high-mannose
and complex bisecting structures with terminal sialic acid in N-glycans. As
many as ten O-glycans, which are structurally similar to those of mucins, were
also identified. In addition, two additional O-linked glycans were exclusively
detected in cancerous immunoglobulins but not in normal B cell-derived immunoglobulins.
Immunizations of mice with purified CA215 resulted in the predominant
generation of RP215-related Mabs, indicating the immunodominance of this
carbohydrate-associated epitope. Anti-idiotype (anti-id) Mabs of RP215, which
were generated in the rat, were shown to contain the internal images of the
carbohydrate-associated epitope. Following immunizations of these anti-id
Mabs in mice, the resulting anti-anti-id (Ab3) responses in mice were found to be immunologically similar to
that of RP215. Judging from these observations, anti-id Mabs, which
carry the internal image of the RP215-specific epitope, may be suitable
candidates for anticancer vaccine development in humans.