In:
The Journal of Immunology, The American Association of Immunologists, Vol. 178, No. 1_Supplement ( 2007-04-01), p. S91-S91
Abstract:
Activation induced cytidine deaminase (AID) is an essential enzyme that controls the generation of antibody diversity in B cells and is considered a general gene mutator. Using transgenic T cells specific to P1A (P1CTL) to treat mice with large established plasmacytoma J558 tumors, we frequently observed mutations in P1A antigenic epitope, which lead to cancer cell evasion of destruction by P1CTL. To determine whether AID plays a role in CTL-mediated rejection of plasmacytoma, we generated AID-silenced plasmacytoma J558 cells and controls and tested whether large established AID-silenced J558 tumors could be rejected by P1CTL. Complete rejection of large established tumors by P1CTL was rare (0–10%) in mice with AID+ J558 tumors while the rejection rates were 30–90% in mice with AID-silenced J558 tumors. AID knock down did not reduce mutation rate of P1A gene, but rather caused more genetic instability and altered gene expression profile. Notably, we observed strong up-regulation of OX-2 (CD200) gene and down-regulation of CaMKII-δ gene in AID-silenced J558 cells, whose roles may be related to enhanced immune rejection of AID-silenced J558 tumors. Our results suggest that simultaneously targeting AID in CTL-targeted therapy of myeloma or other AID+ tumors may be of therapeutic value.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.178.Supp.50.8
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2007
detail.hit.zdb_id:
1475085-5
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