[Lani]

with her2 vaccines in rats seems to be due to "survival of the fittest" of clonogenic group of cells which have epigenetically silenced her2 (methylation of gene which essentially hides it from being transcribed and made into the gene product). Thus her2 doesn't have to be lost to be "invisible" to herceptin or her2vaccines

1: Eur J Immunol. 2007 Feb 16; [Epub ahead of print] Links
HER-2/neu antigen loss and relapse of mammary carcinoma are actively induced by T cell-mediated anti-tumor immune responses.

Kmieciak M,
Knutson KL,
Dumur CI,
Manjili MH.
Department of Microbiology & Immunology , VCU School of Medicine, Massey Cancer Center, Richmond, VA.
Induction of tumor-specific immune responses results in the inhibition of tumor development. However, tumors recur because of the tumor immunoediting process that facilitates development of escape mechanisms in tumors. It is not known whether tumor escape is an active process whereby anti-tumor immune responses induce loss or downregulation of the target antigen in the antigen-positive clones. To address this question, we used rat neu-overexpressing mouse mammary carcinoma (MMC) and its relapsed neu antigen-negative variant (ANV). ANV emerged from MMC under pressure from neu-specific T cell responses in vivo. We then cloned residual neu antigen-negative cells from MMC and residual neu antigen-positive cells from ANV. We found marked differences between these neu-negative clones and ANV, demonstrating that the residual neu-negative clones are probably not the origin of ANV. Since initial rejection of MMC was associated with the presence of IFN-gamma-secreting T cells, we treated MMC with IFN-gamma and showed that IFN-gamma could induce downregulation of neu expression in MMC. This appears to be due to methylation of the neu promoter. Together, these data suggest that neu antigen loss is an active process that occurs in primary tumors due to the neu-targeted anti-tumor immune responses.
PMID: 17304628 [PubMed - as supplied by publisher]