A MUC1/IL-18 DNA vaccine induces anti-tumor immunity and increased survival in MUC1 transgenic mice

MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model

“…Recent description of MUC1 as a target for cytotoxic T lymphocytes (CTLs) has raised interest in using this protein as a target for immunotherapy [4][5][6][7][8][9][10][11][12][13][14]. Several preclinical and clinical trials targeting the tumor-associated MUC1 antigen have elicited strong anti-tumor CTLs [1,2,12,[14][15][16][17][18][19][20][21][22][23][24]. Importantly, there have been several reports of two HLA-A2 binding peptides derived from the MUC1 protein [25][26][27].…”

Induction of antigen-specific CTL and antibody responses in mice by a novel recombinant tandem repeat DNA vaccine targeting at mucin 1 of pancreatic cancer

“…Some DNA vaccines based on full-length MUC1 (Zhang et al 2008;Acres and Limacher 2005) have been constructed and could generate immune responses specific for MUC1-expressing cancer cells in both mice and human beings (Yamamoto et al 2005;Sangha and Butts 2007;Tang and Apostolopoulos 2008). However, some unfavorable sequences in whole MUC1 gene might cause the inhibition of the vaccine induced immunity (Sharav et al 2007;Tang and Apostolopoulos 2008); therefore, DNA vaccines based on full-length MUC1 are insufficient to protect the host from attacking by tumor cells expressing MUC1 (Mukherjee et al 2001;Snyder et al 2006). Therefore, the new TR DNA vaccine, just encoding one TR polypeptide, is expected to eliminate immunosuppression of unfavorable sequences and to augment the MUC1-specific immune responses.…”

“…Mice immunized with the MUC1-TR peptides (Zhang et al 1996), MUC1-mannan fusion protein (Lees et al 2000), or dendritic cells transfected with MUC1 peptides (Lepisto et al 2008) could develop both humoral and cellular immune responses and partly suppress the growth of MUC1-expressing tumors. Although MUC1-specific antibodies and/or CTLs were detected in host and protected the host from attacking by tumor cells that express MUC1 (Johnen et al 2001), they were not adequate to generate effective anti-tumor immunity to totally inhibit the growth of tumor (Brossart et al 2000;Snyder et al 2006). Moreover, clinical trials with MUC1 showed that MUC1 is a relatively poor immunogen in human beings (Kawaoka et al 2008;Sugiura et al 2008) and that the induction of clinically effective anti-tumor immune responses had not been achieved.…”

“…Reports of MUC1 DNA vaccines are insufficient, and most vaccines have been constructed with the full-length MUC1 cDNA (Johnen et al 2001;Snyder et al 2006;Sugiura et al 2008). Some showed that MUC1-specific CTLs were undetectable after MUC1 DNA immunization but became evident only after tumor challenge.…”

Effective anti-tumor responses induced by recombinant bacillus Calmette–Guérin vaccines based on different tandem repeats of MUC1 and GM-CSF

“…MUC1 is a type I transmembrane protein and carries the important variable-number tandem repeat (VNTR) epitopes for inducing cytotoxic T lymphocytes (Taylor et al, 2002;Baldus et al, 2004). Many approaches targeting MUC1 for breast tumor immunotherapy have been made, including vaccination with peptides (Zhang et al, 1996;Soares et al, 2001), proteins/fusion proteins (Acres et al, 2000;Mushenkova et al, 2005), MUC1-expressing recombinant viruses (Scholl et al, 2000), dendritic cells (DCs) (Koido et al, 2000), DC/tumor cell fusions (Gong et al, 1998;Chen et al, 2003), and DNA vaccines (Graham et al, 1996;Plunkett et al, 2004;Snyder et al, 2006). However, preclinical trials with MUC1 showed that MUC1 is a relatively poor immunogen in human beings.…”