Immunization with two recombinant Bacillus Calmette-Guérin vaccines that combine the expression of multiple tandem repeats of mucin-1 and colony stimulating-factor suppress breast tumor growth in mice

Abstract

rBCG-MVNTR4-CSF and rBCG-MVNTR8-CSF vaccines may be good candidates for breast tumor immunotherapy.

Correlation Between Auto-antibodies to Survivin and MUC1 Variable Number Tandem Repeats in Colorectal Cancer

“…There are several reports showing that survivin autoantibodies have been detected in some cancer patients, such as lung, breast and colorectal cancer patients (AlJoudi et al, 2006;Karanikas, 2009;Chen et al, 2010), as well antibodies to MUC1 (Hirasawa et al, 2000;Tang et al, 2010). Moreover, several studies have revealed that vaccines targeting survivin or MUC1 VNTR can elicit both specific humoral and cellular immune responses both in pre-clinical and clinical trials (Tang et al, 2008;Yuan et al, 2010;Ishizaki et al, 2011;Kameshima et al, 2011), indicating that they are potent cancer vaccine targets. However, the correlations between auto-antibodies to survivin and MUC1 VNTR remain unknown.…”

Th1 Cytokine-Secreting Recombinant Bacillus Calmette-Guérin: Prospective Use in Immunotherapy of Bladder Cancer

“…SCID mice reconstituted with human PBL followed by immunization with the rBCG strains developed MUC1-specific cellular immune respnses and enhanced protection against MUC1-positive human breast cancer xenografts compared to control mice reconstituted with human PBL and immunized with non-cytokine secreting BCG. Studies have also www.intechopen.com demonstrated that the antitumor effects of the rBCG strains were correlated with the number of MUC1 tandem repeats delivered by BCG ( a Yuan et al, 2009Yuan et al, , 2010. These results suggest that these MUC1 rBCG strains coexpressing Th1-stimulating cytokines are promising candidates as breast cancer vaccines and thus deserve further investigation.…”

“…Most of these cytokine-and chemokine-secreting rBCG strains showed their abilities to enhance BCG-induced cellular immune responses including Th1 cytokine production, cellular cytotoxicity, DC activation, and anti-BCG or anti-M.tb infection. Some of them even showed their antitumor effects in animal models of melanoma (Duda et al, 1995), breast cancer (Chung et al, 2003;a Yuan et al, 2009, Yuan et al, 2010, and bladder cancer (Arnold et al, 2004). Certain cytokine-secreting rBCG strains also induced humoral immune responses and Th2 cytokine production other than cellular immune responses in vitro and in vivo.…”

“…In addition, we further observed that mice primed with the rBCG-PSA strain and boosted with Ad-PSA, a replicationdefective adenoviral vector carrying the full-length PSA coding sequence (Elzey et al, 2001), developed enhanced PSA-specific CTL activity and IFN-γ expressing CD4 + and CD8 + T cells (our unpublished observations). Several studies including ours have also demonstrated that BCG could be engineered to express mucin-1 (MUC1), a candidade tumor-associated antigen for breast cancer and other epithelial adenocarcinomas, in a manner of multiple tandem repeats with coexpression of IL-2, GM-CSF or CD80 (He et al, 2002;Chung et al, 2003; Yuan et al, 2009Yuan et al, , 2010. Severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood lymphocytes (PBL) followed by immunization with these MUC1 expressing rBCG strains developed specific protective immunity against MUC1-positive human breast cancer xenografts.…”

“…However, it was not until recently that the potential of rBCG for treating cancer has gained further appreciation. We and others have developed rBCG strains that deliver the breast cancer-associated antigen MUC1 in a form of multiple tandem repeats with coexpression of human IL-2 or human GM-CSF (He et al, 2002;Chung et al, 2003;a Yuan et al, 2009Yuan et al, , 2010. SCID mice reconstituted with human PBL followed by immunization with the rBCG strains developed MUC1-specific cellular immune respnses and enhanced protection against MUC1-positive human breast cancer xenografts compared to control mice reconstituted with human PBL and immunized with non-cytokine secreting BCG.…”