Background Human cancers employ a number of mechanisms to evade host immune responses against novel antigens generated from aberrant over-expression, mutations and/or epigenetic alterations. Humoral immunity utilizes antibodies and immune-effector cells as well as molecular immune complexes involving the complement system to mediate the killing of dysregulated cancer cells. We refer to these anti-cancer mechanisms as Humoral Immuno-Oncology (HIO). Suppression of HIO is mediated by tumor-produced proteins called HIO factors. One such factor is CA125, which was previously shown to bind IgG-type antibodies and inhibit their antibody dependent (ADCC) and complement dependent (CDC) cellular cytotoxic activities. Using a combination of experimental screening and literature searches, we screened a number of proteins that have been produced by tumors and associated with a variety of cancer indications to determine if they could impact HIO. Herein, we describe the initial characterization of soluble ICAM-1 (sICAM-1), a tumor antigen capable of binding IgG-type antibodies that inhibits their immune-effector activity. Methods Deletion and site-directed mutatgenesis of the heavy constant domain of IgG1 was performed and constructs expressed as GST fusions in 293F cells. Recombinant proteins were then used in direct binding and competition ELISA formats to determine amino acid residues essential for binding of HIO-3. Constant region mutants that lost HIO-3 binding were then generated to whole IgG constructs for in vitro characterization of HIO-3 resistance. Results Amino acid substitutions in this domain were able to abrogate sICAM-1 binding and overcome ADCC suppression. Conclusions These findings highlight yet another mechanism by which tumors can suppress the host's immune system for survival and offers new concepts for developing antibody-based therapies that can aid in the treatment of various cancer indications. Moreover, the findings here offer clinical design opportunities to improve upon existing approved immune-mediated therapies for which this factor is present.

c-myb, a protooncogene prevalently expressed in the hematopoietic tissue, is a transcription factor that contains a DNA-binding domain and an acidic domain and is able to transactivate specific viral and cellular genes. In this report, we show that c-myb can stimulate apoptosis in both the murine promyelocytic 32D and the human osteosarcoma SAOS2 cell lines when coexpressed with p53. Apoptosis is accompanied by increased transactivation of the cell death-associated BAX gene. This effect is c-myb specific, because B-myb is not able to cooperate with p53 in the induction of BAX transcription and apoptosis. Immunoprecipitation studies and gel shift analysis indicate that c-myb does not directly interact with the BAX promoter or the p53 protein but, rather, cooperates through an indirect mechanism. Consistent with the existence of a functional link between c-myb and p53, we also observed that c-myb represses p53-induced activation of the WAF-1 promoter and induces proliferation of SAOS2 cells growth arrested by p53. These results might contribute to the elucidation of the mechanisms underlying p53-dependent pathways of oncogene-induced apoptosis and provide a further example of DNA-binding independent myb activity.