We think that the success of complete tumor rejection is in combined therapeutic approach: combining the most potent multi-epitope specific CD8 CTL vaccine with the most potent reversal of tumor induced immune suppression. In this combination multi-epitope specific CD8 CTL are generated by gp96-Ig-secreting tumor cells which now can perform their task of killing tumor cells without interference by tumor induced suppression signals. We are using engineered tumor cells secreted fusion protein, gp96-Ig, and testing it as CTL-inducing vaccine. Currently we are also investigating the novel approach of using anti-hypoxia in combination with gp96-Ig vaccination. Effectiveness of gp96-Ig vaccination in combination with 60% oxygen for the treatment of large established tumor burdens is highly innovative and we believe the combination therapy with gp96-Ig may foretell a break through with significant impact on the cancer field with benefits for patients.