Responses to the p53 Self-Tumor Antigen CTLA-4 Blockade Enhances the CTL

Combination therapy of established tumors by antibodies targeting immune activating and suppressing molecules.

The blockade of immune suppression against antitumor responses is a particularly attractive strategy when combined with agents that promote tumor-specific CTLs. In this study, we have attempted to further improve the CTL induction and potent antitumor efficacy of a combination mAb-based therapy (termed "trimAb therapy") that comprises tumor cell death-inducing anti-death receptor 5 mAb and immu...

Tumor Model Targeting p53 in an Established Murine Effect of an Attenuated Poxvirus Vaccine CTLA-4 Blockade Enhances the Therapeutic

Two distinct pathways of immuno-modulation improve potency of p53 immunization in rejecting established tumors.

The p53 gene product is overexpressed by almost 50% of cancers, making it an ideal target for cancer immunotherapy. We previously demonstrated rejection of established p53-overexpressing tumors without stimulating autoimmunity by immunization with modified vaccinia Ankara-expressing murine p53 (MVAp53). Tumor rejection was enhanced through antibody-mediated CTL-associated antigen 4 (CTLA-4) blo...

Generation of antitumor immunity by cytotoxic T lymphocyte epitope peptide vaccination, CpG-oligodeoxynucleotide adjuvant, and CTLA-4 blockade.

Although peptide immunization often leads to the induction of strong T-cell responses, it is seldom effective against established tumors. One possibility is that these T-cell responses are not strong enough or do not last sufficiently long to have an effect in tumor eradication. Here, we examined the role of synthetic oligodeoxynucleotide (ODN) adjuvants containing unmethylated cytosine-guanine...

In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance.

The efficacy of therapeutic vaccination for the treatment of cancer is limited by peripheral tolerance to tumor antigens. In vivo blockade of CTLA-4, a negative regulator of T cell function, can induce the regression of established tumors and can augment the tumor rejection achieved through therapeutic vaccination. These outcomes may reflect enhanced tumor-specific T cell priming and/or interfe...