Enhancement of Antitumor Immunity by CTLA-4 Blockade

@article{Leach1996EnhancementOA,
  title={Enhancement of Antitumor Immunity by CTLA-4 Blockade},
  author={Dana R. Leach and Matthew F. Krummel and James P. Allison},
  journal={Science},
  year={1996},
  volume={271},
  pages={1734 - 1736}
}
One reason for the poor immunogenicity of many tumors may be that they cannot provide signals for CD28-mediated costimulation necessary to fully activate T cells. [] Key Result Here, in vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors. Furthermore, this rejection resulted in immunity to a secondary exposure to tumor cells. These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune…

[The role of co-inhibitory signals driven by CTLA-4 in immune system].

To better understand the promising future and the limits of this immunotherapy, this review dissects the molecular inhibitory mechanisms induced by CTLA-4 in T cells.

CTLA-4 and PD-1 Control of T-Cell Motility and Migration: Implications for Tumor Immunotherapy

Data implicating CTLA-4 and PD-1 in the motility of T-cells is reviewed with a specific reference to the potential exploitation of these pathways for more effective tumor infiltration and eradication.

Two Distinct Mechanisms of Augmented Antitumor Activity by Modulation of Immunostimulatory/Inhibitory Signals

This study shows that combined treatment with different immune modulators can augment antitumor immune responses and provides justification for exploring anti-CTLA-4/anti-GITR mAb combination treatment in the clinic.

The complexity of the B7-CD28/CTLA-4 costimulatory pathway.

In vivo studies indicate the therapeutic potential of manipulating this important, but complex, immunoregulatory pathway and reveal a previously unsuspected means by which costimulation is involved in the maintenance and breakdown of self-tolerance.

Immune response enhancement by in vivo administration of B7.2Ig, a soluble costimulatory protein.

Using a mouse model, this work suggests that soluble forms of human B7.2 protein may provide a straightforward and practical method of supplying optimal costimulation during clinical immunotherapy.

CTLA-4 Blockade Enhances the CTL Responses to the p53 Self-Tumor Antigen1

It was found that blockade of CTLA-4 engagement at the time of antigenic stimulation induced a vigorous amplification of the CTL responses to p53 as well as proportionate expansion of the memory T cell pool.

CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma.

The combination of both CTLA-4 blockade and a vaccine consisting of granulocyte-macrophage colony-stimulating factor-expressing SM1 cells resulted in regression of parental SM1 tumors, despite the ineffectiveness of either treatment alone.
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    Proceedings of the National Academy of Sciences of the United States of America
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