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…
3,007 Citations
CTLA-4 and PD-1 Control of T-Cell Motility and Migration: Implications for Tumor Immunotherapy
- BiologyFront. Immunol.
- 2018
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
- BiologyClinical Cancer Research
- 2010
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.
- BiologyAgents and actions. Supplements
- 1998
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.
Tuning tumor-specific T-cell activation: a matter of costimulation?
- Biology, MedicineTrends in immunology
- 2002
Immune response enhancement by in vivo administration of B7.2Ig, a soluble costimulatory protein.
- BiologyClinical immunology
- 1999
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
- BiologyThe Journal of Immunology
- 2001
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.
- Biology, MedicineProceedings of the National Academy of Sciences of the United States of America
- 1998
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.
Anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) immunotherapy for the treatment of prostate cancer.
- Biology, MedicineUrologic oncology
- 2006
CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy.
- Biology, MedicineAnnual review of immunology
- 2001
Newly emerging data suggest that inhibitory signals mediated by CTLA-4 not only can determine whether T cells become activated, but also can play a role in regulating the clonal representation in a polyclonal response.
References
SHOWING 1-10 OF 53 REFERENCES
Manipulation of costimulatory signals to enhance antitumor T-cell responses.
- Biology, MedicineCurrent opinion in immunology
- 1995
Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4
- Biology, MedicineCell
- 1992
Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells.
- Biology, MedicineScience
- 1993
Results suggest that B7 expression renders tumor cells capable of effective antigen presentation, leading to their eradication in vivo.
Specificity and longevity of antitumor immune responses induced by B7-transfected tumors.
- BiologyCancer research
- 1994
It is found that the immunity induced by K1735 is not restricted to the parental tumor cells but is effective against an additional melanoma line and an unrelated fibrosarcoma as well and irradiation severely diminishes the effectiveness of B7-positive tumor cells as immunogens.
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation
- BiologyThe Journal of experimental medicine
- 1995
It is shown here that the presence of low levels of B7-2 on freshly explanted T cells can partially inhibit T cell proliferation, and this inhibition is mediated by interactions with CTLA-4, which strongly suggests that the outcome of T cell antigen receptor stimulation is regulated by CD28 costimulatory signals, as well as inhibitory signals derived from CTla-4.
CTLA4 mediates antigen-specific apoptosis of human T cells.
- Biology, MedicineProceedings of the National Academy of Sciences of the United States of America
- 1995
It is demonstrated that cross-linking of the inducible T-cell surface molecule CTLA4 can mediate apoptosis of previously activated human T lymphocytes, and Regulation of this pathway may provide a novel therapeutic strategy to delete antigen-specific activated T cells.
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
- Biology, MedicineScience
- 1995
Although CTLA-4-deficient T cells proliferated spontaneously and strongly when stimulated through the T cell receptor, they were sensitive to cell death induced by cross-linking of the Fas receptor and by gamma irradiation, and is vital for the control of lymphocyte homeostasis.
Constitutive expression of B7 restores immunogenicity of tumor cells expressing truncated major histocompatibility complex class II molecules.
- BiologyProceedings of the National Academy of Sciences of the United States of America
- 1993
The role of B7 activation molecule is illustrated in stimulating potent tumor-specific CD4+ T cells that mediate rejection of wild-type tumors and provides a theoretical basis for immunotherapy of established tumors.
Dendritic cells as initiators of tumor immune responses: a possible strategy for tumor immunotherapy?
- BiologyImmunology today
- 1995