Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients

Hodi, F. Stephen; Butler, Marcus O.; Oble, Darryl A.; Seiden, Michael V.; Haluska, Frank G.; Kruse, Andrea; MacRae, Suzanne; Nelson, Marybeth; Canning, Christine; Lowy, Israel; Korman, Alan J.; Lautz, David B.; Russell, Sara E.; Jaklitsch, Michael T.; Ramaiya, Nikhil H.; Chen, Teresa C.; Neuberg, Donna; Allison, James P.; Mihm, Martín C.; Dranoff, Glenn

doi:10.1073/pnas.0712237105

Cited by 596 publications

(430 citation statements)

References 37 publications

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“…35 Hence, GM-CSF-engineered tumor vaccines combined with anti-CTLA4 engendered a co-ordinated cellular and humoral immunity associated with clinically significant tumor regressions in advanced solid cancers. 36 In such regressing tumor burdens, T cell infiltrates were juxtaposed to antibody-producing B cells in long-term responders. Humoral reactivity was reported against proangiogenic cytokines such as angiopoietin-1 and -2 blocking the endothelial cell tube formation and/or macrophage inhibitory factor attenuating macrophage Tie-2 and MMP9 expression.…”

Section: Discussionmentioning

confidence: 99%

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

et al. 2013

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Immunogenic cell death induced by cytotoxic compounds contributes to the success of selected chemotherapies by eliciting a protective anticancer immune response, which is mediated by CD4 þ and CD8 þ T cells producing interferon-c. In many instances, cancer progression is associated with high titers of tumor-specific antibodies, which become detectable in the serum, but whose functional relevance is elusive. Here, we explored the role of humoral immune responses in the anticancer efficacy of anthracyclines. Chemotherapy reduced the number of tumor-infiltrating B cells, and failed to promote humoral responses against immunodominant tumor antigens. Although anthracycline-based anticancer chemotherapies failed in T cell-deficient mice, they successfully reduced the growth of cancers developing in mice lacking B lymphocytes (due to the injection of a B-celldepleting anti-CD20 antibody), immunoglobulins (Igs) or Ig receptors (Fc receptor) due to genetic manipulations. These results suggest that the humoral arm of antitumor immunity is dispensable for the immune-dependent therapeutic effect of anthracyclines against mouse sarcoma. In addition, we show here that the titers of IgA and IgG antibodies directed against an autoantigen appearing at the cell surface of tumor cells post chemotherapy (calreticulin, CRT) did not significantly increase in patients treated with anthracyclines, and that anti-CRT antibodies had no prognostic or predictive significance. Collectively, our data indicate that humoral anticancer immune responses differ from cellular responses in, thus far, that they do not contribute to the success of anthracycline-mediated anticancer therapies in human breast cancers and mouse sarcomas.

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Section: Discussionmentioning

confidence: 99%

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

et al. 2013

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“…Using Fc receptor-deficient mice, the anti-tumor activity of anti-CTLA-4 mAb was shown to be dependent on antibody-dependent cellular cytotoxicity of Treg cells in tumor tissues instead of affecting re-activation of Tconv cells [61][62][63]. In cancer patients, strong correlations have been reported between the clinical efficacy of Ipilimumab and reduction of Treg cell numbers in tumor tissues [64][65]. It is likely that the Treg-depleting effect of anti-CTLA-4 mAb targets effector Treg cells, which are abundant in tumor tissues and express high levels of CTLA-4.…”

Section: Checkpoint Blockade Antibody With Possible Treg-depleting Efmentioning

confidence: 99%

Regulatory T cells in cancer immunotherapy

Nishikawa

Sakaguchi

2014

Current Opinion in Immunology

608

563

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“…However, because of their tendency to promote tumor tolerance, therapeutic cancer vaccines such as antigen-specific vaccines and cytokine-based whole tumor-cell vaccines remain in development [1]. Tumor tolerance is established through immunoregulatory molecules, including CTLA-4, and cells, including CD4 + CD25 + Foxp3 + regulatory T-cells (Tregs), both of which have served as immunotherapeutic targets [2][3][4][5][6]. For example, treatment with anti-CTLA-4 monoclonal antibody is associated with augmented anti-tumor immunity in a subset of patients previously vaccinated with autologous tumor cells [2,3].…”

Section: Introductionmentioning

confidence: 99%

The inhibition of the T-cell immunoglobulin and mucin domain 3 (Tim3) pathway enhances the efficacy of tumor vaccine

Lee

Woo

Heo

et al. 2010

Biochemical and Biophysical Research Communications

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Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients

Cited by 596 publications

References 37 publications

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

Regulatory T cells in cancer immunotherapy

The inhibition of the T-cell immunoglobulin and mucin domain 3 (Tim3) pathway enhances the efficacy of tumor vaccine

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