Adjuvant effect of anti-4-1BB mAb administration in adoptive T cell therapy of cancer

Li, Qiao; Iuchi, Takekazu; Jure-Kunkel, Maria; Chang, Alfred E.

doi:10.7150/ijbs.3.455

Cited by 15 publications

(12 citation statements)

References 35 publications

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“…Zhang et al reported that anti-CD137 mAb enhanced the proliferation, survival and function of activated B cells in vitro 33 . It would seem logical that the in vivo administration of anti-CD137 concomitantly with effector B cell transfer could enhance their antitumor efficacy in a similar fashion to adoptive T cell therapy which we have reported 34 .…”

Section: Discussionmentioning

confidence: 76%

Adoptive Transfer of Tumor Reactive B Cells Confers Host T-Cell Immunity and Tumor Regression

Lao

Pan

et al. 2011

Clinical Cancer Research

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137

120

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Purpose We investigated the antitumor reactivity of adoptively transferred effector B cells and the mechanisms by which they may mediate tumor regression in a spontaneous metastases model. Experimental Design 4T1 breast cancer cells were inoculated into the flanks of syngeneic Balb/C mice to prime draining lymph nodes. Tumor-draining lymph nodes (TDLN) were harvested and B cells activated ex vivo with LPS and anti-CD40 mAb. These activated B cells were adoptively transferred into mice inoculated with 4T1 tumor in the mammary fat pad. The induction of host T cell immunity was evaluated. Results Activated 4T1 TDLN B cells secreted IgG in response to tumor cells which was immunologically specific. These activated B cells were capable of mediating specific lysis of tumor cells in vitro. Transfer of these activated B cells alone mediated the inhibition of spontaneous metastases to the lung. Examination of the host revealed that the transfer of these B cells resulted in the induction of tumor specific T cell immunity as measured by cytotoxicity and cytokine (IFNγ and GM-CSF) production. The combined transfer of activated T and B cells from TDLN resulted in tumor regression, which was greater than either cell population alone, with host B cells capable of producing IgG that mediated lysis of tumor in the presence of complement. Conclusions We have found that appropriately primed B cells can mediate tumor regression by itself and confers host T cell antitumor immunity. Furthermore, effector B cells can serve as a useful adjunct in adoptive T cell therapy.

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Section: Discussionmentioning

confidence: 76%

Adoptive Transfer of Tumor Reactive B Cells Confers Host T-Cell Immunity and Tumor Regression

Lao

Pan

et al. 2011

Clinical Cancer Research

Self Cite

137

120

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“…One approach used coinhibitory blockade combined with therapeutic vaccination using irradiated tumor cells that were transduced to secrete either GM-CSF or FMS-like tyrosine kinase 3 ligand [85]. Another example is the augmented therapeutic efficacy when combining therapeutic cancer vaccines with agonistic 4-1BB antibody therapy [86]. These results in cancer preclinical models have prompted significant interest in developing in vivo therapeutic interventions to block PD-1 signaling in human cancer patients.…”

Section: The Pd-1 Pathwaymentioning

confidence: 98%

Tumor immune surveillance and ovarian cancer

Kandalaft

Motz

Duraiswamy

et al. 2011

Cancer Metastasis Rev

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In the past few years, cancer immunotherapies have produced promising results. Although traditionally considered unresponsive to immune therapy, increasing evidence indicates that ovarian cancers are, in fact, immunogenic tumors. This evidence comes from diverse epidemiologic and clinical data comprising evidence of spontaneous antitumor immune response and its association with longer survival in a proportion of ovarian cancer patients; evidence of tumor immune evasion mechanisms and their association with short survival in some ovarian cancer patients; and finally pilot data supporting the efficacy of immune therapy. Below we will discuss lessons learned on the biology underlying ovarian cancer immune rejection or tolerance and we will discuss its association with clinical outcome. We will discuss the role of angiogenesis and the tumor endothelium on regulation of the antitumor immune response with a special emphasis on the role of vascular endothelial growth factor (VEGF) in the suppression of immunological processes, which control tumor progression and its unique crosstalk with endothelin systems, and how their interactions may shape the antitumor immune response. In addition, we will discuss mechanisms of tumor tolerance through the suppression or exhaustion of effector cells and how these could be countered in the clinic. We believe that understanding these pathways in the tumor microenvironment will lead to novel strategies for enhancing ovarian cancer immunotherapy.

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“…It is interesting that such combination pairings have not been fully explored for adoptive T cell therapy because the addition of an immunomodulating agent may significantly improve its efficacy. One example is the augmented therapeutic efficacy of adoptive T cell therapy when combined with agonistic anti-4-1BB mAb in a dose dependent manner [66]. In light of the negative correlation between prolonged in vitro culture of tumor-reactive T cells and their in vivo function [67,68], the evidence of superior antitumor immunity generated by adoptively-transferred effector cells derived from naïve rather than central memory CD8 + T cells [68], and the need to investigate in vivo priming of adoptively transferred naïve T cells, perhaps now is the time to explore various combination treatments centered around adoptive T cell therapy.…”

Section: Introductionmentioning

confidence: 99%

Features of responding T cells in cancer and chronic infection

Kim

Ahmed

2010

Current Opinion in Immunology

260

231

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Summary Ever since T cell exhaustion was initially characterized and thoroughly analyzed in the murine LCMV model, such a functional impairment has been validated in other chronic viral infections such as HIV, HCV, and HBV. In tumor immunology, it has always been postulated that tumor-reactive T cells could also become functionally exhausted due to the high tumor-antigen load and accompanying inhibitory mechanisms. However, the empirical evidences for this hypothesis have not been as extensive as in chronic infection perhaps because much of the focus on T cell dysfunction in tumor immunology has been, and appropriately so, on breaking or bypassing immune tolerance and anergy to tumor/self antigens. Based on recent reports, it is becoming clear that T cell exhaustion also plays a critical role in the impairment of antitumor immunity. In this review, we will comparatively evaluate the T cell responses in cancer and chronic infection, and the therapeutic strategies and interventions for both diseases.

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Adjuvant effect of anti-4-1BB mAb administration in adoptive T cell therapy of cancer

Cited by 15 publications

References 35 publications

Adoptive Transfer of Tumor Reactive B Cells Confers Host T-Cell Immunity and Tumor Regression

Adoptive Transfer of Tumor Reactive B Cells Confers Host T-Cell Immunity and Tumor Regression

Tumor immune surveillance and ovarian cancer

Features of responding T cells in cancer and chronic infection

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