Dendritic Cell-Based Vaccination in Solid Cancer

Stift, Anton; Friedl, Josef; Dubsky, Peter; Bachleitner‐Hofmann, Thomas; Schueller, Gerd; Zontsich, T.; Benkoe, Thomas; Radelbauer, K.; Brostjan, Christine; Jakesz, R.; Gnant, Michael

doi:10.1200/jco.2003.02.135

Cited by 122 publications

(59 citation statements)

References 22 publications

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“…Despite relative simplicity and safety, vaccine treatments have shown very limited success [89]. Although the generation in vivo of antitumor T cells in vaccinated patients could be demonstrated by techniques such as tetramer or ELISpot assays [90][91][92], clinical responses observed from these trials were few [89]. This was consistent with the finding in murine models that the presence of even large numbers of antigen-specific T cells is insufficient to mediate tumor regression [14,93].…”

Section: Light Recruits and Sustains Effector T Cells -Combination Wisupporting

confidence: 56%

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Yü¹,

Fu²

2008

Cytokine & Growth Factor Reviews

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Metastastic diseases cause the majority of morbidity and mortality of cancer patients. Established tumors form both physical and immunological barriers to limit immune detection and destruction. Current immunotherapy of vaccination and adoptive transfer shows limited effect at least in part due to the existing barriers in the tumors and depending on the knowledge of tumor antigens. Tumor necrosis factor superfamily member 14 (TNFSF14) LIGHT interacts with stromal cells, dendritic cells, NK cells, naïve and activated T cells and tumor cells inside the tumor tissues via its two functional receptors, HVEM and lymphotoxin β receptor (LTβR). Targeting tumor tissues with LIGHT leads to augmentation of priming, recruitment, and retention of effector cells at tumor sites, directly or indirectly, to induce strong anti-tumor immunity to inhibit the growth of primary tumors as well as eradicate metastases. Intratumor treatment would break tumor barriers and allow strong immunity against various tumors without defining tumor antigens. This review summarizes recent findings to support that LIGHT is a promising candidate for an effective cancer immunotherapy.

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Section: Light Recruits and Sustains Effector T Cells -Combination Wisupporting

confidence: 56%

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Yü¹,

Fu²

2008

Cytokine & Growth Factor Reviews

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“…The MR is a marker of alternatively activated cells with enhanced cell function, mediates both pinocytosis and phagocytosis, and serves as a molecular link between innate and adaptive immune response [26]. Because DC efficiently bind sIgA [7] via a receptor with lectin-like properties [25], we were interested to know whether NK cells may bind sIgA via MR. NK cells and monocytes did not bind anti-MR Ab, whereas the MR is highly expressed on monocyte-derived DC [29], as well as on monocyte-derived M ¶ [4]. Furthermore, the percentage of NK (CD3 -CD56 + ) cells binding sIgA did not change when L-fucose, D-galactose, D-glucose, D-mannose or N-acetyl-D-glucosamine were used as inhibitors.…”

Section: Discussionmentioning

confidence: 86%

Human NK cells express Fc receptors for IgA which mediate signal transduction and target cell killing

Moţa¹,

Manciulea²,

Cosma³

et al. 2003

Eur J Immunol

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“…Despite its relative simplicity and safety, vaccine treatments have shown very limited success. 8 Although tetramer or ELISPOT assays revealed the generation of in vivo antitumor T cells in vaccinated patients, [9][10][11] clinical responses observed from these trials were few. 8 This was consistent with observations in murine models where the presence of large numbers of antigen-specific T cells was insufficient to mediate tumor regression in tumor-bearing mice.…”

Section: The Current Strategies For Cancer Immunotherapymentioning

confidence: 99%

Targeting and utilizing primary tumors as live vaccines: changing strategies

Yang

Mortenson

2011

Cell Mol Immunol

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Tumor metastases and relapse are the major causes of morbidity and mortality in cancer. Although surgery, chemotherapy and/or radiation therapy can typically control primary tumor growth, metastatic and relapsing tumors are often inaccessible or resistant to these treatments. An adaptive immune response can be generated during these conventional treatments of the primary tumor, and presumably both the primary tumor and secondary metastases share many of the same or similar antigenic characteristics recognized by the immune system. Thus, when established, this response should be able to control metastatic growth and tumor relapse. This review summarizes the mechanisms by which antitumor immune responses are generated, and recent findings supporting the hypothesis that many therapies targeting primary tumors can generate antitumor adaptive immune responses to prevent metastases and tumor relapse. Keywords: chemotherapy; immunotherapy; metastasis; radiotherapy; tumor vaccine INTRODUCTION Conventional treatments such as surgery and chemotherapy are effective means of eliminating or reducing primary tumor growth, but have not proved effective in eradicating metastases. Because metastatic disease may not respond similarly to chemotherapies used in treating the primary tumor, 1 recent research has focused on the importance of generating an antitumor immune response to control metastatic disease. Presumably, both the primary tumor and secondary metastases share many of the same or similar antigenic characteristics recognized by the immune system; yet, there has been no clear strategy formulated in which a patient's own tumor tissues is used to generate an antitumor adaptive immune response for the eradication of metastases and prevention of relapse. Once tumors metastasize, curing the disease is difficult and rare. This review summarizes recent findings supporting the hypothesis that targeting primary tumors with both conventional and new therapies can potentially generate antitumor adaptive immune responses that prevent metastases and relapse.Due to the vast number of genetic changes associated with carcinogenesis, tumors express many neo-antigens and mutated antigens. Indeed, much evidence exists to indicate that many cancers are antigenic and thus recognizable by the adaptive immune system. 2 Mere recognition by adaptive immunity, however, is insufficient, given that these antigenic cancers rarely regress spontaneously. Effective antitumor immunity depends on both the presence of tumor-reactive lymphocyte precursors and means by which these precursor lymphocytes can be activated. Most T cells with high affinity to tissue-specific antigens are deleted in the thymus or later tolerized in the peripheral

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Dendritic Cell-Based Vaccination in Solid Cancer

Abstract: These data indicate that vaccination with autologous tumor-pulsed DCs generated from peripheral blood is safe and can induce tumor-specific cellular cytotoxicity. Clinical responses are achievable, even in patients with advanced disease.

Cited by 122 publications

References 22 publications

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Human NK cells express Fc receptors for IgA which mediate signal transduction and target cell killing

Targeting and utilizing primary tumors as live vaccines: changing strategies

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