Clinical trials with α-galactosylceramide (KRN7000) in advanced cancer

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

Abstract

For over a century, research has sought ways to boost the immune system of cancer patients in order to eradicate tumors that arose after escaping presumptive immunosurveillance. With increasing knowledge of the immune system, immunotherapeutic strategies to break tolerance to the tumor evolved from largely nonspecific to more specific and increasingly potent forms of cancer vaccination. Overall however, immunotherapeutic strategies for the treatment of cancer have had limited clinical success and an urgent need exists, therefore, to introduce more effective, knowledge-based therapeutic approaches. Invariant natural killer T (iNKT) cells constitute an evolutionary conserved T lymphocyte lineage with dominant immunoregulatory and antitumor effector cell properties. iNKT specifically recognize the glycolipid α-galactosylceramide (α-GalCer/KRN7000) in the context of the CD1d antigen-presenting molecule resulting in their activation. Activated iNKT have been shown to promote the development of a long-lasting Th1-biased proinflammatory antitumor immune response in a variety of murine tumor-metastasis models of liver, lung and lymph nodes, including colon and lung carcinoma, lymphoma, sarcoma, and melanoma, suggesting broad clinical applicability. Here, we will provide an overview of the preclinical data of α-GalCer that formed the basis for subsequent clinical trials in advanced cancer patients, review these clinical trials, focusing on our own experience with α-GalCer, and discuss future perspectives.

Original languageEnglish
Title of host publicationNatural Killer T cells
Subtitle of host publicationBalancing the Regulation of Tumor Immunity
PublisherSpringer New York
Pages169-183
Number of pages15
ISBN (Electronic)9781461406136
ISBN (Print)9781461406129
DOIs
Publication statusPublished - 1 Jan 2012

Cite this

Schneiders, Famke L. ; Scheper, Rik J. ; Bontkes, Hetty J. ; von Blomberg, B. Mary E. ; Eertwegh, Alfons J.M. ; de Gruijl, Tanja D. ; Van Der Vliet, Hans J. / Clinical trials with α-galactosylceramide (KRN7000) in advanced cancer. Natural Killer T cells: Balancing the Regulation of Tumor Immunity. Springer New York, 2012. pp. 169-183
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abstract = "For over a century, research has sought ways to boost the immune system of cancer patients in order to eradicate tumors that arose after escaping presumptive immunosurveillance. With increasing knowledge of the immune system, immunotherapeutic strategies to break tolerance to the tumor evolved from largely nonspecific to more specific and increasingly potent forms of cancer vaccination. Overall however, immunotherapeutic strategies for the treatment of cancer have had limited clinical success and an urgent need exists, therefore, to introduce more effective, knowledge-based therapeutic approaches. Invariant natural killer T (iNKT) cells constitute an evolutionary conserved T lymphocyte lineage with dominant immunoregulatory and antitumor effector cell properties. iNKT specifically recognize the glycolipid α-galactosylceramide (α-GalCer/KRN7000) in the context of the CD1d antigen-presenting molecule resulting in their activation. Activated iNKT have been shown to promote the development of a long-lasting Th1-biased proinflammatory antitumor immune response in a variety of murine tumor-metastasis models of liver, lung and lymph nodes, including colon and lung carcinoma, lymphoma, sarcoma, and melanoma, suggesting broad clinical applicability. Here, we will provide an overview of the preclinical data of α-GalCer that formed the basis for subsequent clinical trials in advanced cancer patients, review these clinical trials, focusing on our own experience with α-GalCer, and discuss future perspectives.",
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Clinical trials with α-galactosylceramide (KRN7000) in advanced cancer. / Schneiders, Famke L.; Scheper, Rik J.; Bontkes, Hetty J.; von Blomberg, B. Mary E.; Eertwegh, Alfons J.M.; de Gruijl, Tanja D.; Van Der Vliet, Hans J.

Natural Killer T cells: Balancing the Regulation of Tumor Immunity. Springer New York, 2012. p. 169-183.

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

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N2 - For over a century, research has sought ways to boost the immune system of cancer patients in order to eradicate tumors that arose after escaping presumptive immunosurveillance. With increasing knowledge of the immune system, immunotherapeutic strategies to break tolerance to the tumor evolved from largely nonspecific to more specific and increasingly potent forms of cancer vaccination. Overall however, immunotherapeutic strategies for the treatment of cancer have had limited clinical success and an urgent need exists, therefore, to introduce more effective, knowledge-based therapeutic approaches. Invariant natural killer T (iNKT) cells constitute an evolutionary conserved T lymphocyte lineage with dominant immunoregulatory and antitumor effector cell properties. iNKT specifically recognize the glycolipid α-galactosylceramide (α-GalCer/KRN7000) in the context of the CD1d antigen-presenting molecule resulting in their activation. Activated iNKT have been shown to promote the development of a long-lasting Th1-biased proinflammatory antitumor immune response in a variety of murine tumor-metastasis models of liver, lung and lymph nodes, including colon and lung carcinoma, lymphoma, sarcoma, and melanoma, suggesting broad clinical applicability. Here, we will provide an overview of the preclinical data of α-GalCer that formed the basis for subsequent clinical trials in advanced cancer patients, review these clinical trials, focusing on our own experience with α-GalCer, and discuss future perspectives.

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BT - Natural Killer T cells

PB - Springer New York

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Schneiders FL, Scheper RJ, Bontkes HJ, von Blomberg BME, Eertwegh AJM, de Gruijl TD et al. Clinical trials with α-galactosylceramide (KRN7000) in advanced cancer. In Natural Killer T cells: Balancing the Regulation of Tumor Immunity. Springer New York. 2012. p. 169-183 https://doi.org/10.1007/978-1-4614-0613-6_10