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Phase I study of α-galactosylceramide-pulsed antigen presenting cells administration to the nasal submucosa in unresectable or recurrent head and neck cancer

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Abstract

Background

Human Vα24 natural killer T (NKT) cells are activated by the specific ligand, α-galactosylceramide (α-GalCer), in a CD1d-dependent manner. Potent anti-tumor activity of activated NKT cells has been previously demonstrated.

Methods

We conducted a phase I study with α-GalCer-pulsed antigen presenting cells (APCs) administered in the nasal submucosa of patients with head and neck cancer, and evaluated the safety and feasibility of such a treatment. Nine patients with unresectable or recurrent head and neck cancer received two treatments 1 week apart, of 1 × 108 of α-GalCer-pulsed autologous APCs into the nasal submucosa.

Results

During the clinical study period, no serious adverse events (Common Terminology Criteria for Adverse Events version 3.0 greater than grade 3) were observed. After the first and the second administration of α-GalCer-pulsed APCs, an increased number of NKT cells was observed in four patients and enhanced natural killer activity was detected in the peripheral blood of eight patients.

Conclusion

The administration of α-GalCer-pulsed APCs into the nasal submucosa was found to be safe and induce anti-tumor activity in some patients.

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Abbreviations

α-GalCer:

α-Galactosylceramide

APCs:

Antigen presenting cells

CT:

Chemotherapy

CTCAE:

Common Terminology Criteria for Adverse Events

DCs:

Dendritic cells

NK:

Natural killer

NKT:

Natural killer T

OP:

Operation

PBMCs:

Peripheral blood mononuclear cells

PD:

Progressive disease

PR:

Partial response

PS:

Performance status

QOL:

Quality of life

RT:

Radiation therapy

SD:

Stable disease

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Acknowledgements

We thank the Kirin Brewery Co. for providing the clinical grade α-GalCer (KRN7000) for these studies. We thank all the nurses and staff surgeons in the Department of Head and Neck Surgery, Chiba University Hospital, Chiba, Japan, for their valuable technical assistance in the cell culture and for their excellent help with patient care and continuous support. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (Japan; Grants-in-Aid for: Scientific Research in Priority Areas #17016010, Cancer Translational Research Project, The 21st Century Center of Excellence Program), and the Ministry of Health, Labor and Welfare (Japan; Grants-in-aid for Research on Advanced Medical Technology).

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Authors and Affiliations

  1. Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Tetsuro Uchida, Yuriko Tanaka, Heizaburo Yamamoto, Naoki Kunii, Shinichiro Motohashi & Toshinori Nakayama

  2. Department of Otorhinolaryngology and Head and Neck Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Tetsuro Uchida, Shigetoshi Horiguchi, Yuriko Tanaka, Heizaburo Yamamoto, Naoki Kunii & Yoshitaka Okamoto

  3. Laboratory of Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan

    Masaru Taniguchi

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  1. Tetsuro Uchida
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Correspondence to Yoshitaka Okamoto.

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Uchida, T., Horiguchi, S., Tanaka, Y. et al. Phase I study of α-galactosylceramide-pulsed antigen presenting cells administration to the nasal submucosa in unresectable or recurrent head and neck cancer. Cancer Immunol Immunother 57, 337–345 (2008). https://doi.org/10.1007/s00262-007-0373-5

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