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Pancreatic carcinoma-specific immunotherapy using synthesised alpha-galactosyl epitope-activated immune responders: findings from a pilot study

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International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Dendritic cell (DC)-based and cytokine-induced killer cell (CIK)-based therapy can induce specific antitumor T-cell responses. This clinical pilot study examined the safety, the feasibility, and the outcome of tumor-specific immunotherapy for patients with advanced pancreatic adenocarcinoma.

Methods

Alpha-Gal epitopes were synthesised on pancreatic carcinoma cell membranes with α1,3-galactosyltransferase in vitro. Subsequently, the addition of natural human anti-Gal IgG to the processed membranes resulted in opsonization and effective phagocytosis by DCs, which were co-cultured with newly differentiated CIKs from bone marrow stem cells to generate tumor-specific immune responders ex vivo. Fourteen patients with inoperable stage III/IV pancreatic adenocarcinoma were enrolled in the study; the treatment procedure consisted of injections of DCs and CIKs.

Results

Clinical observation showed that the procedure was safe and lacked serious side effects. Tests showed that 12 patients had strong positive delayed-type IV hypersensitivity to the autologous cancer cell lysate; robust systemic cytotoxicity elicited by interferon (IFN)γ expression by peripheral blood mononuclear cells; and significant increases in CD3+CD8+, CD3+CD45RO+, and CD3+CD56+ cells in peripheral blood lymphocytes after 3 injections. During the follow up, the percentages of CD3+CD8+, CD3+CD45RO+, and CD3+CD56+ cells returned to the normal range at 6 to 9 months after the third injection and IFNγ expression in the cells stayed at the higher level from the third injection to 24 months after the treatment.

Conclusions

This new tumor-specific immunotherapy is safe, feasible, and has great potential for pancreatic carcinoma treatment.

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Acknowledgments

This work was supported by the Hong Kong Wang Kuan Cheng Grant and Inner Mongolia Stem Cell Grant (Grant code: kjk10jhg). We also thank Professor Jin Gao, who processed the α-1,3-Gal epitope-pulsed DCs and CIKs at the Jing Meng Stem Cell Company, Beijing, China.

Conflict of interest

All authors declared that they had no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Oncology, First Teaching Hospital, Inner Mongolia Medical College, Huhhot, China

    Ying Qiu & Sheng Yun

  2. Medical School, University College London, London, UK

    Mark M. Yun

  3. The Armed Police General Hospital, Beijing, China

    Ming Bao Xu

  4. Aerospace Medical College, Peking University, Beijing, China

    Yi Zhong Wang

  5. Clinical Sciences Centre, MRC, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK

    Sheng Yun

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  1. Ying Qiu
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  2. Mark M. Yun
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  3. Ming Bao Xu
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Corresponding author

Correspondence to Sheng Yun.

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Qiu, Y., Yun, M.M., Xu, M.B. et al. Pancreatic carcinoma-specific immunotherapy using synthesised alpha-galactosyl epitope-activated immune responders: findings from a pilot study. Int J Clin Oncol 18, 657–665 (2013). https://doi.org/10.1007/s10147-012-0434-4

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  • DOI: https://doi.org/10.1007/s10147-012-0434-4

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