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

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.

• Authors: Ying Qiu, Mark M Yun, Ming Bao Xu, Yi Zhong Wang, Sheng Yun
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 18 Issue 4 Pg. 657-65 (Aug 2013) ISSN: 1437-7772 [Electronic] Japan
• PMID: 22847800 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD3 Complex
• CD56 Antigen
• NCAM1 protein, human
• Trisaccharides
• alpha-galactosyl epitope
• Interferon-gamma
• Leukocyte Common Antigens

Topics

• Adult
• Aged
• Aged, 80 and over
• CD3 Complex (metabolism)
• CD56 Antigen (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Transplantation (methods)
• Coculture Techniques
• Cytokine-Induced Killer Cells (immunology)
• Dendritic Cells (immunology)
• Female
• Hematopoietic Stem Cells (immunology)
• Humans
• Immunotherapy (methods)
• Interferon-gamma (immunology, metabolism)
• Leukocyte Common Antigens (immunology, metabolism)
• Male
• Middle Aged
• Pancreatic Neoplasms (immunology, pathology, therapy)
• Pilot Projects
• Treatment Outcome
• Trisaccharides (chemical synthesis, immunology)