Format

Send to

Choose Destination
J Biomed Sci. 2016 Aug 24;23(1):64. doi: 10.1186/s12929-016-0279-7.

A phase I clinical study of immunotherapy for advanced colorectal cancers using carcinoembryonic antigen-pulsed dendritic cells mixed with tetanus toxoid and subsequent IL-2 treatment.

Author information

1
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan. kojiunn@nhri.org.tw.
2
Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan. kojiunn@nhri.org.tw.
3
School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan. kojiunn@nhri.org.tw.
4
Division of Hematology/Oncology, Tri-Service General Hospital, Taipei, Taiwan.
5
Present Address: Department of Hematology/Oncology, Taipei Medical University Shuang Ho Hospital, Taipei, Taiwan.
6
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
7
Present Address: Division of Hematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
8
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
9
Present Address: Division of Hematology-Oncology, Department of Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan.
10
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan. jqwpeng@nhri.org.tw.
11
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. jqwpeng@nhri.org.tw.
12
Present Address: Comprehensive Cancer Center, Taipei Medical University, Taipei, Taiwan. jqwpeng@nhri.org.tw.

Abstract

BACKGROUND:

To better evaluate and improve the efficacy of dendritic cell (DC)-based cancer immunotherapy, we conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen (CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in the vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine efficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of vaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment.

METHODS:

Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic colorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic colorectal cancer with 1 × 10(6) CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 10(6) CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the final DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical status. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation responses against CEA.

RESULTS:

No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC vaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically significant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients.

CONCLUSIONS:

The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this protocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of patients. This treatment protocol should be further evaluated in additional colorectal cancer patients with modifications to enhance T cell responses.

TRIAL REGISTRATION:

ClinicalTrials.gov (identifier NCT00154713 ), September 8, 2005.

KEYWORDS:

Carcinoembryonic antigen; Colorectal cancer; Dendritic cell; Interleukin-2; Tetanus toxoid

PMID:
27558635
PMCID:
PMC4997699
DOI:
10.1186/s12929-016-0279-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center