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 John T Kung

Ko Jiunn Liu, Tsu Yi Chao, Jang Yang Chang, Ann Lii Cheng, Hui Ju Ch'Ang, Woei Yau Kao, Yu Chen Wu, Wei Lan Yu, Tsai Rong Chung, Jacqueline Whang-Peng

研究成果: Article

4 引文 (Scopus)

摘要

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 × 106 CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 106 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

原文English
文章編號64
期刊Journal of biomedical science
23
發行號1
DOIs
出版狀態Published - 2016 八月 24

指紋

Tetanus Toxoid
Carcinoembryonic Antigen
Immunotherapy
Dendritic Cells
Interleukin-2
Colorectal Neoplasms
T-cells
Vaccines
Therapeutics
Toxicity
T-Lymphocytes
Chemotherapy
Cell proliferation
Clinical Studies
Blood
Vaccination
Injections
Clinical Protocols

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

引用此文

Liu, Ko Jiunn ; Chao, Tsu Yi ; Chang, Jang Yang ; Cheng, Ann Lii ; Ch'Ang, Hui Ju ; Kao, Woei Yau ; Wu, Yu Chen ; Yu, Wei Lan ; Chung, Tsai Rong ; Whang-Peng, Jacqueline. / 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 John T Kung. 於: Journal of biomedical science. 2016 ; 卷 23, 編號 1.
@article{97e9305060c94c65b60d725e6f3f215c,
title = "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 John T Kung",
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 × 106 CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 106 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",
author = "Liu, {Ko Jiunn} and Chao, {Tsu Yi} and Chang, {Jang Yang} and Cheng, {Ann Lii} and Ch'Ang, {Hui Ju} and Kao, {Woei Yau} and Wu, {Yu Chen} and Yu, {Wei Lan} and Chung, {Tsai Rong} and Jacqueline Whang-Peng",
year = "2016",
month = "8",
day = "24",
doi = "10.1186/s12929-016-0279-7",
language = "English",
volume = "23",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "1",

}

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 John T Kung. / Liu, Ko Jiunn; Chao, Tsu Yi; Chang, Jang Yang; Cheng, Ann Lii; Ch'Ang, Hui Ju; Kao, Woei Yau; Wu, Yu Chen; Yu, Wei Lan; Chung, Tsai Rong; Whang-Peng, Jacqueline.

於: Journal of biomedical science, 卷 23, 編號 1, 64, 24.08.2016.

研究成果: Article

TY - JOUR

T1 - 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 John T Kung

AU - Liu, Ko Jiunn

AU - Chao, Tsu Yi

AU - Chang, Jang Yang

AU - Cheng, Ann Lii

AU - Ch'Ang, Hui Ju

AU - Kao, Woei Yau

AU - Wu, Yu Chen

AU - Yu, Wei Lan

AU - Chung, Tsai Rong

AU - Whang-Peng, Jacqueline

PY - 2016/8/24

Y1 - 2016/8/24

N2 - 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 × 106 CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 106 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

AB - 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 × 106 CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 106 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

UR - http://www.scopus.com/inward/record.url?scp=84983559920&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84983559920&partnerID=8YFLogxK

U2 - 10.1186/s12929-016-0279-7

DO - 10.1186/s12929-016-0279-7

M3 - Article

C2 - 27558635

AN - SCOPUS:84983559920

VL - 23

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

IS - 1

M1 - 64

ER -