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건강 100세의 꿈을 이룰 의학혁명의 열쇠 新 개별화 의료

*제목 Anti-tumor effect of dendritic cell-based immunotherapy in combination with chemotherapy in the patients with advanced colorectal cancer.

010/04/21

Shinichiro Akiyama1, Jun Tsukada2, Takeshi Tomoda3, Hiroyuki Abe1, Masato Okamoto4.

1Kudan Clinic, Tokyo, Japan; 2tella, Inc., Tokyo, Japan; 3Seren Clinic, Tokyo, Japan; 4Musashino Univ., Tokyo, Japan

Abstract

Background and objective: Tumor-specific cytotoxic T lymphocytes (CTLs) can be activated in vivo by dendritic cell (DC)-based

vaccination.

However, clinical responses to the immunotherapy with DC vaccination have only been observed in a minority of patients with

solid cancer. Combination with other treatment modalities such as chemotherapy may overcome immunoresistance of cancer cells.

In the current study, the clinical efficacy of the DC vaccine pulsed with the peptide derived from colorectal cancer-associated

antigens in combination with chemotherapy has been evaluated in the patients with advanced, inoperable colorectal cancer.

Patients and Methods: Thirty-two patients with advanced, inoperable colorectal cancer refractory to standard treatment were

entered the study.

DCs which were generated from CD14+ monocytes from leukapheresis by 6-day cultivation with granulocyte macrophage-colony

stimulating factor (GM-CSF) and interleukin (IL)-4, were matured by OK-432, a streptococcal agent, and were pulsed with the

pancreatic cancer-associated antigens, such as WT1, MUC1. These DCs (1 x 107) were intradermally administered 5 times at

14-day intervals.


Results:
Of the 32 patients, complete response (CR) was observed in 0 (0%), partial response (PR) in 7 (21.9%), stable disease (SD)

in 12 (37.5%), progressive disease (PD) in 13 (40.6%). Response rate was 21.9%. Tumor control rate was 59.4%. Survival rate,

quality of life, performance status were markedly increased. Severe side effects of more than grade 3 which were assessed in

accordance with NCI-Common Toxicity Criteria v.2.0, were not observed.


Conclusions:

It was strongly suggested that the DC vaccination pulsed with cancer associated-peptides in combination with chemotherapy

was safety and effective in the patients with the inoperable colorectal cancer refractory to standard treatment.


*2010, 101회 미국 암학회
April 17-21, 2010 Washington DC, U.S.A