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Clinical safety of induced CTL infusion through recombinant adeno-associated virus-transfected dendritic cell vaccination in Chinese cancer patients

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Abstract

Aim

The aim of the study is to explore the safety of cytotoxic T lymphocytes (CTLs) infusion by transfected dendritic cells (DCs) with recombinant adeno-associated virus vector (rAAV) carrying CEA cDNA among advanced cancer patients.

Patients and Methods

A total of 27 cancer patients with tumor tissue expression positivity and/or sera-elevated level of CEA were subsequently divided into cohort A and B resulted from the ex vivo expansion number of CTLs generated from co-culture of specific transfected DCs with autologous T lymphocytes. Based on the variations of infused number of specific CTL derived from different yields of individualized patients who had experienced various anti-cancer treatments, we compared the patients of low number of CTL cells (2–8 × 108 infused, cohort A, 6 cases) with those of higher number (above 8 × 108 infused, cohort B, 21 cases) to testify the possible adverse reactions caused by amount of infused CTLs. This study resembled a phase I study aiming for setting up clinical trial of adoptive cellular therapy that conceptually comes from conventional cytotoxic drugs.

Results

The results showed that one case from the each cohort had experienced moderate fever, and four cases with fatigue were seen in cohort B. The symptoms were transient without serious adverse events. For the consideration of clinical response 2 partial remission (8.0 %, 2/25), 1 minor remission, and 9 stable disease (40 %, 10/25) were observed in 25 patients eligible for evaluation. Sera levels of CEA assay were lowered in six patients. During a median follow-up of 8.1 months, we could not observe severe or chronic adverse reactions related to rAAV-DC infusions. Meanwhile, the variation of number of CTLs infused in this setting did not alter the status of peripheral lymphocyte population.

Conclusions

These preliminary data suggest that the rAAV-DC immunotherapy is well-tolerated and showed no severe adverse reactions in cancer patients.

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Acknowledgments

The authors thank technician Song Wei for her assistant of cytometric analysis. This study is founded by Project 2009CB521700 supported by the National Basic Research Program of China (973 Program) and Capital Development Grant 2007-2053 Beijing.

Conflict of interest

None.

Author information

Author notes

  1. Jun Ren

    Present address: Comprehensive Cancer Center, Medical Oncology and Cancer Immunotherapy Center, Beijing Shijitan Hospital, Capital Medical University, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, China

Authors and Affiliations

  1. Department of Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, China), Peking University School of Oncology/Beijing Cancer Hospital and Institute, 52 Fucheng Rd, Beijing, 100142, China

    Lijun Di, Yulin Zhu, Jun Jia, Jing Yu, Gonghong Song, Jie Zhang, Li Che, Huabing Yang, Yan Han, Bo Ma, Chunrong Zhang, Yanhua Yuan, Miaoning You, Fengling Wan, Xiaoli Wang, Xinna Zhou & Jun Ren

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  1. Lijun Di
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Correspondence to Jun Ren.

Additional information

Lijun Di and Yulin Zhu contributed equally to this article.

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Di, L., Zhu, Y., Jia, J. et al. Clinical safety of induced CTL infusion through recombinant adeno-associated virus-transfected dendritic cell vaccination in Chinese cancer patients. Clin Transl Oncol 14, 675–681 (2012). https://doi.org/10.1007/s12094-012-0854-7

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  • DOI: https://doi.org/10.1007/s12094-012-0854-7

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