Efficient generation of antigen-specific CTLs by the BAFF-activated human B Lymphocytes as APCs: a novel approach for immunotherapy

// Zhang Yiwen 1, 2, 3, * , Gao Shilin 1, 2, 3, * , Chen Yingshi 1, 2, 3 , Su Lishi 1, 2, 3 , Luo Baohong 1, 2, 3 , Liu Chao 1, 2, 3 , Li Linghua 4 , Pan Ting 1, 2, 3 , Zhang Hui 1, 2, 3 1 Institute of Human Virology, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China 2 Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China 3 Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China 4 Department of Infectious Diseases, Guangzhou 8th People’s Hospital, Guangzhou, Guangdong, 510080, China * These authors have contributed equally to this work Correspondence to: Zhang Hui, email: zhangh92@mail.sysu.edu.cn Pan Ting, email: pant8@mail.sysu.edu.cn Keywords: B-lymphocytes, APC, BAFF, HIV-immunotherapy, tumor Received: April 07, 2016 Accepted: October 14, 2016 Published: October 21, 2016 ABSTRACT Efficient antigen presentation is indispensable for cytotoxic T lymphocyte (CTL)-mediated immunotherapy. B-lymphocytes propagated with CD40L have been developed as antigen-presenting cells (APCs), but this capacity needs further optimization. Here, we aimed to expand human B-lymphocytes on a large scale while maintaining their antigen-presenting ability by using both CD40L and B-cell activating factor (BAFF). The addition of BAFF enhanced the expansion efficiency and prolonged the culture time without causing apoptosis of the expanded B-cells. This method thus provided an almost unlimited source of cellular adjuvant to achieve sufficient expansion of CTLs in cases where several rounds of stimulation are required. We also showed that the addition of BAFF significantly enhanced the expression of major costimulatory molecules, CD80 and CD86. Subsequently, the antigen-presenting ability of the B-lymphocytes also increased. Consequently, these B-lymphocytes showed robust CTL responses to inhibit tumor growth after tumor-specific peptide pulses. A similar method induced potent antigen-specific CTL responses, which effectively eradicated human immunodeficiency virus type 1 (HIV-1) latency in CD4 T-lymphocytes isolated from patients receiving suppressive anti-retroviral therapy (ART). Together, our findings indicate that potent antigen-specific CTLs can be generated using BAFF-activated B-lymphocytes as APCs ex vivo. This approach can be applied for CTL-mediated immunotherapy in patients with cancers or chronic viral infections.