Effective adoptive transfer of haploidentical tumor-specific T cells in B 16-melanoma bearing mice

• Published in: 中华医学杂志（英文版） Vol. 125; no. 5; pp. 794 - 800
• Main Authors: CUI Nai-peng, XIE Shao-jian, HAN Jin-sheng, MA Zhen-feng, CHEN Bao-ping, CAI Jian-hui
• Format: Journal Article
• Language: English
• Published: Department of Gastrointestinal Surgery, Department of Oncology & Immunotherapy, Hebei General Hospital, Shijiazhuang, Hebei 050051, China 2012; Department of Surgery, Hebei Medical University, Shijiazhuang,Hebei 050017, China%Department of Oncology & Immunotherapy, Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China%Department of Surgical Oncology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, China%Department of Surgery, Hebei Medical University, Shijiazhuang,Hebei 050017, China
• Subjects: B16 melanoma; adoptive transfer; tumor microenvironment; adoptive immunotherapy; graft-versus-host disease
• ISSN: 0366-6999
• DOI: 10.3760/cma.j.issn.0366-6999.2012.05.013

R2; Background Adoptive transfer of allogeneic tumor-specific T cells often results in severe graft-versus-host disease (GVHD).Here,we sought to maximize graft-versus-tumor and minimize GVHD by using haploidentical T cells in pre-irradiated B16-melanoma bearing mice.Methods C57BL/6 mice bearing B16-melanoma tumors were irradiated with 0,5,or 7 Gy total body irradiation (TBI),or 7 Gy TBI plus bone marrow transplantation.Tumor areas were measured every 3 days to assess the influence of irradiation treatment on tumor regression.B16-melanoma bearing mice were irradiated with 7 Gy TBI; sera and spleens were harvested at days 1,3,5,7,9,11,and 13 after irradiation.White blood cell levels were measured and transforming growth factor β1 (TGF-β1) and interleukin 10 (IL-10) levels in serum were detected using enzyme-linked immunosorbent assay (ELISA) kits.Real-time reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry were performed to test TGF-β1,IL-10 and Foxp3 mRNA levels and the proportion of CD4+CD25+Foxp3+ T-regulatory cells (Tregs) in spleens.B16-melanoma bearing C57BL/6 mice were irradiated with 7 Gy TBI followed by syngeneic (Syn1/Syn2) or haploidentical (Hap1/Hap2),dendritic cell-induced cytotoxic T lymphocytes (DC-CTLs) treatment,tumor areas and system GVHD were observed every 3 days.Mice were killed 21 days after the DC-CTLs adoptive transfer;histologic analyses of eyes,skin,liver,lungs,and intestine were then performed.Results Irradiation with 7 Gy TBI on the B16-melanoma-bearing mice did not influence tumor regression compared to the control group; however,it down-regulated the proportion of Tregs in spleens and the TGF-β1 and IL-10 levels in sera and spleens,suggesting inhibition of autoimmunity and intervention of tumor microenvironment.Adoptive transfer of haploidentical DC-CTLs significantly inhibited B16-melanoma growth.GVHD assessment and histology analysis showed no significant difference among the groups.Conclusion Adoptive transfer of haploidentical tumor-specific T cells in irradiation-pretreated B16-melanoma bearing mice preserved antitumor capacity without causing a GVHD response.