|
|
Experimental study on anti- ovarian carcinoma effect of minicircle DNA expressing anti-EpCAM/anti-CD3 bispecific BiTE in vitro |
CHEN Yuanqun1 CHEN Ping2 CHEN Guochuang2 WEI Zhihong3 |
1.Department of Gynecology, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People′s Hospital, Guangdong Province, Shenzhen 518035, China;
2.Shenzhen Advanced Technology Research Institute, Chinese Academy of Sciences, Guangdong Province, Shenzhen 518055, China;
3.Department of Gynecology, Shenzhen Bao′an People′s Hospital (formerly belonged to Affiliated Hospital of Shenzhen University, Shenzhen Second People′s Hospital), Guangdong Province, Shenzhen 518101, China |
|
|
Abstract Objective To study the effect of anti-EpCAM/anti-CD3 BsAb protein inhibition on ovarian cancer cells in vitro. Methods Non-viral vector microcircle DNA was used to obtain the anti-EpCAM/anti-CD3 BsAb protein. Different concentrations (1×10-3, 1×10-4, 1×10-5, 1×10-6, 1×10-7, 1×10-8 μg/mL) of anti-EpCAM/anti-CD3 BsAb protein was added to ovarian cancer cells and T cells. After 6 h and 12 h, the number of live cells and dead cells were counted and morphological changes were observed by inverted fluorescence microscopy. Results Under the inverted microscope, ovarian cancer cells and T cells were obviously aggregated after the addition of anti-EpCAM/anti-CD3 BsAb, and a large number of dead cells were found around them. At the same time, the killing effect of ovarian cancer cells mediated by T cells did not always increased with the increase of concentration. When the concentration reached 1×10-4 μg/mL, the killing rate reached the maximum in both 6 h and 12 h time periods, and the difference were both statistically significant (P < 0.05). Conclusion The anti-EpCAM/anti-CD3 BsAb expressed by the novel microcircle DNA expression system can inhibit the growth of ovarian cancer cells in vitro, and it may be used as an effective targeted anti-ovarian cancer tumor in the future.
|
|
|
|
|
[1] Brawley OW. Ovarian cancer prevention:Time for primetime? [J]. Cancer,2015,121(13):2121-2123.
[2] Abiko K,Matsumura N,Hamanishi J,et al. IFN from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer [J]. Brit J Cancer,2015,112(9):1501-1509.
[3] Marth C,Vergote I,Scambia G,et al. ENGOT-ov-6/TRINOVA-2:Randomised,double-blind,phase 3 sudy of pegylated liposomal doxorubicin plus trebanannib or placebo in women with recurrent partially platinumisensitive or resisitant ovarian cancer [J]. Eur J Cancer,2017,70:111-121.
[4] Swisher EM,Lin KK,Oza AM,et al. Rucaparib in relapsed,platinum-sensitive high-grade ovarian carcinoma [J]. Lancet Oncol,2017,18(1):75-87.
[5] 刘继红,黄绮丹.复发性卵巢癌的靶向治疗[J].实用妇产科杂志,2017,33(11):809-812.
[6] 李梦娇,李浩然,程玺,等.靶向治疗药物相关标志物在卵巢透明细胞癌组织中的表达及其临床意义[J].中华妇产科杂志,2017,52(12):835-843.
[7] Shashati A. Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling [J]. J Pathol,2013,231(1):21-34.
[8] Yu S,Li A,Liu Q,et al. Recent advances of bispecific antibodies in solid tumors [J]. J Hematol Oncol,2017,10(1):155.
[9] Grugan KD,Dorn K,Jarantow SW,et al. Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells [J]. MAbs,2017,9(1):114-126.
[10] Yu S,Li A,Liu Q,et al. Chimeric antigen receptor T cells:a novel therapy for solid tumors [J]. J Hematol Oncol,2017,10(1):78.
[11] Li YL,Ye F,Hu Y,et al. Identification of suitable reference genes for gene expression studies of human serous ovarian cancer by realtime polymerase chain reaction [J]. Arch Virol,2016,394(3):110-116.
[12] Patch AM,Christie EL,Etemadmoghadam D,et al. Whole-genome characterization of chemoresistant ovarian cancer [J]. Nature,2015,521(7553):489-494.
[13] Kantarjian H,Stein A,Gokbuget N,et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia [J]. N Engl J Med,2017,376(9):836-847.
[14] Coleman RL,Brady MF,Herzog TJ,et al. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent,platinum-sensitive ovarian cancer [J]. Lancet Oncol,2017,18(6):779-791.
[15] Sharpe AH. Introduction to checkpoint inhibitors and cancer immunotherapy introduction [J]. Immunol Rev,2017,276(1):5-8.
[16] Gill S,Maus MV,Porter DL. Chimeric antigen receptor T cell therapy:25years in the making [J]. Blood Rev,2016, 30(3):157-167.
[17] Kay MA,He CY,Chen ZY. A robust system for production of minicircle DNA vectors [J]. Nat Biotechnol,2010, 28(12):1287-1289.
[18] 戴岚,刘艺璇,谢蕾,等.抑制S1PR2蛋白表达对卵巢上皮性癌SKOV3细胞增殖能力的影响[J].中华妇产科杂志,2018,53(2):106-110.
[19] Lamers CHJ,Willemsen R,Van Elzakker P,et al. Immune responses to transgene and retroviral vector in patients treated with ex vivo-engineered T cells [J]. Blood,2011,117(1):72-82.
[20] Huehls AM,Coupet TA,Sentman CL. Bispecific T cell engagers for cancer immunotherapy [J]. Immunol Cell Biol,2015,93(3):290-296. |
|
|
|