Clinical effect of recombinant human interleukin-12 for injection on malignant tumor
WANG Wenqin1, ZHAO Yi2, GONG Xiaojing3, YU Weina3, YANG Lirong3, GAO Lei3, SHEN Hongyu3, WAN Lingqin3, JIA Xifeng3, GUO Na3,and WANG Yishan3
1.Beijing Sanatorium for Retired Cadres, Academy of Military Medical Sciences, Beijing 100039, China; 2.Kang-tai Pharmaceutical Co., Ltd. Qingdao, Qingdao 266001, China; 3.Center of Non-traumatic Treatment and Diagnosis of Tumor, 107 Hospital of PLA, Yantai 264002, China
Abstract：Objective To investigate the effect of rhIL-12 on the hemopoietic function, immune function, radiation protection function and tumor evaluation indexes in the tumor radiotherapy group and advanced palliative treatment group.Methods There were 53 cases of tumor patients treated with Cyber knife in treatment group, including 19 cases of 150 ng/kg, 24 cases of 250 ng/kg, and 10 cases of control. There were 47 cases of cancer patients in advanced palliative treatment group, including 20 cases of 150 ng/kg, 21 cases of 250 ng/kg, and 6 cases of control. rhIL-12 was given on the day of treatment and the therapeutic effect was observed for 4 consecutive weeks. The dose-effect relationship was studied.Results RhIL-12 could significantly inhibit the decline of blood cells, prevent immune disorders and reduce radiation injury in the two groups. After the first-dose, there were 19 cases of fever, 9 cases of discomfor, 2 cases of slight changes in serum aminotransferase and bilirubin. There was no other adverse event.Conclusions rhIL-12 may be a safe and effective drug for cancer prevention and treatment in clinical practice.
Floros T, Tarhini A A. Anticancer cytokines: biology and clinical effects of IFN-γ2, IL-2, IL-15, IL-21, and IL-12[J]. Semin Oncol, 2015, 42(4): 539-548.
Watford W T, Moriguchi M, Morinobu A, et al. The biology of IL-12: coordinating innate and adaptive immune responses[J]. Cytokine Growth Fact Rev, 2003, 14(5): 361-368.
[4]
Dowell A C, Oldham K A, Bhatt R I, et al. Long-term proliferation of functional human NK Cells, with conversion of CD56 (dim) NK cells to a CD56 (bright) phenotype, induced by carcinoma cells co-expressing 4-1BBL and IL-12[J]. Cancer Immunol Immunother, 2012, 61(5): 615-628.
[5]
Smyth M J, Taniguchi M, Street S E. The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent[J]. J Immunol, 2000, 165(5): 2665-2670.
[6]
Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity[J]. Nature Reviews Immunol, 2003, 3(2): 133-146.
[7]
Chen T, Burke K A, Zhan Y, et al. IL-12 facilitates both the recovery of endogenous hematopoiesis and the engraftment of stem cells after ionizing radiation[J]. Exp Hematol, 2007, 35: 203-213.
[8]
Basile L A, Ellefson D, Gluzman-Poltorak Z, et al. HemaMax, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates[J]. PLos One, 2012, 7(2): e30434.
[9]
Gerber S A, Cummings R J, Judge J L, et al. Interleukin-12 preserves the cutaneous physical and immunological barrier after radiation exposure[J]. Radiat Res, 2015,183(1): 72-81.
[10]
Little R F, Aleman K, Kumar P, et al. Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma[J]. Blood, 2007, 110(13): 4165-4171.
[11]
Bekaii-Saab T S, Roda J M, Guenterberg K D, et al. A phase I trial of paclitaxel and trastuzumab in combination with interleukin-12 in patients with HER2/neu-expressing malignancies[J]. Mol Cancer Ther, 2009, 8(11): 2983-2991.
[12]
Lenzi R, Edwards R, June C, et al. Phase II study of intraperitoneal recombinant interleukin-12(rhIL-12) in patients with peritoneal carcinomatosis(residual disease<1 cm) associated with ovarian cancer or primary peritoneal carcinoma[J]. J Transl Med, 2007, 5: 66.
[13]
Lacy M Q, Jacobus S, Blood E A, et al. Phase II study of interleukin-12 for treament of plateau phase multiple myeloma(E1A96): a trial of the Eastern Cooperative Oncology Group[J]. Leuk Res, 2009, 33(11): 1485-1489.
[14]
Gollob J A, Mier J W, Veenstra K,et al.Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN- induction is associated with clinical response[J]. Clin Cancer Res, 2000, 6(5): 1678-1692.
[15]
Carreo V,Zeuzem S,Hopf U,et al.A phase Ⅰ/Ⅱ study of recombinant human interleukin-12 in patients with chronic hepatitis B[J]. J Hepatology, 2000, 32(2): 317-324.
[16]
Jackson J D, Yan Y, Brunda M J, et al. Interleukin-12 enhances peripheral hematopoiesis in vivo[J]. Blood, 1995, 85(9): 2371-2376.
2017, Vol. 28 
