Immunotherapy

CAR-T therapy, as one of various strategies for adoptive immunotherapy has received considerable attentions. It plays a critical role in personalized and precision medicines in advancement of clinical performance for cancer patients.
Patient’s T cells are acquired from apheresis, when genetically modified, massively expanded, and infused into the patient, these T-cells can specifically target tumor associated antigen (TAA) and eradicate them.

Hepatocellular carcinoma (HCC) is the fifth most common cancer with over 500000 new cases diagnosed per year and the third most common cancer mortality with annual death rate of 250000 people worldwide [1]. Although surgery is the most effective treatment for HCC, tumor recurrence is very high, and the 5-year survival rate remains at only 10% [2]. Moreover, because the majority of patients with HCC are diagnosed at advanced stage, potentially curative therapies, including chemotherapy, chemoembolization, are frequently ineffective. Sorafenib (Nexavar), the first clinically approved targeted drug therapy for HCC, could only prolong the overall survival by 2-3 months [3] and many patients must withdraw from treatment due to severe skin toxicity [4]. Thus, it remains an urgent need for tolerable, life-extending strategies in the management of HCC patients.
Clinical Trial
Reference:
1]  El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557-76.
2]  Altekruse SF, McGlynn KA, and Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 2009;27:1485-1491.
3]  Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359:378-390.
4]  Strumberg D, Richly H, Hilger RA, Schleucher N, Korfee S, Tewes M, et al. Phase I clinical and pharmacokinetic study of the novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol 2005;23:965-972.008; 359:378-390.
Glioblastoma (GBM) is the most common and malignant subtype of primary brain tumors and accounts for 54.4% of primary brain and CNS gliomas[1]. GBM exhibits an extremely aggressive biological behavior and progressively invades wide areas of the brain parenchyma [2]. The current standard therapy combines maximal surgical resection, followed by radiotherapy with concomitant and adjuvant temozolomide [3]. Despite this multimodal approach, median survival is limited to 16 to 19 months, with approximately 25% to 30% of the patients survive at 2 years after diagnosis [3-5].
Clinical Trial
Reference:
1]    Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C and Barnholtz-Sloan JS. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol. 2013; 15 Suppl 2:i1-i56.
2]  Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK and DePinho RA. Malignant glioma: genetics and biology of a grave matter. Genes Dev. 2001; 15(11):1311-1333.
3]  Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A and Lacombe D, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352(10):987-996.
4]  Omuro A and DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA. 2013; 310(17):1842-1850.
5]  Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Jaeckle KA, Armstrong TS, Wefel JS, Won M, Blumenthal DT, Mahajan A, Schultz CJ, Erridge S, Baumert B, Hopkins KI and Tzuk-Shina T, et al. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J CLIN ONCOL. 2013; 31(32):4085-4091.
Lung cancer ranks no.1 among all malignant tumors in terms of incidence and mortality rates[1,2]It is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), accounting for about 87% and 13% of all cases, respectively. Lung squamous cell carcinoma (LSCC) (30–35%), adenocarcinoma (LAD) (50–60%), and large cell carcinoma (5–10%) are the most common histologic subtypes of NSCLC [3,4]There are very limited effective treatment strategies for LSCC. Before 2015, targeted agents have not yet been developed for LSCC and chemotherapy continues to be the standard treatment[5,6]Fortunately, nivolumab, a programmed death 1 (PD-1) immune checkpoint inhibitor, has been approved this year for the treatment of LSCC in the second-line setting[7]However, the overall response ratio of nivolumab is just about 15%. Thus, novel treatment strategies are still urgently needed for patients with LSCC.
Reference
1]  Yalman, D., Neoadjuvant radiotherapy/chemoradiotherapy in locally advanced non-small cell lung cancer. Balkan Med J, 2015. 32(1): p. 1-7.
2]  Uzel, E.K. and U. Abacioglu, Treatment of early stage non-small cell lung cancer: surgery or stereotactic ablative radiotherapy? Balkan Med J, 2015. 32(1): p. 8-16.
3]  Whithaus, K., et al., Evaluation of napsin A, cytokeratin 5/6, p63, and thyroid transcription factor 1 in adenocarcinoma versus squamous cell carcinoma of the lung. Arch Pathol Lab Med, 2012. 136(2): p. 155-62.
4]  Chen, G. and X.H. Yi, [Pathology and genetics of disease and tumours of the lung, pleura in China]. Zhonghua Bing Li Xue Za Zhi, 2005. 34(8): p. 490-3.
5] Scagliotti, G.V., et al., Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol, 2008. 26(21): p. 3543-51.
6]  Tiseo, M., et al., FGFR as potential target in the treatment of squamous non small cell lung cancer. Cancer Treat Rev, 2015.
7] Ang, Y.L., H.L. Tan, and R.A. Soo, Best practice in the treatment of advanced squamous cell lung cancer. Ther Adv Respir Dis, 2015.