The Treatment of Advanced Lung Cancer With Dribbles Antigen by Targeting Activation of Tcells

Malignant tumor has become the leading cause of death in humans, and the number one killer in malignant tumor is the lung cancer. Intensifying environmental pollution comes with rising of the incidence of lung cancer and the high mortality,what's the worst that the 5-year survival rate is only about 15%, accounting for first place in the malignant tumors, Exploiting for novel antitumor technology and products comes to arrest growing attention of the governments and businesses because of the uneffectively curbing of tumor threat to people's life and health on conventional three treatments (surgery, radiotherapy and chemotherapy). Biological and immunotherapy was voted to one of the ten big breakthrough in 2013 by Science magazine, and considered as a new development direction for cancer treatment in the 21st century. The existing immune treatment mainly includes: adoptive immune therapy, tumor vaccine therapy, immune checkpoint-antibody therapy and other auxiliary therapy, and the adoptive immunotherapy was researched and developeded former in addition the most mature treatment among these therapies. Recently, Dr Hu Hong - Ming's team put forward an innovative cancer treatment strategy: using of autophagy role to capture tumor antigen for preparation of tumor vaccine. In this strategy, the blocking proteasome activity of in vitro cultured tumor cells dealed with Bortezomib (proteasome inhibitors) causes enrichment of short-lived protein (SLiPs) and misfolded proteins (DRiPs) in autophagosome,called DRibbles corpuscle. Tumor vaccine maded from collecting these DRibbles corpuscle preparation as, also known as the DRibble vaccine. At present, clinical research has been carried out about Dribble liver cancer vaccine unit with DC - CIK therapy in liver cancer in the second hospital of Nanjing nearly four years,and more than 300 cases has been completed. Clinical research results show that Dribble vaccine has good security, producing stronger immune response compared with the DC-CIK therapy alone. But it is still no cognization for the efficacy and safety of DC-CIK joint DRibble lung cancer vaccine in China, whether it is better than the current DC - CIK immune therapy, needed for further clinical research and expected to provide a better immune treatment for NSCLC patients.

Sex

All

Minimum age

18 Years

Maximum age

80 Years

Inclusion Criteria:

* Aged 18-80 years old, pathological diagnosis of advanced non-small cell lung cancer, after treatment with radiation and chemotherapy and (or) targeted drugs disease still progress.
* Clear that heart, lung, liver, kidney at physical basic normal, and basic normal immune system function.
* No allergic reaction of biological products, asthma and other allergic constitution.
* A patient or his legal representative signed informed consent.

Exclusion Criteria:

* The obvious blood coagulation dysfunction patients.
* Patients infected with tuberculosis, hepatitis b, AIDS and syphilis positive diseases.
* Severe diabetes, high blood pressure, stroke, heart failure, and kidney disease.
* Autoimmune diseases such as systemic lupus erythematosus (sle) and Rheumatoid arthritis (ra)
* Large doses or long-term glucocorticoid, and other immunosuppressive users (more than 4 weeks).
* Pregnant and nursing women has a history of allergies of biological products.
* Collect blood and doping in another place.
* Allergies or active infection that effect the observation of Tolerance activity.
* Heart, lung, liver, kidney or bone marrow function obviously low.
* Unable or unwilling to sign a consent form or to comply with the technical requirement.

• BACKGROUNDXue M, Fan F, Ding L, Liu J, Su S, Yin P, Cao M, Zhao W, Hu HM, Wang L. An autophagosome-based therapeutic vaccine for HBV infection: a preclinical evaluation. J Transl Med. 2014 Dec 20;12:361. doi: 10.1186/s12967-014-0361-4. PMID 25526800
• BACKGROUNDZhou M, Li W, Wen Z, Sheng Y, Ren H, Dong H, Cao M, Hu HM, Wang LX. Macrophages enhance tumor-derived autophagosomes (DRibbles)-induced B cells activation by TLR4/MyD88 and CD40/CD40L. Exp Cell Res. 2015 Feb 15;331(2):320-30. doi: 10.1016/j.yexcr.2014.10.015. Epub 2014 Oct 24. PMID 25447440
• BACKGROUNDRen H, Zhao S, Li W, Dong H, Zhou M, Cao M, Hu HM, Wang LX. Therapeutic antitumor efficacy of B cells loaded with tumor-derived autophagasomes vaccine (DRibbles). J Immunother. 2014 Oct;37(8):383-93. doi: 10.1097/CJI.0000000000000051. PMID 25198526
• BACKGROUNDYe W, Xing Y, Paustian C, van de Ven R, Moudgil T, Hilton TL, Fox BA, Urba WJ, Zhao W, Hu HM. Cross-presentation of viral antigens in dribbles leads to efficient activation of virus-specific human memory T cells. J Transl Med. 2014 Apr 16;12:100. doi: 10.1186/1479-5876-12-100. PMID 24735498