On 3rd October, 2011, the Canadian scientist, member of Institute of Medicine and National Academy of Science in the US, Professor Ralph M. Steinman, was awarded as one of the Nobel Laureates in Medicine according to the “Discovery of the Dendritic cell (DC cell) and its role in the adaptive immune system”. In the early 21st century, under the supervision of Professor Steinman in Stanford Cancer Institute in the US, Professor Yong LIU combined his research in Recombinant Adeno-associated Virus (rAAV) with the work of Professor Steinman to develop a type of rAAV transfected DC cells which could carry one or several type of tumor-associated epitopes determinant gene(s). By in vitro elicitation of T lymphocytes from patients, cytotoxic T lymphocytes (CTL) would be generated to target specific anti-tumor related antigen positive cancer cells. With subsequent related clinical research, such technology, which was named as “AAV-DC-CTL Tumor Cell Targeting Therapy Technology”, was proven to be successful and has obtained protection from 5 international patents. The cytotoxic T lymphocytes (A-CTL, in which A represents specific antigen) generated by this technology possess powerful function which can efficiently and specifically eliminate one or several type of specific tumor-related antigen positive cancer cells and PSMA positive angiogenesis tumor endothelial cells. Nevertheless, there is no harm to any normal cells.
The typical examples of clinical application of AAV-DC-CTL Tumor Cell Targeting Therapy Technology have been revealed by Professor Steinman and the late CEO of Apple Computer, Steve Jobs, during their advanced phase of pancreatic cancer. By applying this therapeutic technology, the lifespan of Professor Steinman was extended by 4 years. Together with the application with other treatments, Steve Jobs could survive for 6 more years.
After performing the clinical research in Stanford Cancer Institute for several years, by 2010, it was proven that besides direct targeting elimination of cancer cells, A-CTL specific cytotoxic T lymphocytes could also block blood vessels produced by tumor angiogenesis, facilitating indirect anti-cancer effect and enhancing clinical efficacy significantly. Such research outcome was commented as the most important breakthrough in cancer biotherapy by the American Society of Clinical Oncology (ASCO) in the first half of 2010.
The clinical research in the US showed that A-CTL specific cytotoxic T lymphocytes not only possibly reverse the drug-resistance of gynecological and prostate gland cancers due to hormonal therapy, but also probably reverse the resistance of cancer cells against other molecular targeted drugs, including IRESSA and Avastin. As such, Professor Liu was rewarded research funding from Roche USA to perform the related research work.
According to the estimation from International Agency for Research on Cancer (IARC), cancer incidence rate will increase by 3-5% annually in the future. By 2020, there would be 20 millions of new cases. Meanwhile, death cases would reach 12 millions. In China, the occurrence of cancer is showing a rapid growth obviously. Due to the serious toxic side-effects of traditional radiochemotherapy, the quality of life of cancer patients is greatly demolished. Furthermore, experimental results show that only old and weak cancer cells can be eliminated by radiochemotherapy. In addition, the problems of metastasis and drug-resistance still cannot be avoided. Although molecular targeted drugs possess the characteristic of high specificity to cancer cells and the quality of life of patients can be well improved, the shortcoming is that after applying molecular targeted drugs for a certain time frame, cancer cells would undergo mutational pathways to develop drug resistance. Since the new “people-oriented” concept in medical treatment development has been widely accepted, the promotion of clinical use of AAV-DC-CTL Tumor Cell Targeting therapy can facilitate high specificity cancer cell elimination, low or even no toxic side-effects, without drug resistance, higher chance of recovery, greater improvement in the quality of life of patients at advanced stage of cancer, and the possibility of cancer patients having good quality of living and working life even living along with tumors for long time. Therefore, AAV-DC-CTL Tumor Cell Targeting Therapy technology offers cancer patients not only an improved therapeutic method, but also a huge leap in the overall concept of cancer treatment.
AAV-DC-CTL Tumor Cell Targeting therapy belongs to the aspect of cancer biotherapy technology. In 2000, the report of the annual meeting of “International cancer bio-/immunotherapy and gene therapy” concluded that “Biotherapy is currently known as the only possible mean to eliminate cancer completely. The 21st century would be the era of cancer biotherapy.” However, nowadays, due to the uncertainty in efficacy and the greater side-effects in the use of LAK cell, CIK cells, DC cell immunotherapy, cancer biotherapy cannot gain wide recognition by specialists in oncology. Thus, cancer biotherapy can only work as an adjuvant therapy. Generated by AAV-DC-CTL Tumor Cell Targeting therapy technology, A-CTL specific cytotoxic T lymphocytes obtained possess precise clinical efficacy and ratable characteristics. With the in-depth clinical application research and recruitment of larger sample pools in multiple clinical trial centers, more significant and complementary scientific data can be obtained. It is expected that the launching of AAV-DC-CTLTM Tumor Cell Targeting therapy would make cancer biotherapy become the 4th practical cancer treatment after surgery, radiotherapy and chemotherapy, implying tremendous clinical and academic significance.