Zhou Guoying: a new generation of oncolytic virus therapy leader!

Introduction: an exclusive interview with Zhou Guoying, a scientist who is deeply involved in herpes virus, CEO of Yinuowei and President of the Research Institute< br / > < br / > < br / > in 2015, the U.SFDA approved the listing of t-vec, which ushered in a new turning point for tumor treatment and even biomedical industrySince then, more people have heard the stories of "oncolytic virus" and "Zhou Guoying" for the first time< br / > in this new battlefield, if Zhou Guoying didn't launch the "first shot", then she must be able to play the role of "blowing the charge"Zhou Guoying is regarded as the founder of the oncolytic virus by his international colleagues because of his initiative in tumor targeted gene therapy of oncolytic herpesvirusEven the R & D of t-vec is based on the original framework of Zhou Guoying's teamIn 2015, Zhou Guoying led the establishment of Shenzhen rozeman International Institute of translational medicine, aiming at the combination and transformation of production, learning and research of biological medicine in Dawan districtBy the end of 2019, the biological medicine base in the bay area of rozeman was officially opened< br / > why is oncolytic virus a product of "accidental" discovery? Will this mechanism change the human anti-tumor situation? What else can we do in cancer therapy? What projects have Shenzhen rozeman International Institute of translational medicine introduced since its establishment? For Yinuowei, how can we make the latecomers stay on top? What are the possibilities of biomedicine in Dawan district? With these problems in mind, Wan District freehand interviewed Zhou Guoying, a scientist who is deeply involved in herpes virus, CEO of innova and President of the Research Institute< br / > encounter oncolytic virus < br / > Q < br / > as an internationally recognized important founder of tumor immunotherapy targeted by herpes simplex virus (HSV), what were the opportunities and reasons for you to work in this direction? < br / > Zhou < br / > no matter in Shanghai Institute of Biochemistry, Chinese Academy of Sciences, or later to the University of Chicago, I have been doing research in the field of virus, but the subdivision direction is gradually changing from the beginning of plant virus and animal virus to medical virus< br / > in the field of virus, the common problem to be solved is whether there is vaccine or antibodyTherefore, the research needs to focus on the relationship between virus and hostBut here's a remarkable phenomenon: when the virus comes, it's not so easy to follow the path of developing vaccines or antibodies - you'll find that there's little chance of success in making vaccines or antibody drugs in the field of Virology< br / > but even so, we have done several decades of research in the past and got the results about the relationship between virus and host, which is actually very meaningfulBesides publishing papers, is it helpful for the transformation of achievements? It is because of decades of scientific research accumulation that we found oncolytic virus< br / > our initial goal was not to develop oncolytic viruses, but to study the interaction between viruses and their hostsThis process has accumulated a lot of scientific discoveries and hundreds of various recombinant viruses, and oncolytic virus is just one of themIn 1990, it was found that the replication ability of the recombinant virus in normal cells was very low, but it could be very active in tumor cells, which inspired us to think about the feasibility of using virus to fight tumor< br / > ask < br / > is there any bottleneck at that time? For example, HSV is one of the most vulnerable viruses, and it lurks for lifeHow to ensure its safety? < br / > week < br / > from the first discovery of herpes virus in 1990 to t-vec officially approved by FDA in 2015, it can be used as oncolytic virus for tumor treatment after recombination and transformationPeople who have been doing basic theoretical research all their lives are actually hard to think about the transformation of achievements from the perspective of industrializationTheir ideas and ideas are totally differentTherefore, the original patent articles on oncolytic virus and other achievements do not have drug-forming properties< br / > first of all, as a drug, safety is the most important factorWhether it's oncolytic virus or other drugs, it's necessary to take into account that this drug must be used by patients in the futureSo as a oncolytic virus, a living virus, would the patient like to use it? Will doctors, nurses and patients be infected? What are the consequences of infection? In addition to safety, there is also an ethical issue, which has become a major obstacle to the development of oncolytic viruses for many years< br / > so back again, we pay attention to selecting virusesWe must choose some very safe virusesThe so-called "safety" means that even if it's a wild virus, if I don't make any changes to it, it's relatively safeFrom this point of view, HSV-1 is exactly what we want< br / > epidemiological survey shows that the proportion of herpes simplex virus-1 (HSV-1) infection in American adults is 50% - 80%Although it is latent for life, in most cases, the result of the virus attack is only herpes on the lips Such a virus is relatively safe in itself, and its side effects are even lower after it is recombined and edited In terms of safety, HSV-1 is recognized as the safest oncolytic virus in the world < br / > as for using other viruses, it is the same Through the transformation to make it more safe, this is our reasonable way to treat oncolytic virus, not to stop eating because of choking < br / > one shot of "cardiotonic" < br / > Q < br / >: in 2015, oncolytic virus t-vec was approved by FDA and then widely used; however, in 2005, the market feedback of recombinant human adenovirus 5 injection (ankeri) approved by China was poor What do you think of these two nodes? What do you think are the factors that have contributed to the success of Arcturian in the market? < br / > week < br / > at that time, oncolytic virus, as an anticancer drug, faced several challenges: first, whether neutralizing antibody will be produced soon after virus injection and weaken the drug; second, it was related to the domestic drug registration and supervision environment at that time, and experts and clinicians' research and understanding of oncolytic virus were not consistent as a whole; third, the hospital and patients' acceptance of injected virus mentioned above, It also has a certain impact < br / > so looking back to October 2015, FDA took the lead in approving t-vec to go on the market, which gave a shot of "heart tonic" to the drug development of oncolytic virus Since then, there have been more and more oncolytic virus projects around the world, and the industry has gradually deepened its understanding < br / > Q < br / > oncolytic virus therapy can be injected intravenously or intratumorally; it can not only target primary tumors, but also control metastatic tumors But at present, oncolytic virus is mainly injected into tumor, and the field of treatment is limited What is the difficulty of breakthrough? < br / > week < br / > from the characteristics of oncolytic virus, its replication ability in tumor cells is very strong, which is very suitable for intratumoral injection On the other hand, oncolytic virus does not grow eyes Although the replication ability of oncolytic virus is very low after entering normal cells, it will also have certain micro environmental impact, such as cytokine storm, etc., which makes it safer to limit these side effects in tumor cells < br / > in addition, intravenous injection of oncolytic virus will easily produce neutralizing antibody, which will affect the subsequent efficacy On the contrary, intratumoral injection can not only avoid the problems of drug resistance, but also stimulate the immune response of tumor microenvironment, and focus on the fire to eliminate the tumor quickly < br / > but the problem also comes: for those advanced tumors that have been transferred to the whole body, intratumoral injection can't be done What should we do at this time? Therefore, the research and development of intravenous oncolytic virus must be necessary In fact, there are more and more researches on intratumoral injection in the industry at present How to solve the problem of neutralizing antibody and the safety brought by systemic injection in the next step will be an important development direction < br / > in my opinion, intratumoral injection and intravenous injection are complementary and cannot replace each other < br / > breakthrough: combination of production, learning and research < br / > Q < br / > you mentioned that you hope to speed up the research and development process of oncolytic virus in the future Can you elaborate on the combination of production, learning and research? < br / > week < br / > the R & D of oncolytic virus itself has a high threshold, which needs a lot of basic scientific research as support Each oncolytic virus has its own particularity of biological mechanism < br / > in the development of oncolytic virus, the most important thing is how to modify the virus It may take decades of accumulation to design how to reconstruct the virus gene Broadly speaking, the combination of oncolytic virus and immunotherapy drugs will also involve a series of specific problems, which can only be realized on the basis of your sufficient understanding of Virology < br / > so, I can only say that I am a scholar studying herpes virus, not a virologist in general, because the characteristics and mechanism of each virus are very different For an enterprise or team, it is not advisable to expand the product line from one virus to another What if the market really needs different oncolytic virus products? This is the necessity of the combination of production, learning and research < br / > on the other hand, a oncolytic virus is not effective for all tumors, and the effect is generally less than 30% Secondly, take breast cancer for example, it has different genotypes, and different genotypes have different sensitivity to oncolytic virus, so the overall efficacy is very different < br / > so what to do with those 70% insensitive tumors? This is a very duplicated subject, and we should go back to basic scientific research From this point of view, the research on "production, learning and research" is particularly important Without early accumulation, it is impossible to get new products < br / > Q < br / > at present, the preparation technology of oncolytic virus is basically mature, but it has not seen large-scale industrial application Is it also related to the combination and accumulation of production, learning and research? < br / > week < br / > for a start-up oncolytic virus company, the long-term research accumulation process from 0 to 1 really restricts the iteration and development of its product line But for those companies that get the patent products of oncolytic virus, the industrialization of oncolytic virus is not so easy < br / > the production of oncolytic virus is different from small molecule and antibody Over the years, the latter has established a relatively perfect production process to facilitate industrialization and expansion of production But the characteristics of each oncolytic virus are different, and the bottlenecks encountered in the production process are also different Generally speaking, the larger the virus is, the harder it is to produce, and the output will not go up; the smaller the virus is, the output can be guaranteed, but the stability of the virus is a challenge It is not only in China, but also abroad It is very difficult to improve the production of virus The virus is not a synthetic process in vitro, but needs to be replicated in living cells and then purified So, after getting a recombinant oncolytic virus, how to promote small-scale trials, process validation, process amplification, and finally to mass production, clinical and marketing, this path is very difficult to take < br / > the "card position" of Rozman Research Institute < br / > Q < br / >: in 2015, you led the establishment of Shenzhen Rozman international transformation Medical Research Institute, focusing on the introduction of scientific research projects integrating innovation and industrialization What is the starting point? < br / > week < br / > biomedicine is a short board in Shenzhen On the one hand, although Shenzhen is very supportive of biomedical entrepreneurship, the development idea is not the same as it industry, which can be directly applied to biomedical industry; on the other hand, due to the need for third-party cro companies such as production and pre clinical research, none of the major domestic cro companies are in Shenzhen, which means the start-ups in Shenzhen, The human cost, time cost and expense cost are all great challenges In turn, there are not enough cro companies in Shenzhen, and the arrival of biomedical start-ups in Shenzhen has become another obstacle In fact, this is a