Glioblastoma is a common cancer in the central nervous system. Under normal circumstances, a variety of treatment methods including traditional treatments such as chemotherapy, surgery, and radiotherapy cannot effectively prolong the survival of patients.
There are many reasons for this. Because the tumor is very invasive, and the function of the brain where the tumor is located is very important to the human body, local therapy is greatly limited. Moreover, due to the existence of the blood-brain barrier, and the difficulty of inducing apoptosis in such tumor cells, and the lack of reliable target drug targets, there are many obstacles to systemic treatment.
As for immunotherapy, due to the special immune environment of the central nervous system, there are many differences in the development strategy of drugs for the treatment of glioblastoma compared to the treatment of other tumors. The oncolytic virus seems to be a potential tumor immunotherapy.
Oncolytic viruses are not initially considered as immunotherapy because it has been previously thought that oncolytic viruses can only selectively replicate within tumors and selectively destroy tumor cells. But in fact, oncolytic viruses can also trigger anti-tumor immune responses.
Viruses commonly used in oncolytic viral therapy include retrovirus, adenovirus, HSV, poliovirus, and measles virus.
The 2015 ASCO meeting revealed a poliovirus-based treatment for glioblastoma. The ribosomal entry site of the virus PVSRIPO used in this therapy was replaced with the ribosome entry site of the human type 2 rhinovirus.
PVSRIPO can infect CD155-expressing cells and replicate in these cells. Since CD155 is highly expressed in glioblastoma, it is theoretically suitable for glioblastoma.
At the 2015 ASCO meeting, some phase I clinical data were published involving 24 patients. The 2-year overall survival rate was 24%, and the median overall survival was 12.5 months.
The updated data for 2016 shows that 3 patients (13%) survived 3 years after treatment. In 2016 PVSRIPO was awarded the FDA for breakthrough therapy certification.
At the 22nd International Conference on Brain Tumor Research and Treatment held in Norway this Tuesday, Duke University once again updated the Phase I clinical study data of PVSRIPO, and also published relevant data in the New England Journal.
From the data of this paper, we can see that compared with the previous data, the patient’s three-year survival rate has changed from the previous 13% to the current 21% (8 patients).
In this study, 61 patients with recurrent glioblastoma were treated with poliovirus therapy. The surgeon implants the catheter into the patient’s brain and delivers the PVSRIPO virus through the catheter into the tumor.
During the dose-escalation phase, severe toxicity was seen in patients in the high-dose group (billion TCID50), and the researchers therefore reduced the dose of the virus.
The median overall survival of all 61 diseases was 12.5 months. The clinical study did not establish a control group, but rather compared historical data from the Duke University’s medical history. The historical control group had 104 patients with the same recurrent glioblastoma. The median overall survival of this control group was 11.3 months.
The one-month difference in lifetime can only be considered to be unsatisfactory. But researchers also counted the proportion of patients who survived at a specific time.
After one year of treatment, 54% of patients survived, compared with 45% in the historical control group. After 18 months of treatment, the treatment group was the same as the historical control group, and 23% of the patients survived.
However, after 18 months, Duke University researchers found that patients in the treatment group began to exhibit survival advantages.
After two years of treatment, 21% of patients in the treatment group survived, compared with only 14% in the historical control group. After three years of treatment, the difference in survival between the treatment group and the historical control group further widened, and 21% of the patients in the treatment group survived, compared with 4% in the historical control group.
There is a big difference between immunotherapy and traditional therapy. Although the response rate may not be very high, once some immunotherapy is effective, the patient’s response time is usually very long. We also saw similar phenomena in this clinical trial.
However, it should be noted that the analysis data for 2016 showed that the survival rate of patients after 3 years of treatment was 13% (3 persons), while the current data was 21% (8 persons). Due to the small scale of clinical trials, it is still difficult to judge how large the impact of the therapy will be.
Istari Oncology has patented PVSRIPO from Duke University. Dani Bolognesi, Istari’s CEO, said that in phase I clinical trials, they found that a patient who used both chemotherapy and immunotherapy responded well to combination therapy. Therefore, they plan to compare the effectiveness of PVSRIPO versus PVSRIPO alone in phase II clinical trials.