Fighting fire with fire
Writing | Yan Xiaoliu
Source | “Medical Community” Public Account
Viruses can cause cancer and can also act as “cancer killers.”
At the 2022 European Society of Medical Oncology Annual Meeting (ESMO) held recently, British scientists submitted research saying that genetic modification of the herpes simplex virus can infect and destroy cancer cells, while activating Human immune system to treat cancer.
A phase I clinical trial involving 39 patients with advanced cancer showed that 1/4 of the subjects had a significant effect, and the tumor stopped growing or shrank. One of the patients with salivary gland cancer had complete tumor disappearance and no recurrence at 15-month follow-up.
Image caption: A recent photo of Krzysztof Wojkowski, an enrolled patient with salivary gland cancer. /The Telegraph
Using viruses to kill cancer cells
Comprehensive media reports, 39-year-old construction worker Krzysztof Wojkowski (Krzysztof Wojkowski) is the “lucky one” mentioned above.
In May 2017, Krzysztof was diagnosed with salivary gland cancer. This is a tumor that begins with abnormal cell growth in the salivary glands and occurs more frequently in oral and maxillofacial tumors.
After comprehensive treatment including surgery, his condition was not controlled and the tumor continued to grow.
In 2020, Krzysztof joined the trial group at the Cancer Institute, The Royal Marsden NHS Foundation Trust. Enrollees suffered from a variety of cancers, including skin cancer, esophageal cancer, and head and neck cancer. The same is that they are both terminally ill with cancer and receiving hospice care.
“This is my last hope,” Krzysztov told The Telegraph.
After enrollment, Krzysztof received a virus injection every two weeks for a total of 8 injections. The starting dose is 10ml, in which the virus content reaches 1×106PFU/ml. The total dose of 7 injections thereafter was unchanged, and the virus content was 1 x 107 PFU/ml.
The injected virus, named RP2, is a gene-edited, oncolytic type I herpes simplex virus with enhanced potency.
Gene editing involves insertion of granulocyte-macrophage colony-stimulating factor (GM-CSF), cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody, and codon-optimized Gibbon leukemia virus (GALV) glycoprotein (GP) gene with its R transmembrane peptide removed (GALV-GP-R-).
These modifications will attack cancer in two dimensions: First, the virus will infect both cancer cells and normal cells, making it harmless because it cannot replicate in normal cells. But inside cancer cells, the virus can replicate in abundance until the cancer cell ruptures and is destroyed. Second, the release of GM-CSF rapidly activates the body’s immune system to find and kill cancer cells.
After treatment, Krzysztof improved significantly. A comprehensive examination showed that the cancer cells in his body were completely eradicated.
“I’ve been cancer free for 2 years since I was enrolled. I’m back at work, spending quality time with my family, and doing anything.”
Picture description: Illustration of the mechanism of action of RP2. /ESMO
Safety studies pay off
At the ESMO Annual Meeting in September, the aforementioned study leader, Professor Kevin.J.Harrington, Cancer Institute, Royal Marsden NHS Foundation Trust ) to give an oral presentation.
According to him, the study has now completed Phase 1 Part 2a and the results are encouraging.
First, biopsies before and after RP2 injection showed positive changes in the tumor immune microenvironment. More immune cells, including CD8+ T cells, could be detected in the injected area.
Second, 3 of 9 patients who received a single-agent injection of RP2 were observed to respond with significant tumor shrinkage. Except for Krzysztof, one patient with esophageal cancer with liver metastases maintained the curative effect for more than 18 months, and the other patient developed disease progression after 15 months of response.
Picture description: Illustration of the efficacy of RP2 single-drug injection. /ESMO
Third, 30 subjects were treated with nivolumab on the basis of virus injection. This is a monoclonal antibody drug targeting PD-1, which can modulate the immune system, prompting T cells to play an immune surveillance role to eliminate cancer cells.
The results showed that the combination therapy was well tolerated and had durable systemic responses. In cutaneous melanoma, uveal malignant melanoma (malignant intraocular tumor), and head and neck squamous cell carcinoma, the objective response rates were 44.4%, 25%, and 33%, respectively.
All responding patients (seven) had previously experienced immunotherapy failure. After this combined treatment, 6 patients had sustained responses >425 days.
Picture description: Illustration of the efficacy of RP2 single-drug injection. /ESMO
Further analysis showed that with either single-agent or combination therapy, side effects mainly included mild fever and fatigue, and no medical intervention was required.
Kevin Harrington said: “Phase I clinical trials are early-stage safety trials, the main purpose of which is to test the safety of the treatment. It is rare to see such a high treatment response rate. “
Gene-edited oncolytic herpes simplex virus could be a new treatment option for some patients with advanced cancer, including those who do not respond to immunotherapy, he added. In the future, the study will include more patients with solid tumors, including breast cancer and non-small cell lung cancer. “I wonder if I can continue to see significant benefits as the number of patients increases.”
It’s not the first time a virus has treated cancer
This isn’t the first time scientists have used a virus to fight cancer, the BBC reported.
In October 2015, T-VEC, an oncolytic virus product based on herpes simplex virus type I as a carrier, was approved for marketing in the United States for the local treatment of first recurrent and unresectable melanoma. Clinical studies involving 64 authoritative research centers around the world have shown that about 16.3% of patients given T-VEC showed durable treatment responses over a period of more than 6 months. In contrast, only 2.1% of the control group showed durable responses.
In September 2017, “Cell” magazine published an article stating that T-VEC combined with PD-1 antibody drug therapy had a remission rate of 62% for melanoma, of which 33% were complete remission. This is much higher than the expected response rate for PD-1 antibody drugs alone.
In 2020, the monthly journal of the British Society for Immunotherapy of Cancer published a review, analyzing 97 public clinical trials related to oncolytic viruses from 2000 to 2020.
The article shows that oncolytic virus drugs under development have a variety of vectors, including adenovirus, herpes virus, vaccinia virus and reovirus. As a novel method, oncolytic virus can treat malignant tumors of different types and stages of progression, and has achieved phased results in clinical studies of various cancer treatments.
Kevin Harrington told the BBC that RP2 could be seen as an enhanced or upgraded version of T-Vec that could kill cancer cells more efficiently once it entered.
References:
[1]An open-label,multicenter,phase I study of RP2 as a single agent and in combination with nivolumab in patients with solid tumors:Safety,efficacy,and biomarker results.Annals of Oncology.(2022)33(suppl_7):S356-S409.10.1016/annonc/annonc1059
[2]Cancer-killing virus shows promise in patients.BBC
[3]‘Miracle’herpes treatment eradicates tumours in terminally-ill cancer patients.The Telegraph
Source: Medicine
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Editor in charge: Wan Shunshun
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