ESMO 2022: GMO herpes virus provides a deep secondary blow to advanced cancer

Researchers have long worked to work by directly destroying tumors and altering the tumor microenvironment (TME) to release tumor-derived antigens

Image: Carcinoma of salivary gland.

1.

Herpes viruses are a group of enveloped DNA viruses with similar biological characteristics and classified as Herpesviridae

HSV can be grown in a variety of cells, commonly used cell lines are BHK cells, Vero cells, Hep-2 cells and the like

Although the oncolytic virus uses the commonly used herpes simplex virus (HSV-1), it removes the part of the virus that is itself a threat to humans, and then modifies the virus so that the virus specifically looks for tumor cells and then invades and replicates to achieve the purpose of

This virus, called RP2, is a transgenic herpes simplex virus that, specifically, injects RP2 directly into the tumor, which multiplies in large numbers within the cancer cells and then ruptures the cancer cells from the inside; It also blocks a protein called CTLA-4, which acts as a "brake" on the immune system; Moreover, RP2 has been engineered to produce special molecules

Second, test the safety and dose of RP2

A team from the London Cancer Institute and the Royal Marsden NHS Foundation Trust evaluated nine patients' own anti-cancer viruses in an ongoing phase I trial, in combination with immunotherapy nivolumab in the initial 30 patients

The early study, sponsored by drug manufacturer Replimune, is testing the safety and dosage of RP2 and evaluating its ability to

After determining RP2D (¹⁰⁶ PFU/mL intratumorous (IT) once, followed by up to 7 additional doses of¹⁰⁷ PFU/mL via IT), a group of 30 patients (pts) were recruited and received RP2 plus nivo (240 mg Q2W for 4 months starting with the second RP2 dose followed by 480 mg Q4W for 20 months).

The genetically engineered RP2 virus injected directly into the tumor is designed to have a dual effect

RP2 has also been modified to produce molecules called GM-CSF and GALV-GP-R, which give the virus additional power to stimulate the immune system to fight cancer

3.

Patients who participated in the trial suffered from a variety of cancers: skin, esophageal and head and neck cancers

Three of the 9 patients treated with RP2 alone benefited from the treatment and saw their tumors shrink

Two other patients in the group, who had esophageal cancer and uveal melanoma — a rare type of eye cancer — had spread to the liver

7 out of 30 patients receiving RP2 and immunotherapy nivolumab also benefited
from treatment.

In this group, cancer growth stopped or shrank
in four-in-nine of patients with melanoma skin cancer, two-eighths of patients with eye cancer uveal melanoma, and one-third of patients with head and neck cancer.

Of the 7 patients who received combination therapy, 6 patients remained unprogressive
at 14 months.

All patients who participated in the trial had very advanced cancers that did not respond to standard care regimens or did not qualify
.

Fourth, turn on the anti-cancer immune response

The researchers looked at patient biopsies before and after RP2 injections and found positive changes in
the tumor's "immune microenvironment" (i.
e.
, the region around the tumor).
The injection results in the appearance of more immune cells in the region, including CD8+ T cells, and "turns on" genes
associated with the "anti-cancer" immune response.

The researchers found that most of the side effects of RP2 were mild—some of the most common side effects were fever, chills, and fatigue
.
None of the side effects were serious enough to require medical intervention
.

Next, the researchers hope to continue exploring the potential
of RP2 in more patients.

RP2 provides "two birds with one stone" for tumors

Study leader Professor Kevin Harrington, Professor of Bio-Cancer Treatment at the London Cancer Institute and Consultant Oncologist at the Royal Marsden NHS Foundation Trust, said:

"Our study shows that a genetically engineered anti-cancer virus can strike tumors once or twice — destroying cancer cells directly from within, while also calling on the immune system to fight them
.
"

"Such good response rates are rarely seen in early clinical trials because their primary purpose is to test treatment safety, and they involve patients with very advanced cancers whose
current treatment has stopped working.
"

"The results of our preliminary trials suggest that genetically engineered forms of herpes virus may be a new treatment option for some patients with advanced cancer — including those who haven't responded to other forms of immunotherapy
.
" I'd love to see if we will continue to see benefits as we treat more and more patients
.
”

Sixth, new treatment options

Although the therapy is still in the early stages of trial, the researchers say the RP2-based therapy successfully killed cancer cells
in a quarter of the patients.
These patients had different cancers, including skin, esophageal and head and neck cancers, and all were in advanced stages of cancer and did not respond
to other existing therapies.

The results showed that the tumors of the 3 patients who received RP2 treatment alone shrank, among which the tumors of the patients with salivary adenocarcinoma completely disappeared, and the cancer
did not recur after 15 months.
The cancers of two other patients with esophageal cancer and uveal melanoma have
shrunk.
Of the 7 beneficiaries who received the combination therapy, 6 had no cancer that had worsened
for 14 months.
In addition, most of the side effects reported by patients are fever, chills and fatigue without the need for medical intervention
.

For some patients with advanced cancer — including those who don't respond to other forms of immunotherapy — the GM herpes virus could become a new treatment option
.

Resources:

http://digitalpaper.
stdaily.
com/http_www.
kjrb.
com/kjrb/html/2022-09/27/content_542227.
htm?div=-1

#presentation-abstract-31731978491385