The latest data of the two drugs are announced! Oncolytic virus has become a heavy weapon to treat the "king of brain cancer"?

Founded in 2015, Oncorus is a clinical-stage oncolytic virus therapy development company with a pipeline involving two areas: modified HSV and synthetic viruses, in addition to ONCR-719, there is also a drug candidate ONCR-177 for the treatment of melanoma, head and neck squamous cell carcinoma and triple-negative breast cancer, which is currently undergoing Phase 1 clinical trials
.

▲ Oncorus pipeline Source: The company's official website

There are also two investigational therapies in the synthetic viral pipeline, both using LNP to deliver the RNA viral genome (vRNA), namely coxsackievirus A21 (CVA21), ONCR-021 for the treatment of non-small cell lung cancer, hepatocellular carcinoma, clear cell renal cell carcinoma, melanoma, and optimized Seneca Valley virus (SVV), ONCR-788 for the treatment of small cell lung cancer, prostate cancer, and other neuroendocrine
。

Candel Therapeutics：CAN-3110

CAN-3110 is a replicating HSV oncolytic virus, in which the expression of the gene ICP34.
5 responsible for viral replication is controlled by a nestin promoter, enabling the virus to selectively replicate in tumor cells, and the replication ability is significantly higher
than that of the commonly used ICP-34.
5 deletion virus.
Lhomin is highly expressed in glioma cells and other tumor tissues, but is absent
in healthy adult brains.
The effects
of multiple doses of CAN-3110 on recurrent glioblastoma are currently being evaluated in Phase 1 clinical trials.

The data were obtained from 41 patients who received CAN-3110, of whom 40 received a single injection and one patient received two injections
.

• No dose-limiting toxicity was observed;

• The median overall survival was 11.
  6 months;

• The diversity of the T cell receptor pool after CAN-3110 administration has been reported to correlate with overall survival, and in-depth biomarker analysis has shown that activated CD4+ and CD8+ T cells and effector cells have statistically significant expansion in multiple tumor lesions after a single injection of CAN-3110
  .
  

Next, the company will investigate whether multiple injections of CAN-3110 over time can further improve overall survival
.

Founded in 1999, Candel Therapeutics is a clinical-stage biopharmaceutical company focused on treating cancer
through viral immunotherapy.
Candel's engineered virus aims to induce tumor cell death through direct virus-mediated cytotoxicity, releasing tumor neoantigens while creating a microenvironment
conducive to inflammation at the injection site.
On October 26, 2022, Candel announced a collaboration with the University of Pennsylvania to join forces with Carl June, the "father of CAR-T", to use oncolytic viruses to help CAR-T therapy conquer solid tumors
.

▲ Candel pipeline Source: The company's official website

Candel's enLIGHTEN™ discovery platform is the first HSV-based system iterative discovery platform that leverages human biology and advanced analytics to create new viral immunotherapies
for solid tumors.
At present, Candel has established two viral immunotherapy platforms, based on novel genetically modified adenovirus and HSV constructs, CAN-2409 is the main candidate for adenovirus platform, clinical trials for prostate cancer have progressed to phase 3 clinical trials, and CAN-3110 is the main candidate for HSV platform
.

Oncolytic viruses and gliomas

Glioma accounts for about 46% of intracranial tumors, is a refractory intracranial primary malignant tumor, its incidence and mortality rate are in the forefront of malignant tumors, among which glioblastoma, the highest degree of malignancy, recurrence rate is as high as nearly 100%, and the overall median survival is about 15 months
.
During the progression of glioma, there are fewer new mutations and neoantigens, which are "cold tumors", containing a small number of immune cells and limited anti-cancer effects
.

Oncolytic virus selectively replicates in tumor cells, leading to tumor cell lysis, and at the same time can destroy the tumor microenvironment, making the tumor "from cold to hot", and the tumor antigens released after tumor cell lysis can be mediated by the immune system, induce anti-tumor immune response, and specifically kill malignant tumors, therefore, oncolytic viruses have become a heavy weapon
for the treatment of brain tumors.

As early as 1999, Csatary and Bakács reported in detail the treatment of a 14-year-old man with recurrent glioblastoma, who was injected intravenously with Newcastle disease virus (NDV) MTH-68/H multiple times within 2 years, and the tumor volume was significantly reduced
.

Among the many types of oncolytic viruses, HSV-1 has natural neurotropics, the first reported genetically modified HSV-1 is the oncolytic virus research of glioma, in June 2021, Daiichi Sankyo's oncolytic virus product Delytact (teserpaturev/G47∆) was conditionally approved by the Japanese Ministry of Health, Labor and Welfare (MHLW), which is a third-generation HSV-1 for the treatment of malignant gliomas.
It is also the world's first oncolytic virus product
approved for the treatment of malignant gliomas.

In addition, other types of oncolytic viruses can also be used to treat gliomas, such as the genetically modified human adenovirus type 5 (hAd5) Delta-24-RGD; The combination therapy of oncolytic virus carrying the therapeutic gene has also been verified in preclinical and clinical trials, and is effective against gliomas without showing obvious toxicity
.

brief summary

Glioma recurrence rates are high, while patients with recurrent gliomas have a poor prognosis, with a median survival of less than one year
.
Although a variety of emerging treatment methods for glioma have made continuous progress in recent years, its prognosis is still unsatisfactory, and the survival of patients has not been significantly improved, and there is an urgent need to seek new treatment strategies
clinically.
With the further understanding of this tumor and oncolytic virus, and the gradual development of gene editing technology, oncolytic virus is expected to become a sharp blade
for the treatment of glioma.

Resources:

1.
com/article/releases/ oncorus-presents-preclinical-data-supporting-oncr-719-an-armed-hsv-1-vector-engineered-to-use-the-epidermal-growth-factor-receptor-egfr-egfrviii-for-viral-entry-in-glioblastoma-at-the-2022-society-for-neuro-o ncology-annual-meeting

2.
com/article/releases/ candel-therapeutics-announces-oral-presentation-of-updated-data-from-its-phase-1-clinical-trial-of-can-3110-in-41-patients-with-recurrent-high-grade-glioma-at-the-society-for-neuro-oncology-27th-annual-meetin g

3.
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