Engineered Virus Improves Anti-Tumor Immune Response, Study Shows

Engineered Virus Improves Anti-Tumor Immune Response, Study Shows

An engineered oncolytic virus that is capable of redirecting a patient’s immune cells against tumor cells may be a promising approach for treating cancer, according to a study.

The adenovirus was engineered to avoid one of the pitfalls of oncolytic viruses, which are viruses that prefer to attack cancer cells over other cells. That pitfall is that the immune system sees the virus as an invader and attacks it. The use of the engineered virus has shown promise in mice carrying human lung and colorectal cancer cells.

The study, “Oncolytic adenoviral delivery of an EGFR-targeting T cell engager improves antitumor efficacy,” was published in Cancer Research.

“We work with oncolytic adenoviruses, which are viruses modified to attack cancer cells exclusively, without attacking normal tissue,” Carlos Fajardo, the lead author of the study, said in a press release.

Adenoviruses, which can cause colds, gasteroenteritis, and conjuctivitis — or pinkeye — can be genetically modified to infect cancer cells without affecting healthy cells.

The engineered virus works several ways. It kills cancer cells directly, it delivers therapeutic genes to cancer cells, and it promotes immune responses against tumor cells expressing a certain protein.

But a major pitfall of this approach is that the immune system sees the virus as an invader, so most T-cells go after the virus instead of cancer proteins. When the virus does manage to infect cancer cells, the T-cells fight only those cancer cells the virus has reached, leaving the remaining cancer cells unharmed.

“What we are trying to do is redirect the immune system to attack the cancer cells instead of the virus. In this way, we not only prevent the virus from being eliminated from the organism too soon, but complement its action by adding that of T lymphocytes,” said Fajardo of Bellvitge Biomedicine Research Institute’s (IDIBELL)’s Cancer Virotherapy Research Group.

To achieve redirection, Fajardo and his colleagues used newly developed BiTE (bispecific T-cell engager) antibodies. They designed the antibodies to direct T-cells toward certain cancer-cell proteins, activating the immune system against the cancer rather than the virus.

“We modified the virus so that when it infects the tumor cell, it secretes a specific BiTE against the EGFR protein, which is over-expressed in many types of cancer,” Fajardo said.

Studies in lab-culture cells showed that the antibodies can prompt T-cells to attack cancer cells. Later, in mouse studies, the researchers discovered that an oncolytic virus that was carrying information for the BiTE antibody could trigger an increase in T-cells in a tumor, heightening the immune response.

“With these results, we will try to attract the interest of the companies that develop BiTEs to establish collaboration agreements for the clinical development of viruses armed with BiTEs,” said Dr. Ramon Alemany, the study’s lead author. “We are also exploring the development of viruses that target T lymphocytes against tumor stroma fibroblasts to eliminate them.”

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