T-VEC oncolytic virus for breast cancer nearly 90% no recurrence within two years

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T-VEC oncolytic virus for breast cancer nearly 90% no recurrence within two years

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T-VEC oncolytic virus for breast cancer nearly 90% no recurrence within two years!

The latest research ushers in a new situation in the treatment of refractory cancer?

Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance the response of triple-negative breast cancer to neoadjuvant chemotherapy.

On February 9, a new anti-cancer therapy involving oncolytic virus “Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial” was published in the journal “Nature Medicine”, sharing the Results of a phase 2 clinical trial of oncovirus T-VEC combined with standard chemotherapy in patients with early triple-negative breast cancer .

Studies have shown that more patients with triple-negative breast cancer who received a combination of oncolytic virus and chemotherapy before surgery disappeared cancer cells in surgically removed tissues, and nearly 90% of patients had no disease recurrence two years after surgery .

https://www.nature.com/articles/s41591-023-02210-0

Research Background

Patients with triple-negative breast cancer lack expression of estrogen and progesterone receptors and have little expression of the HER2 protein.

Therefore, hormone therapy and drugs that target the HER2 protein receptor are not effective against this type of cancer.

The standard of care for early triple-negative breast cancer is cytotoxic chemotherapy, with the recent addition of pembrolizumab.

However, this approach has significant side effects.

Numerous studies have shown that patients with higher levels of immune cells within their tumors tend to respond better to treatment.

These observations suggest that drugs that stimulate the immune system may be beneficial in triple-negative breast cancer .

Oncolytic virus T-VEC

T-VEC is a modified herpes simplex 1 virus that includes the coding sequence for the protein GM-CSF, which stimulates the immune system.

It is injected directly into tumors and undergoes massive replication within tumor cells, causing tumor cells to break down and produce tumor-derived antigens.

Immune cells can recognize antigens, infiltrate tumors and target cancer cells for destruction .

This anti-tumor approach has little effect on healthy cells, which have normal anti-viral defense mechanisms and can therefore fight viruses by initiating an interferon (IFN) response.

Cancer cells often lack this mechanism, so the virus is able to multiply in them without limit.

Scientists have also deliberately modified the herpes simplex virus (HSV) type 1 that makes up T-VEC to make it more sensitive to the effects of interferon, thereby reducing the impact on healthy cells.

In addition, GM-CSF produced by the virus acts as a beacon to help recruit immune cells to the tumor.

The protein, GM-CSF, is released into the tumor microenvironment as cancer cells eventually rupture, where it stimulates nearby immune cells to gather and activate to attack cancer cells .

As cancer cells rupture, various tumor proteins are released, and the immune system can recognize and remember many tumor-associated antigens, which may prevent future cancer recurrence.

Research evaluation

T-VEC is approved for the treatment of advanced melanoma.

The researchers wanted to assess whether oncolytic viruses could also be used in combination with standard chemotherapy when given to patients with triple-negative breast cancer before surgery.

In a phase 2 trial involving 37 patients, 45.9% of patients achieved remission, 89% remained disease-free two years after treatment, and patients who achieved strong remission did not relapse .

Other than higher levels of low-grade fever, chills, headache, and pain at the injection site, the treatment did not differ significantly from previous expectations.

Separately, the researchers analyzed levels of immune biomarkers and assessed whether these correlated with patient response.

They found that most tumor samples had higher levels of antitumor T cells and activation of immune signaling pathways during the first six weeks of treatment. Patients who responded better to treatment had higher levels of CD8 T cells at week six than those who responded poorly to treatment.

These observations suggest that earlier activation of the immune response may lead to better outcomes in triple-negative breast cancer patients .

“Our findings suggest that T-VEC, when added to systemic chemotherapy, may increase response in high-risk early-stage triple-negative breast cancer,” Soliman said. ” There is evidence of robust immune activation within the tumor, necessitating the need for T-VEC combined with current chemoimmunotherapy should be further studied in triple negative breast cancer .”

References:

https://www.nature.com/articles/s41591-023-02210-0

T-VEC oncolytic virus for breast cancer nearly 90% no recurrence within two years

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