Triple-negative breast cancer (TNBC) accounts for about 15% of all breast cancer cases. Compared with other types of breast cancer, triple-negative breast cancer is more likely to spread metastasis and recurrence, and lacks therapeutic targets. Therefore, the prognosis of patients is poor, which has been a difficulty in the treatment of breast cancer.
Triple-negative breast cancer patients are lack of three therapeutic targets: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2), and thus lack therapeutic agents. Currently, the standard therapy for early triple-negative breast cancer is chemotherapy, as well as pembrolizumab, but these therapies have significant side effects. Many studies have shown that patients with higher levels of immune cells tend to respond better to treatment. This suggests that drugs that stimulate the immune system may be beneficial in patients with triple-negative breast cancer.
Oncolytic virus (Oncolytic viruses) is a promising therapeutic approach for solid tumors. After direct injection into the tumor, oncolytic virus targets cancer cells without affecting normal cells and replication in cancer cells; and can further trigger a systemic immune response to kill cancer cells.
On February 9,2023, researchers at Mofitt Cancer Center published a clinical research paper entitled: Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial in Nature Medicine, a leading international medical journal.
In this phase 2 clinical trial, 37 patients with triple-negative breast cancer received standard chemotherapy for T-VEC before surgery. Residual tumor burden (RCB) was used to assess treatment, 45.9% of patients (17 / 37) achieved complete response after treatment, and 89% (33 / 37) had no disease within two years of treatment.
talimogene laherparepvec (T-VEC) is a modified oncolytic virus therapy for herpes simplex virus type 1 (HSV-1) developed by Amgen, which was approved by the FDA for advanced melanoma in 2015 and is the first oncolytic virus therapy approved by the FDA.
T-VEC contains the coding sequence of GM-CSF protein that stimulates the immune system, and after injection into the tumor, it can cause the lysis of tumor cells and release tumor-derived antigen and GM-CSF protein, accelerating the antitumor immune response.
In this clinical trial, the study team evaluated the effect of giving a combination of T-VEC oncolytic virus and standard chemotherapy before surgery in a triple-negative breast cancer patient. In this phase 2 clinical trial of 37 patients with triple-negative breast cancer, 45.9% achieved disease remission and 89% had no relapse within two years of treatment. The safety of the combination was not significantly different except for presenting with higher levels of low fever, chills, headache, and injection site pain than standard chemotherapy.
The team also analyzed immune biomarker levels and assessed whether these biomarkers correlated with patient response. They found that most tumor samples had higher levels of activation of antitumor T cells and immune signaling pathways during the first 6 weeks of treatment. Patients who responded better to treatment had higher CD8 T cell levels at week 6 than those who did not respond to treatment. These observations suggest that early activation of the immune response may lead to better outcomes in triple-negative breast cancer patients.
Professor Hatem Soliman, the leader in the clinical trial, said the results showed that T-VEC oncolytic virotherapy combined with standard chemotherapy can increase responses in patients with high-risk, early triple-negative breast cancer. There is evidence of robust immune activation within the tumor, and T-VEC combined with current chemoimmunotherapy for triple-negative breast cancer is warranted.
