Enhanced Killing of TNBC Cells by Oncolytic Viruses

A diagnosis of triple-negative breast cancer (TNBC) means that the three most common types of receptors contributing to most breast cancer growth, estrogen, progesterone, and the HER-2/neu gene, are absent in the cancer tumor. Since the tumor cells lack the necessary receptors, common treatments such as hormone therapy and drugs that target estrogen, progesterone, and HER-2 are ineffective.

TNBC, which accounts for 10% -20.8% of all breast cancer pathological types, has special biological behavior and clinical pathological characteristics, and is more common in premenopausal women and obese people.

TNBC has the following characteristics:

High invasiveness with a high possibility to transfer to lungs and brain;

Risks of a relapse, 1-3 years is the peak period of relapse;

Low survival rate;

High tendency of mutation leading to the development of resistance.

For the treatment of triple-negative breast cancer, traditional methods include chemotherapy, surgery and radiotherapy. Besides, recent research shows that oncolytic virus combined immunotherapy may serve as a novel treatment with improved safety and efficiency.

Surgery

Surgery is the best treatment for local TNBC. Early TNBC is commonly suggested to receive breast-conserving surgery combined with radiation therapy, while high-risk patients with positive or unknown margins are advocated to have radical mastectomy.

Radiotherapy

Radiotherapy can be used as an important method for locally controlling TNBC. It is generally implemented after surgery. Postoperative combined radiotherapy can minimize the risk of local recurrence of TNBC. It is often applied to early TNBC.

Chemotherapy

Common chemotherapy regimens are adjuvant chemotherapy and neoadjuvant chemotherapy.

Chemotherapy can be administered in the neoadjuvant setting. Women with inoperable breast cancer may undergo neoadjuvant chemotherapy in hopes that it shrinks the tumor so it can be surgically removed, sparing the patient from having to undergo a mastectomy. Adjuvant chemotherapy refers to medicines administered after surgery for the treatment of breast cancer, which is designed to prevent recurrence of the disease, particularly distant recurrence.

Oncolytic virus combined immunotherapy

In recent years, immunotherapy has taken a wave in the field of cancer and has become a new means of treating cancer with world-renowned results. On March 8, 2019, Food and Drug Administration (FDA) approved Atezolizumab, the world's first drug for immunotherapy of TNBC. Then it approved Atezolizumab and Nab-Paclitaxel to treat patients with PD-L1 positive and unresectable locally advanced TNBC.

However, the pace of immunotherapy does not stop there. Oncolytic viruses (OVs), tumor-killing viruses that have the ability to replicate, become the key to open the new door of TNBC immunotherapy. In recent years, it has received extensive attention in tumor research for its innovation and excellent curative effect.

Given that OVs can induce anti-tumor immunity, a scientific study hopes to prove that these viruses help to make TNBC patients more sensitive to immunotherapy. This study establishes a mouse model that mimics the treatment process of newly diagnosed TNBC patients. In the time window of diagnosis and surgical resection, OVs therapy is inserted as a neoadjuvant treatment plan. After the surgery, OVs are combined with immunotherapy to make TNBC patients sensitive to immune checkpoint, thus to prevent recurrence. The results of this study show that oncolytic virus combined with immune checkpoint inhibitor therapy brings new hope for the treatment of TNBC, and it might become an effective means of tumor treatment.

Recently, the treatment of both early and advanced TNBC has seen significant improvements in response rates and survival outcomes. However, more researches are still required to explore more about oncolytic viral immunotherapy.