Oncolytic virotherapy is a cancer treatment that uses genetically engineered viruses to target and destroy cancer cells. These viruses selectively infect and multiply within tumor cells, leaving healthy tissues unharmed. This therapy acts as a form of immunotherapy, directly eliminating cancer cells while also activating the patient’s immune system to fight the disease throughout the body. The concept of using viruses to combat cancer dates back to observations in the early 1900s, when tumor regression was noted in patients with natural viral infections.
The Dual Mechanism of Action
Oncolytic viruses work through a dual mechanism: direct oncolysis and immune system stimulation. The engineered virus first selectively infects cancer cells, exploiting features like defects in antiviral responses or overexpression of viral receptors unique to these cells. Once inside, the virus replicates extensively, producing numerous new viral particles within the cancer cell.
This replication process leads to the bursting of the cancer cell (lysis), which releases newly formed virus particles to infect neighboring tumor cells. This direct killing of cancer cells is a primary way the therapy reduces tumor size.
The bursting cells also release tumor-associated antigens and other danger signals, effectively “unmasking” the cancer to the immune system. These signals attract immune cells and trigger a robust anti-tumor immune response. This stimulation can transform an immunosuppressive tumor environment into an inflammatory one, making the cancer more visible and vulnerable to the body’s defenses. The activated immune system can then target not only the directly infected cells but also distant cancer cells, offering a broader, systemic anti-cancer effect.
Types of Viruses Used
Scientists genetically modify specific viruses for oncolytic virotherapy, ensuring they selectively target cancer cells while remaining safe for healthy tissue. This engineering often involves deleting virulence genes that cause disease in normal cells, or inserting genes that enhance replication specifically in tumor cells. Some modifications also add genes that produce immune-stimulating proteins, further boosting the body’s anti-cancer response.
One prominent example is the Herpes Simplex Virus (HSV), particularly HSV-1, modified for oncolytic therapy. Its genome can be engineered to restrict replication to tumor cells and express therapeutic genes. Adenoviruses are another frequently explored type, often used in clinical trials due to their established safety profile from gene therapy research. Vaccinia virus, a large virus historically used in vaccines, also serves as an oncolytic agent. Its size allows it to carry multiple therapeutic genes, making it versatile for engineering.
Approved Treatments and Targeted Cancers
The first oncolytic virus approved by the U.S. Food and Drug Administration (FDA) is Talimogene laherparepvec, known as Imlygic (T-VEC). Approved in October 2015, this therapy treats certain advanced melanomas. T-VEC is indicated for unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma that has recurred after initial surgery.
Imlygic is a modified herpes simplex virus type 1 that replicates within tumors and produces GM-CSF, an immune-stimulating protein. Its approval was based on clinical trials showing significant increases in durable response rates. While T-VEC’s primary approved use is for melanoma, its success has spurred extensive research into oncolytic viruses for treating various other cancers.
Treatment Administration and Potential Side Effects
Oncolytic virotherapy is commonly administered via intratumoral injection, directly into the tumor. This targeted approach concentrates the virus at the tumor site, limiting exposure to healthy parts of the body. For visible tumors, injections are direct; for deeper lesions, ultrasound guidance may be used.
Following the initial dose, subsequent injections are given at regular intervals, such as every two weeks, for several months. As with any cancer treatment, oncolytic virotherapy can cause side effects, though they are generally more manageable than those of traditional chemotherapy.
The most frequently reported side effects are flu-like symptoms, including fever, chills, fatigue, and muscle aches. Patients may also experience pain or a rash at the injection site. These symptoms are mild to moderate and resolve within a few days. Less common but more severe side effects can include cellulitis, a bacterial skin infection, or other reactions related to immune activation.
The Future of Virotherapy Research
Research in oncolytic virotherapy is advancing, with a focus on combination therapies to enhance effectiveness. Scientists are exploring oncolytic viruses in conjunction with other immunotherapies, particularly immune checkpoint inhibitors like pembrolizumab (Keytruda) or nivolumab (Opdivo).
The oncolytic virus can “prime” the tumor by causing cell lysis and releasing tumor antigens, making the tumor more visible and responsive to the immune system. This priming effect can transform immunologically “cold” tumors, which do not respond well to checkpoint inhibitors, into “hot” tumors with increased immune cell infiltration. The checkpoint inhibitors then help unleash the immune system’s full anti-tumor potential by blocking inhibitory signals. This synergistic approach has shown promising results in clinical trials across various cancer types.
Clinical trials are investigating oncolytic viruses for various cancers beyond melanoma, including brain cancers like glioblastoma, bladder cancer, and liver cancer. This ongoing research aims to refine existing therapies, develop new viral agents, and optimize combination strategies to provide more effective and durable treatments for a wider range of patients.