New Therapy Shows Promise for Treating Basal Cell Carcinoma with TVEC

Promising New Therapy for Basal Cell Carcinoma Shows Encouraging Results

Basal cell carcinoma (BCC) is the most common form of skin cancer, often appearing in areas of the skin that have been chronically exposed to sunlight, such as the face, ears, neck, and scalp. While the majority of BCCs can be effectively treated with surgical excision, certain cases—especially locally advanced tumors—can present significant challenges. These tumors may be large, deeply invasive, or located in areas where surgical removal can cause functional impairment or disfigurement.

In an exciting development, a research team from MedUni Vienna and University Hospital Vienna has explored a new therapeutic approach that shows considerable promise for patients with difficult-to-treat basal cell carcinomas. This approach involves the use of Talimogene Laherparepvec (TVEC), a genetically modified herpes simplex virus, which has been shown to reduce tumor size in patients, potentially making surgery more straightforward and even leading to complete tumor regression in some cases. This groundbreaking research was published in Nature Cancer, one of the most prestigious journals in the field of oncology.

Understanding Basal Cell Carcinoma and Treatment Challenges

Basal cell carcinoma arises from the basal cells, which are located at the bottom of the epidermis. These cancers typically develop in areas of the skin that are frequently exposed to ultraviolet (UV) radiation, such as the face, neck, and ears. Although BCC is rarely metastatic and is considered highly treatable, when the tumor becomes advanced or located in a delicate area, treatment options become limited.

Locally advanced BCCs—those that have grown deeply into the surrounding tissue—pose particular challenges. Surgical excision may require extensive tissue removal, often necessitating skin grafts or flaps, leading to functional or cosmetic deficits. In such cases, a non-surgical approach to shrink the tumor prior to surgery could significantly improve both the outcome of the surgery and the patient’s quality of life.

The Role of TVEC in Basal Cell Carcinoma Treatment

Talimogene Laherparepvec (TVEC) is a modified form of the herpes simplex virus (HSV), a common virus that causes cold sores. Scientists have engineered the virus to selectively infect and destroy tumor cells while simultaneously stimulating the immune system to target and fight the cancer. TVEC is currently approved for use in treating superficial melanoma metastases, but this new study explores its application in treating basal cell carcinoma.

The study aimed to investigate whether TVEC could serve as a neoadjuvant therapy—that is, a treatment given before surgery—to reduce the size of basal cell carcinomas in patients for whom traditional surgery would be more invasive or complicated. The goal was to shrink the tumor to a manageable size, thus allowing for simpler, less disfiguring surgery without functional compromise.

Study Design and Key Findings

The study involved 18 patients with large basal cell carcinomas, primarily located in areas where the tumors could require flap surgeries or skin grafts. These patients were administered six intralesional injections of TVEC over a 13-week period. After the therapy, the tumors were surgically removed, and the researchers analyzed the results.

Key findings from the study include:

• Tumor Shrinkage: In half of the patients, the tumor size was reduced by approximately 50%, making it possible to close the wound directly after surgery, rather than requiring a graft or flap.
• Complete Regression in Some Cases: A third of the patients showed complete tumor regression, with no living tumor cells found in the post-surgical histological examination. This was a particularly striking result, suggesting that TVEC might not only shrink tumors but potentially eradicate them altogether.
• No Disease Progression: In all cases, the tumors shrank or remained stable, with no signs of tumor growth under the treatment.
• Well-Tolerated Treatment: TVEC was generally well-tolerated by the patients, with no serious adverse effects reported.

As summarized by the lead investigator, Christoph Höller, who is the head of the Skin Tumor Centre at the Department of Dermatology, "The use of TVEC reduced the size of the tumors in half of the patients to such an extent that surgery with direct wound closure was possible. In a third of the cases, subsequent histological examination showed no more living tumor cells." He added, “The treatment was well tolerated by the patients and simplified the surgical process.”

Study Reference: https://www.nature.com/articles/s43018-024-00879-x

Mechanism of Action: How TVEC Works

TVEC works through a two-pronged approach: direct oncolysis and immune system activation.

1. Oncolysis: TVEC is genetically modified to selectively infect and replicate inside tumor cells. As the virus replicates, it causes the tumor cells to burst, releasing viral particles and destroying the cancerous cells. Importantly, TVEC specifically targets tumor cells, sparing normal, healthy cells.
2. Immune System Activation: As the tumor cells break down, the immune system is stimulated to recognize the tumor antigens, effectively "training" the body’s immune system to attack the cancer. This immune response continues even after the virus has been cleared, providing long-term protection against cancer recurrence.

These combined effects make TVEC a unique and potentially game-changing therapy, especially for locally advanced tumors that would otherwise be difficult to treat surgically.

A Potential Solution for High-Risk Patients

TVEC presents a promising option for patients with basal cell carcinoma who may not be ideal candidates for traditional surgery. Locally advanced tumors that require extensive surgical resection or result in significant cosmetic or functional impairments could benefit from this therapy. TVEC could offer these patients a less invasive option, reducing the need for complex skin grafts or flap surgeries, and improving the aesthetic and functional outcomes.

Additionally, the immune-stimulating properties of TVEC may lead to better long-term outcomes by reducing the risk of recurrence. The researchers also pointed out that, in some patients, the treatment could potentially avoid the need for surgery altogether if the tumor is fully eradicated.

Next Steps: Further Research and Larger Trials

Although these initial results are promising, further research is necessary to confirm the efficacy of TVEC in a larger patient population. The current study included a relatively small sample size, and additional trials are required to assess the long-term benefits and risks of TVEC in treating basal cell carcinoma.

Future studies should explore:

• The optimal dosing schedule and method of TVEC administration.
• The combination of TVEC with other therapies to improve outcomes.
• The effectiveness of TVEC in different stages of basal cell carcinoma.

It is also important to investigate whether TVEC can be used in other forms of skin cancer or other solid tumors. Given the success in melanoma and now basal cell carcinoma, there is potential for broader applications in oncology.

Conclusion: A New Hope for Treating Basal Cell Carcinoma

The results of this study offer new hope for patients suffering from advanced basal cell carcinoma, particularly those whose tumors are located in delicate areas or are large enough to require complex surgical procedures. TVEC therapy not only shrinks tumors but may also improve the effectiveness and cosmetic outcomes of surgery. In some cases, it may even eliminate the tumor altogether.

For now, TVEC represents a promising neoadjuvant therapy that could change the landscape of basal cell carcinoma treatment. With further research and larger clinical trials, this innovative treatment may become a standard option for patients facing difficult-to-treat BCCs, improving both survival outcomes and quality of life.