What Is Dendritic Cell Therapy for Lung Cancer? Does This Gene Therapy Offer a More Efficient Approach to Management of Lung Cancer?

What Is Dendritic Cell Therapy?

Lung cancer is one of the main causes of cancer-related deaths in the USA and a major public health concern. Traditional lung cancer treatment procedures include chemotherapy, surgery and radiotherapy. A lot of research evidence shows that uncontrolled growth which is characteristic of cancer cells usually results from lack of surveillance and regulation of the immune response system. Dendritic cell therapy for lung cancer is a type of gene therapy which is based on the concept of using the body’s immune system to efficiently identify and destroy cancerous cells. Dendritic cell therapy is used to carry out modifications and reprogramming of the body‘s immune system so that it can recognize and attack left-over cancerous cells which are responsible for the development of “daughter tumors” or cancer metastases.

Thus, dendritic cell therapy is actually a therapy which can be used as a complementary and supportive role in combination with traditional cancer therapy. In the USA, approximately 50 percent of lung cancer related deaths occur in females. Many nations report similar high incidences of cancer metastases and in the last ten years not much progress has been made in improving survival of lung cancer patients. Dendritic cell therapy when combined with chemotherapy is a type of targeted gene therapy. In clinical trials it has shown improved prognosis for patients as it has provided an efficient procedure for delivering cytotoxic drug molecules and immunostimulatory factors or cells straight into the tumor.

How Does Dendritic Cell Therapy Work?

The immune system of the body plays a vital part by carrying out surveillance against tumors. Whenever it observes any unusual or abnormal cells, dendritic cells (these are highly specialized white blood cells with the function of picking up foreign cells) cause the activation of antigen-presenting cells (APCs) as well as activating tumor-specific, cellular and humoral effectors. Dendritic cells are able to pick up cancer cells. Inside the dendritic cells, the cancer cells are killed and bits of the foreign material is exhibited on the cell surface of the dendritic cells. As a demonstration of foreign matter on the cell surface of the dendritic cells is recognized by other cellular effector cells that move around in the body and destroy tumor cells which show the same kind of matter as that seen on the cell surface of the dendritic cells. This is how dendritic cells assist in teaching the effector cells of the immune system to find and destroy residual tumor cells which may prompt metastases. Therefore, dendritic cell therapy for lung cancer is based on the concept of dendritic cells expressing tumor material of the patient‘s own cancerous cells being introduced and stimulating a strong immune response against the tumor cells.

The Concept of Dendritic Cell Therapy

Dr. Steven Dubinett from the University of California has demonstrated that tumor-specific responses are not found in many patients suffering from cancer. The reason for this is that tumor cells seem to be nonimmunogenic, that is they do not have co-stimulatory molecules. Another reason is that humor cells build up an environment which protects them from the destructive nature of the normal immune system. Tumor cells do this by producing antagonistic mediators, down regulating antigen presentation and also through induction of tolerance in tumor-specific T cells of the immune system (Dubinett, 2004). This led to the concept of attempting to break this deadlock and activation of the patient’s immune system through the use of dendritic cell therapy. In dendritic cell therapy for lung cancer, APCs are obtained from the patient and then appropriately activated in the lab by exposing them to tumor antigens from the patient’s own cancerous cells. These APCs are then introduced into the body using several systemic or local routes. The optimal target is to introduce APCs modified in such a fashion that they retain higher immunogenic potential in situ for long durations after being reinfused (Sharma et al, 2003).

Benefits of Dendritic Cell Therapy

The main advantage of this gene therapy is that it provides supportive measures to traditional lung cancer treatments. The main benefits include the uptake and processing of multiple tumor antigens, the induction of more sensitive T-cell responses, the capacity to provide personalized treatment for each patient and eliminating the need of immunosuppressants and other harmful interventions. The most important benefit is the ability of dendritic cell therapy for lung cancer to deliver the therapeutic cells right into the cancerous tumor and speed up treatment.

References:

1. Cunningham C. (2004). Clinical update of gene based vaccines in lung cancer. Program and abstracts of the American Society of Gene Therapy 7th Annual Meeting; June 2-6, 2004; Minneapolis, Minnesota.

2. Dubinett S. (2004). Dendritic cell-based genetic immunotherapy for lung cancer. Program and abstracts of the American Society of Gene Therapy 7th Annual Meeting; June 2-6, 2004; Minneapolis, Minnesota.

3. Sekulic A, Haluska P Jr., Miller AJ, et al., Melanoma Study Group of the Mayo Clinic Cancer Center . (2008). Malignant melanoma in the 21st century: the emerging molecular landscape. Mayo Clin Proc. 2008; 83(7):825-846.

4. Sharma S, Yang SC, Batra RK & Dubinett SM. (2003). Intratumoral therapy with cytokine gene-modified dendritic cells in murine lung cancer models. Methods Mol Med. 2003; 75: 711-722.