Cancer immunotherapy: active immunotherapy/up-regulation
Cancer immunotherapy attempts to stimulate the immune system to reject and destroy tumors. Proleukin™ (recombinant human IL-2 protein) is approved for the treatment of melanoma and renal cell carcinoma. Topical immunotherapy using an immune enhancement cream (imiquimod), which is an interferon producer, can result in the patient's own killer T-cells destroying warts, actinic keratoses, basal cell cancer, squamous cell cancer, cutaneous lymphoma, and superficial malignant melanoma.
Limitations: Proleukin induces strong systemic toxicities.
Dendritic cell based immunotherapy: active immunotherapy/up-regulation
This technology utilizes dendritic cells to activate a cytotoxic T-cell response towards an antigen and is used by such company's as Dendreon. Dendritic cells are antigen-presenting cells that can be harvested from a patient. In the laboratory, these cells are then pulsed with an antigen or transfected with a viral vector or plasmid encoded to express an antigen. The activated dendritic cells are injected back into the patient where the antigens are presented to effector lymphocytes (CD4+ and CD8+ T-cells). This therapy initiates a cytotoxic response against these antigens and any cells that may present these antigens. This approach can be used to cause the immune system to target tumor antigens such as PSMA, Her-2, hTert and CEA.
Limitations: Because much of this procedure occurs outside the body, this ex vivo process is laborious and expensive.
T-cell based adoptive immunotherapy: passive immunotherapy/up-regulation
This therapy uses T-cell-based cytotoxic responses to attack cancer. In brief, T-cells that have a natural or genetically engineered reactivity to a patient's cancer are expanded in the laboratory and then transferred into a cancer patient. In the case of engineered T-cells, T-cell receptors (TCR) that have been identified to have reactivity against tumor-associated antigens are cloned into a replication-incompetent virus (unable to replicate) that is capable of genomic integration. A patient's own lymphocytes are exposed to these viruses and then expanded non-specifically or stimulated using the engineered TCR. The cells are then transferred back into the patient. This therapy has been demonstrated to result in objective clinical responses in patients with refractory stage IV cancer. Objective clinical responses up to 51% have been observed in some studies. The National Cancer Institute is actively investigating this form of cancer treatment for patients with melanomas.
Limitations: This technique is limited to experimental centers, is labor intensive and expensive and is not suitable for packaging as a pharmaceutical product.
Vaccination: active immunotherapy/up-regulation
Active immunotherapy for the prevention or treatment of infectious agents is generally known as vaccination. Traditional vaccination involves activating the immune system to respond to protein antigens of a live or weakened pathogen without causing the disease of the pathogen. DNA-based immunotherapies are engineered to produce these selected antigens or immune-enhancing cytokines from engineered pieces of DNA using the body's own synthetic capacity. An example of this approach is a plasmid-based HCV vaccine, currently in clinical studies using Inovio's DNA delivery technology. DNA vaccines are engineered to cause cells in the body to produce antigens associated with a cancer or pathogen in order to stimulate an immune response against cancer cells or cells infected by an infectious disease.
Limitations: One must select the proper antigen to get a clinical benefit from these vaccines. While they are good stimulators of T-cells, unlike conventional vaccines, the choice of antigen to target is not always obvious.
Suppression: passive immunotherapy/down-regulation
Immune suppression dampens an abnormal immune response in autoimmune diseases or reduces a normal immune response to prevent rejection of transplanted organs or cells.
Allergies: active immunotherapy/down-regulation
Allergy treatments such as antihistamines or corticosteroids treat only the symptoms of allergic disease. Immunotherapy is the only available treatment that can modify the natural course of the allergic disease by reducing the immune system's sensitivity to allergens. A series of small doses of allergen (allergy shots) can induce an immune tolerance to the offending agent.