What are the Major Cancer Therapies Based on Immune Sytem?

(a) Antibody or monoclonal therapy:

Antibody therapy can be used in a variety of ways to treat cancer. Monoclonal antibodies act through Antibody- Dependent Cell-Mediated Cytotoxicity (ADCC) or Complement-Dependent Cytotoxicity (CDC).

Conjugated monoclonal antibodies with a toxin or a radioisotope (Radioimmunotherapy) can be used in the treatment because the antibody conjugate is absorbed into the cell itself; resulting in cell death. The chemotherapeutic agent can be taken directly into the targeted malignant cell, rather than being systemically absorbed with the help of antibodies. There are a number of antigens and corresponding monoclonal antibodies for the treatment of B cell malignancies.

Compared to hematologic malignancies, solid tumors do not have as many specific targets for monoclonal antibodies that are not cross-reactive with antigens on normal tissues.

Two significant monoclonal antibodies used in solid tumors treatment are “edrecolomab” and “trastuzumab”. Edrecolomab (trade name Panorex) is a chimeric mouse/human monoclonal antibody to the cell-surface glycoprotein expressed on epithelial tissues and on various carcinomas.

Preliminary studies had shown promise of a possible use in patients with stage III colorectal carcinoma. Trastuzumab (Herceptin) is a monoclonal antibody that interferes with the HER2/ new receptor. HER2/new receptor regulates cell growth, survival, adhesion, migration, and differentiation.

The defective HER receptor proteins stuck in the “on” position in certain cancers, notably in some breast cancers. Trastuzumab antibody binds and blocks the receptor for receiving further signals to stop uncontrolled cell growth

Cytokines and Cancer Therapy:

Cytokines are the messengers of the immune system. Cytokine therapy involves the administration of signaling molecules (usually proteins) that increase the maturation and growth of antigen presenting cells and T cells. IL-2 and interferon-alfa 2b are two cytokines approved for treatment of cancer.

IL-2 has demonstrated activity against renal cell, melanoma, lymphoma, and leukemia. Interleukin-2 (IL-2) is a T cell growth factor that binds to a specific tripartite receptor on T cells. Interferon has activity in the same histology’s but also in Kaposi’s sarcoma, chronic myelogenous leukemia, and hairy cell leukemia. Interferon alfa has many roles. It upregulates genes like MHC class I, tumor antigens, and adhesion molecules. It is also an anti-angiogenic agent. It is extremely active in the immune system, promoting B and T cell activity.

Interferon alfa can stimulate macrophages, even dendritic cells, and upregulates Fc receptors. Overall, cytokines are substances that appear to have application in the treatment of hematologic malignancies or immunogenic tumors.

Vaccine Approaches against Cancer

Efforts to treat cancer with vaccines date back to the origins of immunology.

Recent research has indicated that the vaccines are also useful in the prevention and treatment of cancer. Different types of vaccines are developed to treat different types of cancers. For example, new vaccines against the human papilloma virus (HPV) prevent women from getting cervical, vaginal, and vulvar cancer, and vaccines against hepatitis B virus (HBV) may lower risk of getting liver cancer in some people (Refer Chapter 18 for vaccines).

Advances in immunotherapy

The development and testing of second generation immunotherapies are already under way. Antibodies targeted to disease-causing antigens can be effective under certain circumstances, but in many cases their efficacy may be limited by other factors.

To overcome this problem, cytokines are conjugated to them to trigger an immune response. Engineering the antibody in such a way that the conjugated cytokines get separated after entry into a cell by endocytosis can potentially increase the efficacy.

Therapeutic administration of certain conjugated cytokines may cause systemic inflammation, resulting in serious side effects and toxicity. Hens a new generation of chimerical molecules such as artificial T cell receptor, containing an immune-stimulatory cytokine attached to an antibody can target the cytokine’s activity to a specific environment such as a tumor, and are able to generate a very effective yet localized immune response against the tumor tissue.

Use of immune cells cloned from patients immune system is a new immune therapy in cancer treatment. US doctors from the Clinical Research Division led by Cassian Yee at Fred Hutchinson Cancer Research Center in Seattle treated a skin cancer patient for the first time successfully by this method.