Activation Immunotherapies

Cancer

Cancer immunotherapy attempts to stimulate the immune system to reject and destroy tumors. BCG immunotherapy for early stage (non-invasive) bladder cancer utilizes ''instillation'' of attenuated live bacteria into the bladder, and is effective in preventing recurrence in up to two thirds of cases. Topical immunotherapy utilizes an immune enhancement cream (imiquimod) which is an interferon producer causing the patients own killer T cells to destroy warts,, actinic keratoses, basal cell cancer, vaginal intraepithelial neoplasia., squamous cell cancer, cutaneous lymphoma, and superficial malignant melanoma. Injection immunotherapy uses mumps, candida the HPV vaccine, or trichophytin antigen injections to treat warts (HPV induced tumors). Lung cancer has been demonstrated to potentially respond to immunotherapy.

In many parts of Asia, Medicinal mushrooms are thought to be able to boost the immune system naturally.

Cellular and animal research has shown that ''Agaricus blazei'' may stimulate immune system cells and the production of interferons and interleukins (reviewed by G. Hetland). Mushroom isolates like PSK also are used to increase immune system parameters (reviewed by Kobayashi). Used in conjunction with chemotherapy, PSK has increased the survival time of cancer patients in randomized, control studies, with a variety of cancer types.

Dendritic cell based immunotherapy

This utilizes dendritic cells to activate a cytotoxic response towards an antigen. Dendritic cells, an antigen presenting cell, are harvested from a patient. These cells are then either pulsed with an antigen or transfected with a viral vector. The activated dendritic cells are then placed back into the patient; these cells then present the antigens to effector lymphocytes (CD4+ T cells, CD8+ T cells, and in specialized dendritic cells, B cells also). This initiates a cytotoxic response to occur against these antigens and anything that may present these antigens. One use for this therapy is in cancer immunotherapy. Tumor Antigens are presented to dendritic cells, which cause the immune system to target these antigens, which are often expressed on cancerous cells. The Dendreon product candidate Provenge is one example of this approach.

T cell based adoptive immunotherapy

Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes is an effective treatment for patients with metastatic melanoma; this is based on adoptive immunity.

ACT uses T cell-based cytotoxic responses to attack cancer. T cells that have a natural or genetically engineered reactivity to a patient's cancer are expanded, made more effective, ''in vitro'' using a variety of means and then adoptively transferred into a cancer patient.

For example, T cells with a naturally occurring reactivity to a patient’s cancer can be found infiltrated in the patient's own tumors. The tumor can be harvested, and these tumor-infiltrating lymphocytes (TIL) can then be expanded, or made more effective, ''in vitro'' using high concentrations of interluekin-2 (IL-2), anti-CD3 and allo-reactive feeders. These T cells can then be transferred back into the patient along with exogenous administration of IL-2 to further boost their activity.

Thus far, a 51% objective response rate has been observed; and in some patients, tumors shrank to undetectable size.

The initial studies of ACT using TIL, however, revealed that persistence of the transferred cells ''in vivo'' was too short. Before reinfusion, lymphodepletion of the recipient is required to eliminate regulatory T cells as well as normal endogenous lymphocytes that compete with the transferred cells for homeostatic cytokines. Prior lymphodepletion to transfer of the expanded TIL was made by total body irradiation. The trend for increasing survival as a function of increasing lymphodepletion was highly significant (P=0.007).

Morgan ''et al.'' (2006) demonstrated that the adoptive cell transfer of lymphocytes transduced with retrovirus encoding T cell receptors (TCRs) that recognize a cancer antigen can mediate anti-tumor responses in patients with metastatic melanomas.

In such T cell genetic engineering, TCRs that have been identified to have reactivity against tumor-associated antigens are cloned into a replication-incompetent virus 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. The Surgery Branch of the National Cancer Institute (Bethesda, Maryland) is actively investigating this form of cancer treatment for patients suffering aggressive melanomas.

Combination of ACT with such genetic engineering of T cells has opened possibilities for the extension of ACT immunotherapy to patients with a wide variety of cancer types and is a promising new approach to cancer treatment. The patient was free from tumours within eight weeks of treatment. Dr. Cassian Yee described the research findings at The Cancer Research Institute International 2008 Symposia Series. Responses, however, were not seen in other patients in this clinical trial.

Larger trials are now under way. [http://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2008/06/18/scicanc118.xml] immunotherapy, which includes vaccination, involves activating the immune system to respond to an infectious agent.

Further Reading


This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Immunotherapy" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.

Last Updated: Feb 1, 2011

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