miércoles, 19 de diciembre de 2018

Activation Immunotherapies

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Immunotherapy is a disease treatment that works by initiating, improving or suppressing the body’s immune response. An activation immunotherapy is one that either induces or amplifies an immune response. This type of therapy may be used to treat cancer or create vaccines. A suppression immunotherapy, on the other hand, reduces an immune response and this is used to treat autoimmune disease, allergy and to prevent transplant rejection.

Dendritic cell based immunotherapy

Dendritic cells or DCs are potent antigen-producing cells that can sensitize T cells to both new and recall antigens. The goal of DC based immunotherapy in cancer is to prime specific antitumor immunity by generating effector lymphocytes (e.g. CD4+ T cells and CD8+ T cells) that target, attack and destroy tumors.

DCs as vaccines for cancer

The first attempt to use DCs as human cancer vaccines was made at Stanford University. DCs were isolated from patients with non-Hodgkin’s lymphoma that had failed to respond to chemotherapy. The patients’ DCs were loaded with immunoglobulin idiotype taken form their tumors. These antigen loaded DCs were then re-administered to the patients via injection. This resulted in most of the patients developing a T cell mediated immune response to the tumor specific antigen. Of the first six patients to be treated, two experienced full remission. Since then, larger numbers of patients with non-Hodgkin’s lymphoma have been treated with idiotype-pulsed DCs and the effectiveness of this approach has been confirmed. Pilot clinical trials have also been carried out to test antigen-pulsed DCs as a treatment in various forms of cancer including colorectal, prostate and non-small cell lung cancer. The results have shown that antigen-loaded DC vaccinations may provide a promising immunotherapy for treating a wide range of cancers.

Sipuleucel-T (Provenge)

To date, the only DC vaccine that has been approved by the Food and Drug Administration as a cancer immunotherapy is Sipuleucel-T, known commercially as Provenge. The drug is used to treat cases of advanced prostate cancer, where hormonal therapy is no longer helping. This vaccine involves immune cells being taken from the patient’s blood and sent to a lab where they are turned into dendritic cells and exposed to prostatic acid phosphatase, the presence of which triggers an immune response against prostate cancer cells. The DCs are then infused back into the patient. This is repeated on two more occasions, separated by two weeks, meaning the patient receives three doses of the DCs overall. This vaccine has been shown to help increase patient survival by several months. Researchers are now investigating whether the vaccine can be used to help men with less advanced prostate cancer.

Other vaccines

Many types of cancer vaccine have shown some promise in clinical research trials, but have not yet received FDA approval as cancer therapies.

T cell based adoptive immunotherapy

Another immunotherapy technique that harnesses a patient’s immune system in order to combat disease is adoptive cell therapy (ACT). This involves engineering a patient’s T cells so that they can recognise and attack cancer cells. T cells are collected from the patient’s blood and then genetically engineered to produce cell surface receptors referred to as chimeric antigen receptors (CARs). CARs enable the T cells to recognize specific antigens present on the surface of cancerous cells. This population of CAR T cells is expanded in the laboratory until it numbers in the billions and then it is infused into the patient. The T cells then multiply in the body and by using their genetically engineered receptor, they attack cells that present the tumor specific antigen on their surface.

Although ACT has so far only been carried out in small clinical trials, the treatment has resulted in some remarkable responses in patients with advanced forms of cancer. Several early stage trials of ACT in patients with advanced acute lymphoblastic leukemia (ALL) have resulted in many cancers completely disappearing, with several patients having remained cancer free for long periods. Similar promising results have been observed in trials of lymphoma patients.