Paper Critique
“Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients”
Dendritic cells are antigen presenting cells that stimulate the adaptive immune response by presenting antigens to the T cells. They are derived from hematopoietic bone marrow progenitor cells as immature dendritic cells. These immature dendritic cells have pattern recognition receptors like toll like receptors that recognize specific chemical structures of foreign antigens or non-self-antigens. Once the immature dendritic cells recognize foreign molecules they drain to the lymph nodes as mature dendritic cells and present these antigens in form of a peptide-major histocompatibility complex to naïve T and B cells for activation of the
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It has been found that the anti-tumor response depends on the presentation of tumor antigens by dendritic cells. Tumor cells are poor antigen presenting cells and thus fail to elicit a potent anti-tumor immune response. Tumors can also prevent antigen presentation by a variety of mechanisms. Tumors can cause monocytes to differentiate to macrophages rather than dendritic cells and thus prevents the priming of tumor-specific T cells by dendritic cells. Tumors-derived factors can also alter the maturation of dendritic cells and cause a switch in DCs to become pro-tumorigenic. Another mechanism by which tumors evade stimulation of an anti-tumor immune response is by production of IL-10 which inhibits the DCs maturation.
Many researchers are currently studying immunotherapy by vaccination to elicit an effective anti-tumor immune response to delay or eliminate tumor progression. The aim of this therapy is to elicit CD8+ T cells that recognize the peptide-MHC class 1 molecule on the tumor antigens and cause tumor cell death by increase secretion of granzyme and perforin. For an ideal anti-tumor immune response atleast 4 components of the immune system need to be present: appropriate mature dendritic cells; activation of CD4 T cells, elimination of T regulatory cells; and inhibition of the immunosuppressive immune
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Treatment includes surgery, radiation therapy, and chemotherapy. The first stage of treatment involves surgery, following which patients receive radiation along with temozolomide chemotherapy. Temozolomide works by causing DNA alkylation and subsequent tumor cytotoxicity as well as sensitizing tumor cells to radiation. These treatments only increase survival for a few months. Treating GBM is difficult because the tumor cells become resistant to temozolomide. This causes recurrence of GBM, which is very aggressive. Most drugs do not cross the drug brain barrier, thus limiting the treatment options once resistance to temozolomide occurs. Thus, there is an increasing need for alternate treatments to treat
The research presented in Jedd D. Wolchok “Cancer’s Off Switch” examines two different forms of immunotherapy used to treat cancer cells by boosting the patient's own immune system defenses. The article provides a comprehensive history of the scientific discoveries and previous research that lead to the immunotherapy treatments, specifically the different levels of the immune system. In addition, the article addresses two different methods of immunotherapy currently in testing in clinical use. The research is educationally significant because it focuses on the body's internal defense system and attempts to disable the brakes cancer cells enforce on the immune system, which has shown progress in both tumor size regression and improvements in
In other words, it specifically triggers immune responses pertaining to the mesothelioma malignancy or targets the cancer cells at hand. Active immunotherapy excites an immune response by presenting antigens to the immune system for a response against the malignancy itself. Although the mesothelioma malignancy has a unique set of cells, the tumor does not always produce antigens. This results in the use of an antigen precursor protein called Mesothelin, which allows these antigens to form around the tumor in hopes to specifically target the malignancy site. On the other hand, passive immunotherapy does just the opposite. Passive immunotherapy does not induce an immune response; it simply and directly targets the malignancy by injecting “immune compounds that attack the cancer such as antibodies, cytokines, T cells and macrophages” (Selby). Non-specific immunotherapy injects cells that inhibit the growth of the tumor cells, preventing those cells from constant reproduction. These cells that are injected cooperate directly with the malignancy and are known as cytokines, lymphokine-activated killer cells and macrophages. Immunotherapies such as active, passive and non-specific passive all are becoming effective therapies for mesothelioma and are indicative of improving the patient’s
Dendritic cells use chemokines to find their way to the lymph node. T-cells originate in the bone marrow from hemopoetic stem cells along with B-cells. When T-cells receive the notch signal, they migrate to the thymus where they mature. T-cells go through V(D)J recombination then preTCR go through VJ recombination. Eventually they make it to positive selection which selects for MHC restricted cells and then negative selection where self-reacting cells are eliminated. Net is when the T-cells either become helper cells or cytotoxic
Vaccine provokes our bodies to produce immunity by triggering our immune system to create antibodies (a substance that fights diseases). The vaccine encourages the immune system to produce its own antibodies, which is called “active immunity” as though the person has already infectected by the disease. And once, the vaccinated person has the disease, the immune system will immediately recognize that it is time to produce antibodies. 1
Helper T-cells (CD4+) interact with antigen fragments of MHC 2 class molecules on the surface of antigen presenting cells and when activated secrete cytokines that stimulate other lymphocytes. Cycotoxic T cells (CD8+) bind to MHC 1 class on infected host cells and secrete proteins that initiate destruction.
The TIL’s that strongly exhibit the ability to recognize a patients tumor cells are selected to be grown in large quantities in a laboratory then activated by cytokines and infused back into the patient. The ex vivo lymphocytes reinserted back into the bloodstream are accompanied with growth factors to help ensure the cells survival and expansion. In comparison to other forms of immunotherapy, ACT can provide several advantages for their application such as only a small number of TIL’s are needed to be identified then expanded for treatment as well as tests done in vitro can determine the precise populations and functions needed for cancer regression. The ability to manipulate a host’s environment before reinfusing activated T lymphocytes, providing an ideal environment for those transferred cells, also provide a significant
We hypothesized that administration of EXO/SEB bearingtumor antigen (Ag) or an anti-tumor component like PRP or NLX might generate a more effectivetumor immune response, via a mechanism involving the induction of an anti-tumor Th1 response.
Immunotherapy is a newer form of cancer research in which the treatments allow the immune system to detect and attack the cancer cells. According to the National Cancer Institute website, immunotherapy is a newer form of cancer treatment, which is being used in many different ways to target the multiple forms of cancer, as treatments may vary from patient to patient though they have the same type of cancer. One method of immunotherapy uses medicine to stop the release of certain proteins that would otherwise stop the immune system from attacking the cancerous cells. This method is used with tumours that secrete these proteins that normally stop the immune system from attacking healthy cells. Another method of immunotherapy, called adoptive
There are about three common immunotherapies, which are: hybrid, passive or active. Immunotherapy operates under the scientific facts that lays out that cancer cells contain molecules that are attached onto their surface which the immune system can detect. In active immunotherapy, tumor associated antigens (TAAs) are directed at the cancer cells and they begin attacking them. Passive immunotherapy works by enhancing anti-tumor responses by the use of monoclonal antibodies, cytokines, and lymphocytes. In some cases, immune cells are transferred from the body of the patient, cultured, and returned to the body to attack the cancer cells (Collins, 2009). This form of cellular therapy commonly uses and dendritic cells and cytotoxic T-cells.
The Purpose of cancer vaccines is to stimulate the body’s defenses against by increasing the response of the immune system. and what this basically means is that it improves/speeds up the cells and tissues and organs that work together to protect your body against sickness. your immune system provides a protective system against diseases such as foreign pathogens and from abnormal body cells and without it working properly you are exposed to different types diseases and that is not good for your overall health.
By combining the power of antibodies with the cancer-destroying abilities of cytotoxic drugs, these therapies can generate better results than flooding the body with systemic chemo treatments that often generate unpleasant side effects that include killing healthy tissue.
Cancer patients (e.g. glioblastoma) are typically immunosuppressed. This appears to be a survival strategy of the more aggressive tumors and is in excess of that which would be expected by external factors e.g. chemotherapy, malnutrition, steroid use. Immunotherapy seeks to counter this by improving the body’s immune response to a tumor. Currently, the principal mechanisms employed are: 1) to improve an aspect of the immune response (e.g. T-cell activation) and 2) to encourage the targeting of particular antigens. The latter is typically achieved by exposing the immune system to the antigen in question, in vivo, or in vitro followed by re-introduction of the primed cells to the body. The clinical relevance of this approach has already been demonstrated for solid tumors such as melanoma and prostate cancer. Tumors of the nervous system remain a particular challenge in that their location is relatively ‘immune privileged’. We present a summary of progress in this area.
Immunology basically involves understanding the immune system and how it responds to various disease conditions. the immune system consists of a number of components. Traditionally, it is divided into humoral and cellular immune responses. It can also be distinguished into innate and adaptive immunity. The innate immunity can discriminate between normal tissues , self and newly encountered non-self-proteins while the adaptive immunity is the more complex system aimed at the eradication of intracellular pathogens. To do this, antigen derived from such pathogens that are often new to the host organism, need to be recognised by receptor-bearing specialised immune cells which respond to a complex system of stimulatory and costimulatory signals. Better understanding of the human immune system has led to the identification of a number of tumor-associated antigens in the 1980s and the development of various immunotherapeutic approaches. In recent years, identification of the specific antigenic MHC class I epitopes, advancements in genetic engineering, gene delivery, and cell-based therapeutic approaches allowed development of the novel immunotherapeutics.
This original research focuses on defining cancer immunotherapy and the different types of immunotherapy that has received regulatory approval within the past twenty-five years. Cancer immunotherapy also known as biotherapy is "the manipulation of the immune system, or utilization of components of the immune system, as the cancer treatment." After a brief history of immunotherapy and the foundation of its origin is given in the introduction Dillman goes into detail about the different types of immunotherapies. The different types of immunotherapies include nonspecific immune stimulants Bacillus Calmette-Guerin (BCG) and Levamisole which are drugs used to boost the immune system in a general way. Cytokines are the messengers of the immune system; interferon-a and interleukin-2 are cytokines used to mediate and regulate immune responses, inflammation, and hematopoiesis which is new blood cell formation.
Immunotherapy: This treatment makes use of certain vaccines, antibodies, and growth factors to restore or boost the patient’s immune system to effectively fight against cancer.