Cancer Immunotherapy (Coursework Sample)

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Cancer Immunotherapy
Cancer immunotherapy is a cancer treatment type that uses the body’s immune system to battle or combat cancer. Immunotherapy is designed to improve the natural defense of the body to fight cancer cells. This is done by stimulating the body’s immune system to raid the malignant tumor cells culpable for the disease.
Immunotherapy uses materials that have been produced within the body or reproduced in a science laboratory to help refurbish the functionality of the immune system. It works by deterring or gradually slowing down cancer cell growth, stopping the spread of cancer to other body parts or by aiding the body’s immune system boost its effectiveness at getting rid of the cancer cells.
Importance of immunotherapy
Cancer immunotherapy is crucial because;
* It helps fight both the active and dormant metastases and micro diseases.
* It reduces the resistance of the chemotherapy agents.
* It can impact the troublesome hard to kill cells of the cancer stem which bring about the unconstrained growth and production of cancer cells.
* It presents an independent cancer cell killer apart from chemotherapy.
* It helps in the speedy recovery and general outcomes for patients.
1 Immunotherapy for Prostate Cancer Using Manipulation of T Cells Inhibitory and Costimulatory Signals and Antigen 4 Blockade.
Prostate cancer is a neoplastic malignant disease that forms in the prostate tissue glands. Research has shown that prostate cancer is predominant in older men with an estimated 80% of men about the age of 80 diagnosed with it.
Albeit this type of cancer is one of the most prevalent amongst the men of the older generation in America, the identification of probable appropriate and effective immune based treatment has been critically strained by the inadequacy of suitable animals for research. In recent times some of the crucial mechanisms involved in activation and inhibition of the anti-tumour cells have gained recognition.
A novel syngeneic model of Murine prostate has been established to help examine the manipulation intended to bring about an anti-prostate cancer response through the costimulation of the enhanced T cells. Studies have found out that after TRAMPC1 (pTC1), a tumorigenic prostate cancer line cell got from transgenic mice has rejected the C57 BL/6 syngeneic mice but not rejected by the athymic mice. This is after transducing this cell line to express the B7.1 costimulatory gland.
In vivo Antigen 4 blockade, the antigen enhances the responses of anti-prostate cancer immune. The response brought about by Antigen 4 blockade ranges from complete rejection of cells to reductions in growth of these cells. Collectively, the two experiments suggest that the correct manipulation of the T cells inhibitory and costimulatory signals will provide a highly versatile and resilient basis for immunotherapy for prostate cancer. To add on this, the syngeneic murine model earlier introduced provides an exhaustive system to further test the treatment for prostate cancer.
Methods
In manipulation of the T cells inhibitory and costimulatory signals, pTC1 was transduced in a more stable way to express Murine B7 by use of an ecotropic retrovirus that contains the murine gene B.7. For controls, the pTC1 was again transduced with one of the uninhabited vector that lacks the Murine B7 gene. The Murine B7 was thereafter evaluated by staining with CTLA – 4 B7 binding immuno-globin fusion proteins and later followed by conjugated goat antihuman immuno- globin FTC. Flow ctyometry was then executed using the ESP flow cytometer. The tumours raise in the cells were then grown in culture and analysed in isolation.
In using the Antigen 4 Blockade, the cell lines were grown, cultured and maintained. Antigen 4 was then produced, purified and tittered. Concentrations of the antibody were then quantified by the use of UV spectrophotometry (Kwon, Eugene et al). Several experiments were then performed on the metabolism of electrolytes and kidneys. Finally the tissue tissues were analysed by use of the Histopathology (Maurice, Elimination of Residual Metastic Prostate Cancer and Adjunctive Cytotoxic T Lymphocyte Associated Antigen 4 Blockade Immunotherapy after surgery).
Results
When manipulating the T cell inhibitory and costimulatory signals, the cytofluorimetric analysis of the pTC1 cells revealed that there were an estimated 50% to 70% of pTC1 cells that were passed early but they expressed low and detachable MHC molecules of class 1. Further passing of the pTC1 cells could not detect MHC class 11.
Tag mRNA was not apparent in the pTC1 as well as the deritive cells obtained from the tumours and the ones maintained in vitro.
Additionally the results established that the expression of Murine B7 by the prostate cancer cells of the Murine is enough to cause the cancer cell rejection in vivo.
Discussion
The effective transduction of CTLA-4 blockade and the B7 in inducing regression of pTC1 cells that have somehow little or no MHCI is surprising.
Studies show that when pTC1 cells are modified to bring out the B.7 murine costimulatory ligand, an immune host response is triggered leading to rejection of the cells in syngeneic.
The studies clearly show that a host immune response is shown when pTC1 expresses murine B7 and the blockage of CTLA-4 can favour the rejection of the unmodified tumour cells of the prostate by doing away with the inhibitory signals in the pathway of the costimulatory that helps regulate the responses of the T cell.
Through the use of murine model for prostate cancer results have shown that one of any two independent but related sets of T cell costimulatory pathway limbs can be employed to boost the response of the immune against prostate cancer.
2 Gene Therapy for Breast Cancer
Breast cancer is a cancer type that forms in the breast tissues. The commonest type of breast cancer is known as the ductal carcinoma. This one begins in the milk ducts lining. The other type is lobular carcinoma. This one begins in the breast lobules (milk glands). Breast cancer occurs in both male and female although it is predominant in females.
One of the bottlenecks to effective cancer gene therapy is the scarcity of regulatory sequences that target selective gene expression in tumour cells (Sue, Zhao-Zhung, et al. Targeting Gene Expression Selectively in Cancer Cells by Using the Progression-Elevated Gene 3 Promoter). A lot of specific tissue promoters may be recognized but only a limited number of cancer selective gene promoters are actually accessible. The PEG-3 or Progression Elevated Gene is a gene rodent determined by subtraction hybridization. The PEG promoter displays in a large spectrum the expression cancer cells in humans with significant expression in the counterparts of the normal cellular. The efficacy of PEG promoter as a block regime for cancer gene therapy has been further proved in vivo experiments. In the experiments, the PEG promoter controlled the expression of a gene that completely inhibited the growth of cancer in nude mice. The compelling conclusions after observations has clearly indicated that the PEG promoter together with its specific cancer expression has the means of delivering selected genes to the cancer cells therefore providing a very vital component in developing therapies for cancer genes.
Getting rid of cancer especially in situations where the tumour cells have got metastatic potential has proved to be an unsuccessful endeavour even in situations where combined therapeutic approaches such as radiotherapy, chemotherapy and surgery have been used. Even with such valid therapeutic approaches, the rate of cancer relapse is significantly high. Such observations correctly indicate the need for more innovative modalities for treatment of cancer. Gene therapy for cancer is one of the approaches that if combined with appropriate effective improvements will provide reliable treatment for cancer. The application of cancer gene therapy has used several strategies with one of them being the use of overexpression and replacement of suicide genes as well as tumour suppressors.
PEG-3 or Progression Elevated Gene was cloned from a tumour model on the basis of embryo cells of a rat.
Methodology
Normal cells of human prostate epithelial and prostate carcinoma were cultured. Normal human mammary immortal epithelial cells plus normal cells of human epithelial and cells of breast cancer were cultured. Human glioma malignant cell lines and primary human fetal astrocytes were cultured as well. The cultures above were all maintained in a humidified air incubator.
Next the PEG-3 promoter was cloned into a PGL-3 which is a basic vector to come up with mutant constructs that contain mutation. Sequence PEA -3 or AP-1. Two replication Ads were created. One was for the experiment and the other one as a control. RNA was then extracted and the Northern blot performed. Preparation of whole cell lysates was done and Western blotting performed. Extraction of nuclear extracts was done and later EMSA was performed. After this there was analysis of DNA fragments. Tumorigenicity studies were conducted and animals were monitored round the clock for any formation of tumour. Later on the tumour volumes were determined. All experiments were repeatedly d...