Active and Passive Immunotherapy of Cancer and Vaccines - Coursework Example

IMMUNOTHERAPY 29th September, 2008 TABLE OF CONTENTS 1. EXECUTIVE SUMMARY…………………………………………………3.0 2. INTRODUCTION…………………………………………………………. 3.0 3. ACTIVE AND PASSIVE IMMUNOTHERAPY…………………………. 4.0 4. PAST, PRESENT AND FUTURE RESEARCH AND DEVELOPMENTS IN IMMUNOTHERAPY……………………………………………………… 5.0 5. CANCER IMMUNOTHERAPIES AND VACCINES……………………. 6.0 6. CASE HISTORIES………………………………………………………… 7.0 7. CONCLUSION……………………………………………………………. 10.0 8. BIBLIOGRAPHY……………………………………………………………11.0 EXECUTIVE SUMMARY Immunotherapy is considered to be a prime treatment imparted for the cancer patients Invention of various vaccines have turned the public health image into a positive frame by preventing the development of numerous infectious diseases but vaccines against cancer are still a challenge to be overcome, however the current studies and development in the medical field has focused mainly on the advancements in the areas of immunotherapy helped in the development of more reliable and effective vaccine strategies. The following report emphasizes on the past, present and future strategies and development of immunotherapy along with the analyses of the past case studies where immunotherapies have been applied to assist in the treatment of a medical condition and their corresponding effects on the patient's condition INTRODUCTION Immunotherapy of cancer was basically originated through Dr William Coley about 100 years ago who proved that he could control the growth of some advanced stage cancers through Coley’s toxin which is a blend of vaccines. Cancer immunotherapy is one that harnesses the individual’s self defence mechanism to fight with the cancer cells. When cancer prevails in a body, the gap between the affected cancer cells and the non affected ones becomes too narrow; hence the healthy cells are overpowered by the cancer cells. Cancer immunotherapy induces molecules in a body so as to awaken the immune system and respond to the cancer cell. So far two main approaches in the cancer immunotherapy have been developed, firstly the antigen specific approach and secondly the whole cell approach. The first approach is related to particular antigen that encourages an immune reaction for a particular type of tumour. However, if the diagnose of the appropriate antigen is incorrect, the results may lead to lesser affectivity. An antigen related approach requires only the patients dendritic cells cell, on the other hand whole cell approach involves the entire cancerous cells rather than specific antigens because such approach augments the immune response , Cell Genesys is an organization involved in the development of a complete vaccine approach in regard to its GVAXR cancer immunotherapies. ACTIVE AND PASSIVE IMMUNOTHERAPY Immunotherapy for cancers is applied on an individual so as to generate immune responses against tumor cells. Recent developments have led to the invention of active and passive immunotherapy as effective therapeutic strategies (Waldman A T, 2003). Active immunotherapy was founded by Paul Ehrlich and William Coley in 1890s, which has been effective against agents that result in acute self-limiting infectious diseases followed by immunity while Passive immunotherapy has come of age and is highly successful. For over two centuries, active immunotherapeutic approaches has been the major highlight for prevention of diseases but it is also seen that active immunotherapy has been less effective against cancer where body agents find ways to escape normal immune responses but the current researches such as identification of tumor rejection antigens, viral antigens in cancers associated with viruses, and tumor-specific differentiation antigens have made the application of active theory more successful. Efforts to enhance the efficacy of vaccines have focused on both the function of APCs such as dendritic cells and the activation of T cells. Various immunotherapeutic approaches have been developed since over 90 years like systemic administration of cytokines; therapeutic vaccines based on tumor cells or dendritic cells; adoptive immunotherapy etc The results also show that there are a number of obstacles that prevent effective immunotherapy of cancer such as tumor-cell which result in the loss of class I MHC expression and failure to maintain the co-stimulatory B7 molecules (Waldman A T, 2003). After decades of futile research in passive immunotherapy which was initiated by Emil Roux and Alexandre Yerson in 1888 by isolating the toxin from the diphtheria bacterium followed by the development of monoclonal antibodies by Köhler and Milstein, now are emerging as useful immunotherapeutic strategies. It is hoped that such immunizations would help in clinical application attacking epithelial new formations, particularly carcinoma by means of specific anti-epithelial sera (Waldman A T, 2003). Passive immunotherapies utilize large doses of infused antibodies which circulate throughout the bloodstream, binding to antigens on targeted cells and destroying them. For example the treatment of B-cell non-Hodgkin's lymphoma is through passive immunotherapy involving Rituxan that helps in prolonging the clinical response from one to three years of time. PAST, PRESENT AND FUTURE RESEARCH AND DEVELOPMENTS IN IMMUNOTHERAPY: PAST, PRESENT AND FUTURE RESEARCH AND DEVELOPMENTS IN IMMUNOTHERAPY: In 1900, Paul Ehrlich suggested that molecules that react with tumors could act as a key factor in treatment of cancer highlighting the antibody mediated passive immunotherapy. In 1988- 1991, the methodology for isolating tumor antigens recognized by CTLs was introduced. With the progress of time, tumor rejection antigens were identified, the functions of APCs was enhanced by inducing the maturation of dendrite cells, signal I and signal II were augmented, cytokines were introduced into vaccine preparations, and surrogate assays were developed for effectiveness of the vaccines. Potential interventions were applied to prevent obstructions or blockade of negative immunotherapy mechanisms which deteriorated the entire process. New approaches to the production of monoclonal antibodies have been initiated. CANCER IMMUNOTHERAPIES AND VACCINES Cancer is one of the eminent leading causes of death world wide. In recent years it has become imperative that the numbers of people who die due to cancer are almost equivalent to those who live along with it. The immunotherapies in use are not fully safe and effective due to which therapeutic approaches have been chosen for further research into the field of immunotherapy. Such techniques augment the body capacity to overcome the effects produced by the unhealthy cancer cell. Anti cancer drugs have actually been able to develop the preventive measures against cancer. Vaccines for cancer immunotherapy such as Pipeline Analysis, CHI Insight Pharma report, surveys and assesses recent developments are a successful move towards the treatment of cancer (CHI Insight Pharma Reports, 2006). Cancer vaccines comprise of cancer related material called as to increase the response rate against the antigens. The past decades have noticed a challenge to develop antigens that could improve a patient’s immune system to fight the disease effectively. One of the most interesting new approaches developed is dendrite cell vaccine which activates a body’s immune system. Cancer Immunotherapies may result in higher life quality during the course of the medical treatment. Idiotype vaccines are continuously used for the cure of lymphoma patients. In advanced melanoma, numerous vaccines are applied resulting in positive status to turn on the immune response system of the body. (Park W J, Christopher C. Benz, 2007). Combination of modern therapies with the traditional methods for instance radio therapy, chemotherapy etc can reform the old methods into contemporary medical practices which have increased effectiveness in the long run. CASE HISTORIES A 45 year old female patient’s complaint of a back mole on her leg which showed some changes over a period of time. There was no sign of previous medical history of the patient regarding melanoma etc. but after her medical examination, an 8 mm * 10 mm erratic brown papule was found. Symptoms of melanoma are common such as asymmetry, border irregularity, colour change, diameter greater than 6mm etc, in this case a proper 5immunotherapy was involved in diagnosing the problem of melanoma (Amor Khachemoune; Eric Ehrsam, 2005). In a case presented by Hoffman K, Marten A, Lindel K, Fritz S, Jager D, Buchler W, Schmidt J 2006, a patient with adenocarcinoma of the pancreas was intervened through a radiation and chemotherapy using combination of Cisplatin, 5-Fluorouracil and interferon .Till date for the treatment to malign tumors, a combination of chemo- and immunotherapy is used especially for the areas such as in head and neck, renal, bladder, esophageal and pancreatic cancer. As a result acute hypocalcemia occurred showing signs of renal failure within a couple of days which required extensive treatment in future. The case recommends the use of intensive electrolytes monitoring and prophylactic treatment of patients. According to E Elkord, 2007, procedures that lead to the impairment of the immune response to promote tumor progression are quite prominent. Such mechanisms reduce the ability of antigens to support an active immune response, in such cases immunotherapy augments the tumor-specific T-cell responses in different cancers including prostate. According to the author, clinical trials in advanced Prostate Cancer patients, immunotherapy has been able to generate positive responses. As per the National Cancer Institute Monographs, a review was consolidated after studying almost 1000 patients under observation, which highlighted the regression of advanced cancer mainly hypernephroma, neuroblastoma, malignant melanoma and melanoma, chorionic cancer which counted almost 60 percent of the cases. The reasons identified for the spontaneous regression was facts in immune responses to tumors; immunological events during tumor progression. In a research conducted by Riker I A, Radfar S, SuHu Liu, Wang Y & T Khong T H, 2007, it was found that the use of conventional oncologic criteria for clinical tumor response was only 2.6%. On the other hand by combining the clinical outcomes of patients with metastatic melanoma worldwide who have participated in an immunotherapy trial that was 35 trials and 765 patients, the response rate increased to 3.3% only. As per the clinical trial conducted a new approach to the immunotherapy of melanoma involved the use of autologous dendritic cells which were able to interact with other immune cells resulting in the activation of an antigen specific immune response but the overall clinical outcomes were disappointing. The effort put in emphasized on the identification of gene signatures that had crucial role in the development of targeted immunotherapies for patients with metastatic disease. 6 the treatment given to melanoma patients have not resulted in positive figures, hence Interferon is been advised as an effective intervention for advanced stage III melanoma patients. Immunotherapy for melanoma has involved varied strategies with different vaccines such as 6DNA, antibodies etc. Kim J C, Dessureault S, Gabrilovich D, Reintgen S D, Slingluff L C, 2002. In a study conducted by Sato S, Iwasaki K, Torisu M, 1992, a 32 year old man was reported with primary linitis plastica of the rectum which was inoperable due to its widespread, after the immuno chemotherapy induced to the patient it was found that the tumor size was reduced due to which a pelvic exenteration was performed which further resulted in an extended life period of 20 months. Fifty-eight patients with Dukes' C classification of carcinoma of the large bowel were placed on immuno- or chemo immunotherapy with Bacillus calmette guerin (BCG) following primary and definitive surgery, and were followed for up to 21 months. The results displayed that the survival of the patients on 5-FU plus BCG improved CONCLUSION Immunotherapy is study of the individuals own self defence system that facilitates the process of recovery from many illnesses. It is been noticed that research and development efforts are carried by many organizations which are continuously struggling to come out with some safe and effective approach to cancer treatments. The field of cancer immunotherapy has rapidly progressed in the last two decades in the generation of recombinant molecules and understanding of molecular immunology especially for the patients suffering with metastatic melanoma and metastatic kidney cancer. It has been observed that patients who undergo cellular vaccines develop antibodies which multiply the tumor antigens, this opens up the potential areas where immunotherapy development may be carried out in the future. Immunization strategies help in identifying the cancer antigens and the current researches are focusing on methods which help to combat the immune attack. New possibilities for developing effective cancer immunotherapies for the treatment of cancer patients are currently being identified. BIBLIOGRAPHY 1. Thomas A. Waldmann, 20th March 2003, Immunotherapy: Past, Present and Future, Nat Med 9(3):269-277, 2003. © 2003 Nature Publishing Group 2. CHI Insight Pharma Reports, November 1, 2006, Cancer Immunotherapies and Vaccines: Pipeline Analysis and Competitive Dynamics, 212 Pages - Pub ID: CHI1394277, , http://www.marketresearch.com/product/display.asp?productid=1394277&g=1 3. Sato S, Iwasaki K, Torisu M, 1992, A case of linitis plastica of the rectum treated by pelvic exenteration after aggressive immunochemotherapy , Springer Japan, Volume 22, Number 2, March 1992, p 159:162 4. Park W J, Christopher C. Benz, 24th Nov, 2007, Immunotherapy Cancer Treatment, Viewed on 9th September, 2008, http://www.cancersupportivecare.com/immunotherapy.html 5. Elkord E, 21st November 2007, From Prostate Cancer and Prostatic Diseases, Immunology and Immunotherapy Approaches for Prostate Cancer, Prostate Cancer Prostatic Dis.  2007; 10(3):224-236.  ©2007 Nature Publishing Group 6. Riker† I A, Radfar S, SuHu Liu, Wang Y & T Khong T H, 2007, Immunotherapy of melanoma: a critical review of current concepts and future strategies, Expert Opin. Biol. Ther. (2007) 7(3) http://www.usamci.com/spf90/riker2.pdf 7. Kim J C, Dessureault S, Gabrilovich D, Reintgen S D, Slingluff L C, Immunotherapy for Melanoma, Cancer Control 9(1):22-30, 2002. © 2002 H. Lee Moffitt Cancer Center and Research Institute, Inc 8. Amor Khachemoune; Eric Ehrsam posted on 19th July, 2005, Assessing Malignant Melanoma: A Case Study, Dermatol Nurs.  2005; 17(3):188-190. 9. Hoffmann K, Marten A, Lindel K, Fritz S, Jager D, Buchler W M , Schmidt J, 17th Nov, 2005, Major combined electrolyte deficiency during therapy with low-dose Cisplatin, 5-Fluorouracil and Interferon alpha: report on several cases and review of the literature , BMC Cancer 2006, 6:128doi:10.1186/1471-2407-6-128 10. Spontaneous Regression of Cancer: Summary and Profile for the Future, National Cancer Institute Monographs 44: 1976; 145-148, NOSSAL GJV, Extracted Summary Read More