Immunotherapy for cancer treatment has had tremendous growth recently with increased awareness and knowledge of the immune system and potential means to manipulate it for therapeutic intent. Progress in the treatment of viral infections including CMV, EBV, HHV-6, utilization of immune checkpoint blockade for melanoma, non-small cell lung cancer, and Hodgkin Lymphoma, as well as rapid emergence of genetically modified T cells against CD19+ B cells have contributed to the growth in this area.Antibody-targeted therapy has now become standard of care for many malignancies, and the multi-domain utilization of antigen-specific adoptive T-cell therapy has shown great promises. 4 While our understanding of B cell and T cell and our ability to …show more content…
The key role of NK cells in various aspects of immune response are now being recognized and have been attracting increased attention for their potential clinical efficacy via immune-based therapies. As their name implies, this unique member of the innate immune system can recognize targets without being previously sensitized and thus kill cells that are deemed dangerous to the host. This is particularly important when evaluating biologic studies of NK cells and factors that influence NK-cell effect in cancer immune-surveillance, viral immunity, and transplantation alloreactivity. In this chapter, we will review NK cell biology, discuss their role in the alloHSCT setting, and review new advances in incorporating NK cells as therapeutic options for malignancies. Large granular lymphocytes (LGL) can be divided broadly into two major lineages mainly T cells and natural killer (NK) cells. While mature cells NK cells are morphologically identified as LGL, nearly a decade after their initial discovery, NK cells were characterized as lymphocytes having an immuno-phenotype that lacked expression of CD3- but expressed CD56+. This characterization thereby differentiated them from T-cells having CD3+ expression and thus NK cells do not express the CD3/T-cell receptor (TCR) complex or experience TCR gene rearrangement. NK cells can be further divided into two distinct
A key factor in the development of tumors is the ability of cancerous cells to evade recognition from the bodies’ natural defense against cancer, the immune system. Immunotherapies effectively block the pathways that shield cancerous cells from being identified, and thus the promote the bodies own anti-tumor response. However, one challenge to immunotherapy has been its combination with chemotherapy, the mainstay of cancer treatment. While chemotherapy is extremely effective in stopping the rapid division of cancerous cells, its toxic immunosuppressive side-effect make it difficult to combine with
In this issue of Lancet Oncology, Dr. Antonia and colleagues report on the combination of durvalumab and tremelimumab in patients with non-small cell lung cancer (NSCLC).1 After the recent approvals of nivolumab and pembrolizumab in NSCLC,2, 3, 4 there is a near frenzy of attempts to combine agents with inhibitors of the PD-1 immune checkpoint. Some efforts are based on only the shakiest of scientific evidence. However, the combination of durvalumab, a PD-L1 inhibitor, and tremelimumab, a CTLA-4 inhibitor, has a sound scientific basis. Dual checkpoint inhibition is now an established treatment option for patients with advanced melanoma.5, 6
Some of traditional drugs may be effective in patients whose cancers have a specific molecular target, and not for other patients. To solve this problem of patient-specificity, pharmaceutical research have seen the expansion of individually tailored cancer treatment, which is an application of targeted therapy, and this is where biopharmaceuticals are. As an increasing part of the population is diagnosed with cancer and as these patients live longer, increasing care will be given to patients who have received these drugs. Moreover, in the case of cancer therapy, those drugs and especially with mABs are a promise of less side effects : recombinant DNA technology makes it possible to genetically engineer an antibody to reduce the risk of host immune response.
Many doctors, physicians, researchers and biotech companies--including the revolutionary Seattle Genetics research facility--are now turning to antibody-assisted cancer treatments and precisely targeted cures instead of treating cancer with a cocktail of chemicals and radiation that generate risky side effects and damage the healthy tissue that patients need to recover. Cancers are among the most frightening and difficult-to-treat illnesses. Ranked as the leading cause of death and disability, cancer is actually an umbrella term that covers many different diseases. Each person faces a unique disease because cancers interact with the body's existing cells, so each case has a
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
Thank you for the informative post. I liked how you compared the costs of chemotherapy treatment for breast cancer versus mammography. Looking at chemotherapy treatment, from an economic point of view. The treatment is costly and is controversial regarding the efficacy of the treatment. The patient's use of chemotherapeutic agents has led to longer treatment times; which resulted in small incremental gains in survival at considerable additional costs (Haywood et al., 2012). Moreover, healthcare decision makers are in a precarious situation. There is great tension between providing the patient, with the best available treatment options. To improve patient outcomes and the budgetary and resource impact of funding the treatments (Haywood et al.,
In the bloodstream, a very small number of tumor cells survive to reach the target organ, indicating that metastasis formation must be regarded as a very ineffective event [7,8]. Millions of carcinoma cells enter into the circulatory system, but the majority of them die during transportation, and only 1-5% of viable cells are successful in formation of secondary deposits in distinct sites [7-9]. It is known that many cells of the immune system, such as NK cells, macrophages and lymphocytes, could contribute to the elimination of tumor cells in the vascular
Lymphoma is a cancer that starts in our cells and affects our immune system (“Lymphoma”). The natural killer cells in our bodies, also known as NK cells, can fight off the malignant lymphoma cells for our immune system. They are an important part of our immune system because they allow immunity of dangerous and altered structures. The only problem is, they lose their effect once they are within the vicinity of the tumor itself. With belief that natural killer cells are very therapeutic to killing lymphoma cells, scientists of Helmholtz Zentrum Munchen have discovered a way to fix this.
A 45 year old male, with a history of smoking ½ packs of cigarettes a day for the past 30 years has been diagnosed with laryngeal cancer. The patient comes into the hospital for a follow up visit to his health care provider. Where he has been getting radiation and chemotherapy treatments for the cancer. He has complaints of pain, dyspnea at times and dysphasia. While discussing the progress of his condition the doctor states that the chemo and radiation therapy has not been successful and the cancer has started to progress. The doctor then states the next steps to prevent the spread of the cancer, and that’s to have total laryngectomy surgery. The patient understands the severity of his condition but is now experiencing anxiety because of
The genetic engineering T cell therapy in oncology are characterized by influx of investment, rapidly advancing technologies and intense competition. Our competitors include leading multinational pharmaceutical companies, established & newly founded biotechnology companies and potentially universities and research institutions. We compete with companies in the space of immunotherapy as well as companies developing novel targeted therapies for cancer. We will cover China market and thus competing with local biotechnology and pharmaceutical companies in China. We are facing intense and likely increasing competitions with current approved drugs and potentially new drugs and therapies entering the market. Our competitors may be able to develop other compounds or drugs that are able to achieve similar or better results.
Patients with primary immunodeficiency (PID) are at an increased risk of malignancy compared with the normal population [1-4]. After infections, malignancy is the second most common cause of death in these patients [1]. According to the Immunodeficiency Cancer Registry (ICR) database on immunodeficiency-associated cancer at the University of Minnesota, the most common types of malignancies among PID patients are NHL, which account for 48.6 percent of cancers seen in PID patients. (UPTODATE). NHL is frequently caused by infection with the ubiquitous EBV. The infection of B-cells by EBV provokes a marked activation of immunoregulatory T-cells and requires restoration of immune homeostasis during convalescence. This is accomplished with difficulty in an individual with significant immune defects. (PAAM). It is not surprising, therefore, that immunodeficient individuals are at great risk of developing immunoregulatory disturbances and lymphoproliferative diseases when confronted by EBV. Patients,
As the world continues to suffer from these devastating diseases, researchers continue to find alternative therapeutic ways of addressing cancer treatment. It is on this premise that various immunotherapeutic alternatives have emerged and currently garnering the greatest level of attention and already raising hope throughout the world in addressing the treatment of NSCLC. However, this can no longer be viewed as a discovery but a wave in the medicine world that began in the 20th century. Various researchers have found the importance of the role of immune systems in fighting the growth of tumor caused by cancer cells. A study by Huncharek (2000) stated that specific immune boosters are capable of eliminating preclinical cancers. In contrast, Jermal et al. (2011) found that immunotherapy is an effective approach for the treatment of tumors that have already turned into solid. Similarly, the researchers highlighted that immunotherapy can be an effective approach to the treatment of melanoma as well as renal cell cancers (Lasalvia-Prisco, 2008). However, Jemal et al. (2011) noted that immunotherapy cannot achieve much in cancer treatment due to limitation brought about by the emission of immunosuppressive cytokines and subsequent loss of antigen expressions. Recent development in research studies on the immunotherapy approach to cancer treatment continues to elicit mixed reactions among researchers of medicinal ecology (Jadad et al., 1996). However, recent development in
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.
Cancer immunoediting involves three major phases; 1) Elimination 2) Equilibrium and 3) Escape (Dunn et al., 2002). In the early elimination phase, tumors are immunogenic and are susceptible to host adaptive immune response. The coordinated innate and adaptive response is in part due to tumor intrinsic genomic instability and other hallmarks of the tumor (Dunn et al., 2002). In this phase, the tumors also express tumor-specific/associated antigens, or tumor- specific neoepitopes that are derived from the antigen presentation of non-synonymous mutations on HLA class I molecules. Tumors in this phase can also be susceptible to CD4+ T-cells if theyare antigenically processed and presented by APCs, NK cells if they lack antigen presentation, and other various different types of immune-mediated cell death (Dunn et al., 2002). Thus, the elimination phase is a direct consequence of the immune
Despite the addition of CKB antibodies in the ex vivo T-cell stimulation protocol, we detected low levels of E7-CTLs compared to E2 and E6-CTLs in this study. This can be due to 1) inaccurate prediction of CTL-epitopes, 2) inherently low immunogenicity of E7-antigen, 3) low antigen load in patients, or 4) higher levels of dysfunctional E7-specific CTLs. Our ability to accurately predict previously described epitopes from E7 and the successful identification of novel CTL-epitopes from E2 and E6 across various HLA-alleles (Fig. 4-3), argues against a sub-optimal prediction strategy. The presence of high levels of serum titers against E7 in HPV+ HNSCC patients indicates that the antigen is