Introduction
Scientists believe that the industrial revolution is the main factor that led to the rise in tooth decay and gum diseases among the people. Tooth decay and gum diseases are believed to have increased as a result of heightened consumption of starch and sugary foodstuffs. Increased invention in agriculture and industrial products led to dietary changes (Ivanyi 2012), which negatively affected the balance of oral bacteria. Revolution in farming led to increased production and consumption of wheat and barley, which are believed to have completely changed the oral ecosystem. A change in the oral ecosystem led to a drastic reduction in oral bacteria diversity (Ivanyi 2012). Harmful bacteria whose population is kept minimal by beneficial bacteria increased significantly in the oral cavity leading to a myriad of devastating oral health conditions. It is presumed that human ancestors had healthier oral cavities than that of the modern human beings.
Numerous studies have been carried out on the subject of oral diseases to determine their actual causes as well as the most practical ways through which these conditions can be managed and prevented. Studies have also been conducted to determine the types of bacteria that inhabit the oral cavity, their benefits as well as their potential harm (Osbourn, Jermutus & Duncan 2003). These studies are targeted towards determining the most appropriate ways through which beneficial bacteria can be boosted in order to suppress disease-causing bacteria and other microorganisms (Daugherty & Mrsny 2006). In order to relieve human beings of the burden of oral diseases, scientists have devised different treatment, management and prevention tactics. One of these strategies that have raised heated debates over the recent times is the use of monoclonal antibodies and the application in dentistry. This paper through qualitative analysis of legitimate websites sources and peer review journal articles is going to address some of the issues associated with the use of Monoclonal antibodies in dentistry. The benefits, potential disadvantages and the hindrances of the use of this medical innovation shall be looked at in this paper.
Monoclonal antibodies and the application in dentistry
Advancement in medical science over the last twenty years has recorded tremendous steps in immunology. The demonstration of monoclonal antibodies forms part of the significant millstones in humoral immunity. Molecular immunology is among the most recent scientific advancement that is predicted to hold the promise of solving some of the greatest dilemmas in immunology. Major benefits of molecular immunology have already been witnessed in diagnostic medicine. These benefits are mainly associated with specificity and sensitivity of antibodies (Ma, Hunjan, Smith & Lehner 1989). Oral and dental diseases have not been exempted from the benefits of molecular immunology. Immunology is believed to have increased the molecular knowledge of the two most common dental diseases, the dental caries and periodontal diseases as well as recurrent oral ulceration among other conditions (Osbourn, Jermutus & Duncan 2003).
Researchers have realized that most conventional treatment modalities do not have the capacity to manage some health conditions, which have turned out to be a huge burden to human beings (Sfikakis 2002). This realization has led to increased investment in scientific research in an attempt to develop competent treatment modalities that can address the root causes of major diseases (Liu 2014). The use of monoclonal antibodies is among the modern treatment modalities that scientists believe hold the promise of tackling a large proportion of devastating health conditions. Monoclonal antibodies are used for local passive immunization against mutants that result in devastating health conditions. This form of immunization is largely used as an alternative approach to systemic immunization (Lehner, Caldwell & Smith 1985). Microorganisms within the oral cavity cause periodontal diseases and dental carries. Research has not identified the definite mechanisms of pathogenesis of various virulence factors of oral microorganisms (Abiko 2000). The complex nature of the bacterial community in certain oral conditions, including dental plaque, makes it difficult for identification of single bacteria agent responsible for these conditions. This have in the past produced devastating results whereby the oral ecosystem is damaged in an attempt to eradicate certain pathogenic bacteria. Some treatment strategies are believed to erode even the beneficial bacteria agents (Ivanyi 2012).
Researchers point out that Streptococcus mutans are the main causative agents of oral diseases, especially dental carries (Abiko 2000). Specific subgingival bacteria are also believed to cause certain oral conditions. For instance, Porphyromonas gingivalis has been associated with adult periodontitis. The disease process of these conditions starts with the adherence of bacteria to host tissues, an aspect that results in colonization. Colonization of bacteria is facilitated by hemaglutinins and bacterial coaggregation factors (Abiko 2000). Evidence from recent studies reveals that if these virulence factors were inhibited, the oral cavity would be protected from periodontal disease (Ivanyi 2012). Inhibition of these factors is usually done through active and passive immunity. Advancement in mucosal immunology as well as development of new strategies to induce mucosal immune responses support the possibility that highly efficient and safe vaccines can be developed (Ivanyi 2012). Considering that the public might be skeptical on the critical nature of dental diseases, immunotherapy should be conducted with extreme caution (Abiko 2000). This goal can only be achieved through the development of safe antibodies for passive and local immunity. Antibodies can be used in the management of dental diseases since they have extraordinary specificity of target identification and therefore produce highly selective results after a systematic administration (Ma, Hunjan, Smith & Lehner 1989).
One of the major disadvantages associated with the use of antibodies in the management and prevention of major health conditions, as noted by Liu (2014), is that large doses are required to achieve the expected results. This calls for advancements in production and purification capacities in order to produce large quantities of highly purified monoclonal antibodies. Genetic engineering of antibodies is one of the strategies used to produce stable antibody-like proteins (Flego et al. 2013). This has led to increased consideration of the application of monoclonal antibodies in dentistry.
Monoclonal antibodies can simply be described as copies of a particular type of antibody that are produced in the lab. The main mechanism of action of antibodies is through recognition and attaching to specific proteins produced by certain cells. A particular monoclonal antibody recognizes and attaches to only a specific protein (Liu 2014). In order for monoclonal antibodies to perform their role effectively in the treatment of dental conditions, they have to be made to target the actual causes of diseases (Ivanyi 2012). It is also important to understand the possible side effects that might emanate from the use of monoclonal antibodies. The mode of action differs in accordance with the type of protein the antibody targets and attaches. Monoclonal antibodies may act through triggering the immune system to attack cancer cells, carrying drug molecules to the affected cells, or through blocking intracellular communications that result in multiplication of disease causing microorganisms (Weiner Surana & Wang 2010).
Key technological developments of mAbs
The development of monoclonal antibodies as therapeutics has increased significantly over the last four decades. Fully human monoclonal antibodies have become a growing category of therapeutic agents targeted by scientists for the management of major health conditions, including dental conditions and cancer (Weiner Surana & Wang 2010). The first batch of fully human monoclonal antibodies was developed in the 1980s. However, it was not utilized for clinical or commercial purposes because of issues associated with purity and safety of the substance. Technological advancement to generate monoclonal antibodies for research purposes revived the interest to develop fully human monoclonal antibodies in the 1990s. The U.S Food and Drug Administration developed the first human mAbs, adalimumab in 2002. Since then, more fully human mAbs have been developed (Liu 2014).
Human monoclonal antibodies are believed to be the fastest growing category of monoclonal antibodies that are being used in clinical studies. Despite the fact that the technologies developed in the 1970s through 1980s can still be applied for production of human mAbs, manufacturing challenges limit the use of old technology in the manufacture of mAbs (Liu 2014). Over the years, scientists have relied on the production of murine antibodies since they are easier to produce as compared to human mAbs. However, issues associated with safety and minimal efficacy limit the use of murine antibodies. This challenge is attributed to immunogenicity of mouse-derived protein sequences (Yeh et al. 2006).
The last three decades have seen an increase in scientific exploration to enhance the characteristics of therapeutic monoclonal antibodies. This exploration is based on the perception that a reduction of the murine-derived sequences would eliminate mAb immunogenicity (Ivanyi 2012). This led to the division of mAb studies with one path leading to development of fully human mAbs and the other one leading to the development of rodent derived mAbs. Most of the studies on monoclonal antibodies conducted from the 1990s adopt either of the two paths. More than two thirds of mAbs in the U.S market currently are either humanized or chimeric products (Liu 2014). At the early stages of the monoclonal antibody technology, human mAbs could only be generated through a few methods, which include human hybridomas, as well as immortalization of primary human lymphocytes (Modjtahedi, Ali & Essapen 2012). Despite the fact that these approaches were highly innovative, they could not be utilized clinically due to the unreliable nature of the mAbs. Research for the clinical use of monoclonal antibodies in the management of immunological disorders was initiated in 1996 (Ivanyi 2012). Researchers started focusing on how mAbs could be used in the treatment of severe health conditions. Studies were later on broadened to include disorders emanating form, viral and bacterial infections including oral diseases (Ma et al. 1998).
Active immunization tactics have been developed to protect human beings against periodontal disease and dental caries. Reports have demonstrated the efficiency and the promise of active immunization in experimental animal models (Modjtahedi, Ali & Essapen 2012). This has led to an increase in the number of studies conducted to determine whether monoclonal antibodies can be used in local passive immunization to reduce cases of colonization of human oral cavity by streptococcus mutans. Most of these studies are conducted on monkeys, and have revealed that mAbs protect monkeys from streptococcal mutans’ colonization of the dental cavity. Streptococcus mutans are the causative agents of dental carries. In a particular study, as described by Ma, Smith, and Lehner (1987), the researchers used eight healthy subjects where four of them had a streptomycin-resistant S. mutans strain introduced into their dental cavity. The organism was cultured regularly for three months from the dental plaque of the four subjects following treatment with mAbs. The researchers found out that there was a decrease in colonization by streptococcal mutans in the dental plaque collected from the subjects who had been administered with mAbs. Subjects who were treated with saline had a high level of colonization by S mutans. The researchers repeated this experiment on other subjects using Campylobacter jejuni (Ma, Smith, and Lehner 1987). The results were positive and there was a significantly reduced rate of C jejuni colonization of subjects who were treated with mAbs. The results however indicated that colonization was high in subjects who had been treated with an unrelated mAbs. At this early stage of mAb development, Ma, Smith and Lehner (1987), pointed that mAbs might be applied as alternative treatment strategies to prevent colonization of the dental cavity by S mutans hence decreasing the development of dental caries.
It is important to note that current perceptions of the cause of periodontal diseases and dental caries focus on the association between the susceptibility of hosts and the suspected pathogens (Modjtahedi, Ali & Essapen 2012). Scientists and health care givers also believe that periodontal diseases have a significant impact on the occurrence of certain potentially fatal health conditions including bacterial pneumonia, cardiovascular diseases and diabetes mellitus (Yeh et al. 2006). These factors have led to a limited application of mAbs in the prevention of dental diseases since it is not clear how different people might react to these therapeutic substances (Shefet-Carasso & Benhar 2015). Nevertheless, a direct association between periodontal disease and the secondary health conditions has not yet been confirmed. Scientists hope that efficient control of putative pathogenic microorganisms will turn out to be an important objective in dental science in the future.
Local passive immunization is the best way to administer mAbs in the management of dental diseases. This process comprises an injection of antiserum into the dental region. However, side effects may occur due to the use of foreign (non-human) serum (Ma et al. 1998). Fortunately, in reference to periodontal diseases and dental carries, because the basic pathological sites are the gingival tissue and the surface of the teeth, it is likely that antibody injection may not be necessary (Ma et al. 1998). Effective immunization against these dental conditions can be achieved through a simple mouthwash with a specific antibody- specific to the area and the bacteria agent being targeted (Ma et al. 1998). Despite the fact that passive immunization of the oral cavity tissues is perceived to be safe, it is important to develop safe neutralizing antibodies for efficient results.
MAbs can be used in the treatment of oral cancer, especially cancerous conditions associated with the gum. The major growth factor that has been attributed to the proliferation as well as survival of cancerous cells in the gum is the epidermal growth factor receptor (EGFR) (Bianco et al. 2005). Monoclonal antibodies against cancer target the EGFR (Cohen 2014). In cancer treatment, the inhibition of EGFR functions is done through small-molecule tyrosine kinase inhibition as well as through administration of neutralizing monoclonal antibodies. Antibodies against epidermal growth factor receptor 1 (EGFr-1) are used as treatments for head and neck cancer that express higher levels of this marker on the surface (Cohen 2014); and antibodies against CD20 to deplete B-cells in Pemphigus vulgaris, leading to the complete remission of this autoimmune disease.
Scientists believe that antibodies are major components of the adaptive immune response. These immune components play a central role not only in the recognition of potentially pathogenic organisms, but also in the stimulation of immune response (Feldman 2015). mAbs are also believed to be highly effective in the clearance of infected cells as well as viruses (Flego et al. 2013). Monoclonal antibodies offer protective effects through viral neutralization. This is the process whereby antibodies disrupt the interaction between ligands and microbic antigens. This activity provides natural protection as well as protection following immunization. SjÃgren’s syndrome is among the other oral conditions that can be managed with mAbs. This disease can adversely affect the condition of the mouth if left untreated. SjÃgren’s syndrome is an autoimmune disorder that affects the immune cells of the exocrine glands within the oral and the ocular cavities. Some of the symptoms of this disease include wobbling of the teeth, and painful gums. In extreme cases, the teeth may break and fall off (Sjogren’s Syndrome Foundation 2004).
Conclusion
It can be concluded that monoclonal antibodies hold the promise of tackling a wide range of dental conditions that have become a huge burden to the people. Immunology has increased the knowledge of the most common dental diseases, the dental caries and periodontal diseases. The use of monoclonal antibodies is among the modern treatment modalities that scientists believe have the potential to tackle a large proportion of devastating health conditions. Monoclonal antibodies are used for local passive immunization against mutants that result in devastating health conditions. Monoclonal antibodies can be used in local passive immunization to reduce cases of colonization of human oral cavity by streptococcus mutans, which cause dental caries. Considering that the public might be skeptical on the critical nature of dental diseases, immunotherapy should be conducted with extreme caution. This goal can be achieved through the development of safe antibodies for passive and local immunity.
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