The Current Landscape of Immunotherapy in Cancer Treatment
Introduction to Immunotherapy
Cancer and Immunotherapy: Cancer is a much more heterogeneous disease than was originally believed, with substantial differences in clinical behaviour, response to therapy, and prognosis, even among tumours that, from a microscopic point of view, look very similar. Over time, this realisation led to the identification of many molecular alterations underlying these differences, but primarily to the reorganisation of cancer diagnosis and treatment strategies. The development of new technologies and molecular concepts allowed researchers to develop a diverse catalogue of drugs able to target specific tumour dependencies. These drugs can be broadly classified into two main groups: targeted agents, able to recognise the transforming core of cancer, and antitumoural immune drugs, serving to reactivate and unleash a previously inhibited antitumoural immune response.
Immunotherapy has always been, somewhat modestly and unconsciously, a part of oncological knowledge. Patients presenting with tumours that impair and suppress the immune system have worse prognoses than those presenting with tumours easily recognised by lymphocytes that destroy them or by other viable immune reactions. This, in fact, formed the base of the rationale underlying the development of a large part of the current pharmacological arsenal of antitumoural therapies. In the comprehension, development, and use of such drugs, the focus shifted from the tumour to the host, increasing interest not only in the biology but also in the distinct aspects of the host-tumour relationship. Until quite recently, it was believed that it was enough to identify and control the molecular pathways moving through the cancer cells and their microenvironment to control cancer. But it is now widely accepted that effective antitumoural therapy should include tumour-inhibited immune reactivation, that diverse forms of immunotherapy can mediate such reactivation. This hypothesis found initial scientific backing from the observation of tumour regression following host immune system stimulation to fight off infections or to reject allogeneic transplant organs. More direct evidence of cancer immunosurveillance as a vital process evolved from studies demonstrating an increased incidence of spontaneous tumours in immunocompromised host model strains.
Definition and Principles
Immunotherapy refers to the treatment that uses certain parts of a person’s immune system to fight diseases such as infections or cancer. Cancer immunotherapy is the use of the immune system to treat cancer. The goal is to prevent cancer cells from escaping the immune system and entice the immune system to recognize and destroy cancer cells. As an exciting innovation in cancer treatment, immunotherapy restores and enhances the immune system’s ability to recognize and destroy cancer cells. The fact that cancer cells arise from the patient’s tissues makes them more likely to be recognized by the immune system. Many clinical trials have shown that immunotherapy is effective against multiple cancer types given the legendary mechanism, the associated immune-related adverse events, as well as the long-term survival witnessed in only a small subset of patients.
Types of Immunotherapy
By activating an individual’s immune cells or administering exogenous activated immune cells, or immunotherapeutic tumor antigens, cellular and cytokine immune responses can be boosted or rebuilt to enforce anti-tumor effect. Thus, there are many different forms of immunotherapy which are exploited for the treatment of cancer. Currently, different types of immunotherapy strategies have been shown to be ideal cancer treatment methods. Tumor eradication can be achieved via various adoptive cell transfer strategies, which contain tumor-infiltrating lymphocytes, chimeric antigen receptor T cells, donor lymphocyte infusion, natural killer cell therapy, γδT cell therapy, cytokine induce killer cell immunotherapy, and ex vivo primed vaccine, and so on. On the other hand, many critically essential cytokines, such as interleukin 2, interleukin 7, interleukin 15, and interleukin 21, can act as effective tumor treatment agents.
In addition to cellular immunotherapeutic agents, various tumor antigens might be ideal agents for anticancer vaccination, especially when they are used in combination. These tumor antigens can either be tumor-associated antigens in patients’ bodies or the mutated neoantigens which arise during tumor development. Tumor antigens can boost cancer treatment by activating tumor-killing T cell responses. Recently, DNA vaccines were developed which have been applied in tumor therapy. Currently, the oncolytic virus has been presented as a new tumor antigens agent, which can release the tumor-specific antigens following its destruction of the infected cancer cells. Small interfering RNA or microRNA molecules might act as novel cancer immunotherapeutic agents by inhibition of gene expression too. Finally, incorporation of adjuvants into a therapeutic vaccine can enhance the magnitude and quality of therapeutic vaccine-induced immune responses.
Checkpoint Inhibitors
Although the majority of cancer types have mechanisms to express ligands that negatively regulate CTL function, the concomitant expression of the negative PD-1 receptor on CTL during the course of chronic antigen exposure indicates that this adaptive strategy is important in preventing autoimmunity during normal immune responses to self-constituents or persistent/latent infections. While these regulatory ligands are undoubtedly effective in dampening CTL effector function, their mode of action is distinct from the interactions of coinhibitory receptors such as CTLA-4 that inhibit the early initiation of the immune response by blocking the costimulatory pathways involved in T-cell priming. This difference in the role of ligands that prevent initial activation versus those that interrupt an immune response that is still in progress is likely to affect the expression pathways of the respective molecules.
In addition, the relative abundance of PD-1 in noncancer-specific CTL that infiltrate the tumoral microenvironment distinguishes it from immunotherapies targeting antigens, costimulatory factors, or the signaling pathways responsible for activation in tumor-specific CTL. These agents have the potential to induce pathologic autoimmunity involving large numbers of noncancer-specific CTL, whereas PD-1 blockade acts to alleviate an antigen-specific immunosuppressive mechanism at a tumor site. As a result, the potentially deadly autoimmunity experienced in a minority of human subjects treated with costimulatory-targeted CTLA-4 therapy was believed to be largely averted by the PD-1 abrogation of tumor-mediated immunosuppression, leading to the explosion of PD-1 targeting as one of the more effective and widely applied immunotherapy strategies in the past decade.
Monoclonal Antibodies
Monoclonal antibodies (mAbs) are laboratory-generated proteins or immunoglobulin (Ig) moieties designed to target specific antigens, including those expressed by human cells. Detection, binding, and recognition of the foreign molecule result in triggering immune responses to maintain homeostasis. The whole antibodies are complex glycoproteins composed of two heavy and light chains held together by disulfide linkages. The hinge region separates the higher fragment (Fab), which recognizes and binds the specific antigens, from the lower fragment (Fc), which mediates biological effector functions such as binding proteins of the immune system, including the following: i) C1q fixation for complement activation II; ii) recognition of Fc receptors (FcRs) that promote most of the clinical uses of mAbs, viz., antibody-dependent cellular cytotoxicity (ADCC), phagocytosis by macrophages, and the release of cytokines and other inflammatory mediators, which are best when proportional to the numbers and type of FcRs interacting with the mAbs. Substantial Fc-FcR engagements create sizable antitumor activity of mAbs.
Challenges and Future Directions
Although immunotherapy has some positive aspects, it also has challenges that need to be addressed. Failure in the treatment of a substantial number of patients, the high cost of development of personalized and combinatorial therapies, and the side effects of immune responses are among them. Some of the patients do not respond to immunotherapy, and drug resistance occurs in some of the patients who initially respond. To overcome these problems, the first thing to be done is in-depth research of the employed or newly developed agents. In this way, the patients who could benefit from the potential therapy and possible causes of drug resistance can be detected by combining clinically relevant data and complementary laboratory experiments.
Read about Advances in the Treatment of Neurological Diseases
https://www.ihmorg.org/advances-in-the-treatment-of-neurological-diseases/
Conclusion
Immunotherapy represents a promising frontier in medicine, harnessing the body’s own immune system to combat diseases more effectively. As research advances, it holds the potential to revolutionize treatment approaches and improve patient outcomes across a range of conditions.
INTERNATIONAL HEALTH AND MEDICINE ORGANIZATION IHMO
