Antibodies can act as a ‘magic bullet.’ Therefore, antibody–drug conjugates (ADCs) and T cell–dependent bispecific antibodies (TDBs) enable specific delivery of drugs and T cells, respectively, to tumor cells. Moreover, immune targeting represents a new concept in drug delivery systems (DDSs); for example, a lymphocyte-targeting antibody can effectively treat inflammatory autoimmune diseases and cancers. Furthermore, therapeutic antibodies have been used in clinics to treat several refractory and therapy-resistant infectious diseases. However, this approach has some disadvantages, including antibody-dependent enhancement (ADE), interstitial pneumonia, and cytokine storm. These issues may be associated with severe cases of COVID-19 infection. Here, I will review recently developed antibody DDS therapeutics and a vision for it across the fields of cancer, inflammatory autoimmune disease, and infectious disease.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and the use of some disease-modifying drugs (DMDs) to control the neurodegenerative symptoms and to reduce the relapse rate has become the mainstream approach for clinical treatment of MS. Herein, I review the clinically-used DMDs in Japan and recent studies for the development of DDS drugs to treat MS. Then, I explain a targeting DDS with immune antigen-modified liposome for the treatment of immune diseases and finally introduce my recent research on the development of autoantigen-modified liposomal drug for the treatment of MS.
The treatment of autoimmune diseases has advanced dramatically with the use of biologics, in recent years. JAK inhibitors have shown groundbreaking efficacy as oral medications and several drugs have been approved. The efficacy of these drugs is not limited to rheumatoid arthritis, but they are also effective in treating auto-inflammatory diseases such as inflammatory bowel disease. However, sufficient efficacy has not been observed in treating autoimmune diseases.
In the 1980s, the average life expectancy following an AIDS diagnosis was approximately one year. Today, with combination antiretroviral therapy (cART) started early in the course of HIV infection, people living with HIV can expect a near-normal lifespan. The success of cART, combined with powerful but nonetheless less toxic drugs has transformed HIV/AIDS from an inevitably fatal disease into a manageable chronic infection. The history of the human immunodeficiency virus (HIV)/AIDS therapy, which spans over 30 years, is one of the most dramatic stories of science and medicine leading to the treatment of a disease. In this review article, I would like to try to describe about the history of developing anti-HIV drugs with my personal experiences.
While it is difficult to secure the abundant systemic exposure of CYP3A/P-gp substrate drugs such as HIV protease inhibitors, pharmacokinetic booster contributes to the drastic improvement of their systemic exposure by potent inhibition of their metabolic and efflux pathways. Traditionally, low dose of ritonavir (compared with therapeutic dose for HIV treatment) has been used. Recently, cobicistat, a structurally-related compound of ritonavir without any pharmacological effect and induction potency of metabolic enzymes, has been created as a pure booster and is clinically used with other drugs as a combination drug. Both ritonavir and cobicistat potently inhibit intestinal and hepatic CYP3A, whereas only ritonavir also leads to the induction of multiple metabolic enzymes. Thus, in the case of the change of prescription between ritonavir and cobicistat, we must pay attention to the significant alteration in the pharmacokinetics of co-administered drugs.
Almost 40 years after the discovery of HIV-1/AIDS, combination anti-retroviral therapy (cART) has dramatically improved the prognosis of people living with HIV (PLWH), and AIDS has become a treatable chronic infection from a fatal disease. Recently, new effective and safe anti-HIV drugs have been developed one after another, and UNAIDS aims to end the AIDS epidemic by 2030. On the other hand, although cART can reduce the viral production in the PLWH’s body below the detection limit, it can not eliminate the HIV provirus integrated into the gene in the host cells. Therefore, the virus will be produced again after discontinuation of the drug. Under such circumstances, research for the cure (or remission) of HIV has been widely carried out. In this review, we focus on the drug development targeting HIV latently infected cells and overview the progress including our current studies.