Modifiers of TGF-beta1 effector function as novel therapeutic targets of pulmonary fibrosis

Pulmonary fibrosis is a fatal progressive disease with no effective therapy. Transforming growth factor (TGF)-beta1 has long been regarded as a central mediator of tissue fibrosis that involves multiple organs including skin, liver, kidney, and lung. Thus, TGF-beta1 and its signaling pathways have been attractive therapeutic targets for the development of antifibrotic drugs. However, the essential biological functions of TGF-beta1 in maintaining normal immune and cellular homeostasis significantly limit the effectiveness of TGF-beta1-directed therapeutic approaches. Thus, targeting downstream mediators or signaling molecules of TGF-beta1 could be an alternative approach that selectively inhibits TGF-beta1-stimulated fibrotic tissue response while preserving major physiological function of TGF-beta1. Recent studies from our laboratory revealed that TGF-beta1 crosstalk with epidermal growth factor receptor (EGFR) signaling by induction of amphiregulin, a ligand of EGFR, plays a critical role in the development or progression of pulmonary fibrosis. In addition, chitotriosidase, a true chitinase in humans, has been identified to have modulating capacity of TGF-beta1 signaling as a new biomarker and therapeutic target of scleroderma-associated pulmonary fibrosis. These newly identified modifiers of TGF-beta1 effector function significantly enhance the effectiveness and flexibility in targeting pulmonary fibrosis in which TGF-beta1 plays a significant role.

Biologic response modifiers

Biotherapy, often called biological therapy or immunotherapy, aims at supporting and helping in the treatment of human disease without chemical drugs and invasive therapies, by restoring the natural immune system. It is also used to reduce certain side effects that may be caused by some treatments against cancer, autoimmune diseases, or other diseases. Biotherapy employs substances called biological response modifiers (BRMs). The term BRM is often used synonymously with the terms immunomodulator and immunostimulant. BRMs are agents that modify the host's response to pathogens with resultant beneficial prophylactic or therapeutic effects. The use of BRMs had rapidly expanded since the introduction of the first diagnostic antibodies. They are now employed in oncology, autoimmune diseases, inflammatory diseases, and transplantation medicine. BRMs used in biological therapy include interferones, interleukins, colony-stimulating factors, monoclonal antibodies, differentiation agents, tyrosine kinase inhibitor, tumor necrosis factor, vaccines, and nonspecific immunomodulating agents. BRMs are widely accepted in the treatment of certain types of cancer and rheumatoid arthritis, while others are being tested in research studies. This article reviewed the clinical use and side effects of BRMs in cancer and other diseases.

Biological response modifiers: Current use and future prospects in cancer therapy.

Over the past few decades, considerable success has been achieved in the field of cancer treatment with biological response modifiers (BRM), which are agents that improve the body's ability to fight cancer by immunostimulation. Biological agents, such as interferons and interleukins, provide nonspecific active immunity, whereas the monoclonal antibodies provide passive immunity. Apart from this, other biological agents, such as antiangiogenic agents, matrix metalloprotease inhibitors, tyrosine kinase inhibitors, and tumor vaccines, are also increasingly being used in cancer treatment. Hematopoietic factors, such as granulocyte colony-stimulating factor, are used to increase the general immunity and prevent opportunistic infection. BRM are basically used alone or as adjuvants to cancer chemotherapeutic agents. This review sheds light on the current use and the future development of cancer immunotherapy. Search strategy included Pubmed, using the terms "Biological response modifiers in cancer" citations relevant to the topic were screened.