Cytokines and growth factors

In the 1890s, William Coley (pictured) pioneered techniques that boost immune activity against cancer by injecting pathogens into cancer patients to stimulate their immune system. The modern emergence of onco-immunotherapy began with the therapeutic development of cytokines. These messenger proteins modulate both innate and adaptive immunity. Although they have been overshadowed by checkpoint inhibitors for the last decade, there is renewed interest in targeting and harnessing cytokines for cancer immunotherapy.

Mucosal surfaces are the primary interface between an individual and pathogens and are particularly vulnerable to infection. Yet, they also come into regular contact with a host of antigens that need to be tolerated. To allow tolerance and deal with a constant threat of infection, a dynamic and complex array of immune mechanisms provide a finely calibrated first response to these invasive microbial threats.

Cancer drug candidates sometimes emerge with exceptional promise but ultimately fall short. In the late 1990s, endostatin gained huge prominence and was widely viewed as an exceptional cancer drug candidate. But things didn’t quite work out. Although endostatin is now approved by the FDA, in the West it is largely forgotten, eclipsed by newer treatments. But look East, notably to China, and endostatin is very much at the forefront of cancer therapy, particularly in combination with chemotherapy. Why have its fortunes varied geographically and will it ever make a global impact?

Inflammation is critical for maintaining health, but, paradoxically, can also generate disease: Chronic inflammation is strongly associated with the development of cancer and is also a key driver of the ageing process. In addition, auto-immune diseases, of which there are very many, are debilitating and can lead to high rates of morbidity and mortality. Drugs that are able to specifically target the damaging aspects inflammatory responses whilst leaving critical functions intact can be hugely successful.

Why do some people fall seriously ill and die with Covid whilst others are asymptomatic? A remarkable characteristic of Covid-19 is the way it affects individuals so differently: Around 40% of people infected with SARS-CoV-2 are asymptomatic. A further 40% experience mild, upper respiratory tract symptoms. The remaining 20% develop pneumonia, of which 10% will become hypoxic, leading to critical illness in around 3%. In addition to age, sex and underlying health issues, the ability to deploy key immunomodulatory cytokines has emerged as an important risk factor for mortality.

The calorie-rich environment of the modern world is leading to poorer diets for many people. Excess calories contribute to inflammation throughout the body, early-onset of age-related diseases/mortality and a shorter life expectancy. Extreme calorie restriction, 50% below recommended daily limits, may increase lifespan beyond current levels. However, for many people, this is not a price worth paying. Can drugs allow us to achieve greater longevity without severe calorie restriction?

In a previous article about durotaxis, we discussed how cell movements can be guided by elasticity cues at the cell-substrate interface. Here, we focus on the process of cell migration following biochemical cues and the clinical benefits promised by this developing area of research.

The distinction between peptides and proteins is not always apparent, but it is important to understand. Peptides and proteins are, indeed, fundamentally the same, each being composed of amino acids held together by peptide bonds. However, fundamental differences between proteins and peptides go beyond an arbitrary length threshold. Look closer and they differ in structure, function, and therapeutic use.

The immune response is orchestrated. There are mechanisms to activate and deactivate activities. Myeloid-derived suppressor cells (MDSCs) are immune cells that act as regulators of immune responses. They are important in several diseases including tumor growth and the response to cancer therapies, Graft-Versus-Host Disease (GVHD), various autoimmune diseases, and COVID-19. Novel drugs developed to modulate MDSCs are showing promise with ongoing clinical trials for COVID-19 and some cancers.

Among the five classes of therapeutics, peptides represent a unique niche of pharmaceutical compounds within the protein class. The excitement surrounding peptide therapy arises from their distinct physical and biochemical features that present an opportunity for therapeutic intervention that can specifically target a wide range of cells and manipulate their response on a molecular level. However, challenges around their pharmacokinetics, notably poor stability have hampered more widespread use. Addressing these issues will release a new wave of drugs for urgent medical challenges such as anti-microbial resistance.