Chemical Tools To Monitor and Manipulate Adaptive Immune Responses

Abstract

Methods to monitor and manipulate the immune system are of enormous clinical interest. For example, the development of vaccines represents one of the earliest and greatest accomplishments of the biomedical research enterprise. More recently, drugs capable of “reawakening” the immune system to cancer have generated enormous excitement. But, much remains to be done. All drugs available today that manipulate the immune system cannot distinguish between “good” and “bad” immune responses and thus drive general and systemic immune suppression or activation. Indeed, with the notable exception of vaccines, our ability to monitor and manipulate antigen-specific immune responses is in its infancy. Achieving this finer level of control would be highly desirable. For example, it might allow the pharmacological editing of pathogenic immune responses without restricting the ability of the immune system to defend against infection. On the diagnostic side, a method to comprehensivel y monitor the circulating, antigen-specific antibody population could provide a treasure trove of clinically useful biomarkers, since many diseases expose the immune system to characteristic molecules that are deemed foreign and elicit the production of antibodies against them. This perspective will discuss the state-of-the-art of this area with a focus on what we consider seminal opportunities for the chemistry community to contribute to this important field.

A screening platform based on epitope editing for drug discovery

“…Immune responses could play double-edged roles, with a good role of fighting off invading organisms and a bad role of causing autoimmune diseases. 42 Our platform could screen for molecules that may strengthen antibody-antigen interaction to avoid immune escape of antigens, or block epitopes that inhibit innate immune attack in autoimmune diseases. Also, this versatile platform could be used to screen epitope or antibody mimics; 3) screening for imaging agents.…”

“…5) assisting in genome editing: although genome editing is a powerful tool to manipulate disease conditions, the gene associations of some diseases are still elusive, such as the majority of late onset Alzheimer's disease; 43 therefore, epitope editing (immune editing) could be an important complement in genome editing. 42 The SPEED strategy also has certain limitations. For example, prior knowledge of epitope region within an antigen is needed and the corresponding antibodies should be available.…”

Peptides for Infectious Diseases: From Probe Design to Diagnostic Microarrays

“…With this approach the authors are able to identify and further develop sequences or peptidomimetics that bind in the low nanomolar range. These approaches and their subsequent application in therapy and diagnostics are described at length in Doran et al [46]…”

Site-specific C-terminal dinitrophenylation to reconstitute the antibody Fc functions for nanobodies

“…Redirecting these antibodies to target specic disease cells could lead to adaptive immunities for selective and effective therapy. [31][32][33][34][35][36][37] For instance, a pioneering work from McNaughton's group demonstrated that DNP-modied nanobody 5F7 could recruit anti-DNP antibodies to HER2 + cancer cells and elicit a specic ADCC effect in vitro. However, no in vivo studies have been reported yet.…”