PROMOTION OF A LOCALIZED TOLEROGENIC MICROENVIRONMENT USING TolAPC PARTICULATE SYSTEMS
Embargo until
2022-08-01
Date
2020-08-27
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Publisher
Johns Hopkins University
Abstract
There are many life-threatening conditions for which transplantation offers a way to extend longevity and vastly improve the quality of life. Although transplants can be crucial in some cases, the degree and duration of success can vary greatly. Much of this is due to protective immunity, which targets any foreign material that enters the body—including transplanted cells and tissue. Biomaterials have been employed to isolate exogenous tissues from the host immune system and increase transplant acceptance, and numerous other techniques are also used to improve patient outcomes including transplant location, what condition the organ is used in (whole or as functional subunits), and administration of immunosuppressives. While advances in transplant technology have improved patient outcomes, they have also come with their own drawbacks. Longer donor recipient waiting lists as supply has not caught up with demand, reactions to protective biomaterials, and adverse effects of chronic immunosuppressives all hinder the field. These considerations and others point to finding a solution that eliminates the need for resident biomaterials to avoid a tangential reaction to the material while promoting a localized environment the transplanted tissue can survive in long-term. Antigen presenting cells are a class of immune cells that indirectly influence the differentiation of naïve T cells. Artificial antigen presenting cells (aAPCs) are the fabricated counterpart to APCs, designed exogenously and administered to patients. This allows for greater control over how they affect T cell differentiation. A new type of aAPCs, called tolerogenic aAPCs (TolAPCs), are specifically focused on generating a tolerogenic response by inducing regulatory T cells (Tregs), able to both destroy and suppress effector T cell populations. Taking advantage of this mechanism to reduce the activity of these effector populations can be used to promote acceptance of both biomaterials and cellular transplants. The immunosuppressive ability of TolAPCs is of particular interest to this study. The intention is to use TolAPCs to promote a localized immunosuppressed microenvironment in vivo via induction of Tregs, whether it be proliferation and/or increased migration and infiltration into local tissue, to allow for cellular transplantation without the use of long-term biomaterials.
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Keywords
Tolerogenic, artificial APC, aAPC, TolAPC, Type 1 Diabetes, T1D, PLGA, PBAE, transplant