Antibody-Based Preparative Regimens for Cell, Tissue and Organ Transplantation

Abstract

The ability to successfully transplant cells and organs from a donor into an immunologically disparate recipient is one of the greatest treatment advances in the history of medicine. Nevertheless, acute and chronic rejection, graft versus host disease, and the inability to identify suitable donors continue to be challenges and limit broader application of cell and organ transplantation to the many patients that could benefit. Immunosuppression before and after allogeneic transplant has been found to dramatically improve allograft survival and, despite side effects, has been a mainstay of patient management. Inducing donor-specific tolerance is the holy grail in allotransplantation and is readily established in experimental animals but has been difficult to achieve in patients in settings apart from hematopoietic cell transplantation. Antibody-based conditioning to prepare the recipient is a promising approach towards achieving transplant tolerance in both hematopoietic and solid organ transplant settings, and multiple targets are currently under consideration including those on circulating lymphocytes and hematopoietic stem cells. Here we review progress in the use of antibodies to support cell and tissue transplantation with a particular focus on induction of donor-specific tolerance for solid organ transplantation.

Streptavidin-Saporin: Converting Biotinylated Materials into Targeted Toxins

“…A 2018 review publication summarized the targeted conditioning studies at that point in time [ 41 ]. Griffen et al and Van Hentenryck et al have both summarized the current status of antibody-based drugs in pre-transplant conditioning regimes [ 47 , 88 ]. Saporin conjugates that are discussed in their reviews are Anti-CD45-SAP and Anti-CD117-SAP; both were originally created for pre-transplant conditioning utilizing Streptavidin-ZAP [ 43 , 89 ].…”

“…This reaction has been widely studied and described and has proven itself to be an appropriate choice for a modular way of screening targeting agents. It was largely seen as an advantage to have one molecule that can be utilized both in vitro [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ] and in vivo [ 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. This modularity provided researchers the advantage of developing and planning larger-scale projects from preliminary in vitro beginnings to late-stage in vivo behavioral studies, all using the same verified reagent.…”

“…An important aspect of determining when Streptavidin-ZAP is an appropriate method for your screening or behavioral studies is to first calculate the amount you will need. Antibodies have been primarily the targeting agent of choice [ 32 , 34 , 38 , 39 , 40 , 43 , 44 , 45 , 46 , 47 , 56 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ], and conveniently, due to the similarity in molecular weight between whole IgG (~150 kDa) and Streptavidin-ZAP (~136 kDa), a small amount (25 μg) of Streptavidin-ZAP was found to facilitate numerous experiments. It is important to note when the biotinylated targeting agent is smaller in size, specifically in studies done with peptides in the range of 2–6 kDa, the amount of equimolar Streptavidin-ZAP needed is also small (0.37–1.1 μg).…”