(Selected Tables and Figures referenced, but not present in this blog
can be found in their corresponding Science Version blogs)
A branch of immunotherapies of profound importance is that of organ, tissue, and cell transplantation. So too are the profound immunological challenges presented in such therapies. All of the considerations of innate and adaptive immunity come into play with homograph, aka allograph transplantation, that is transplantation from one donor to another of the same species (humans for this discussion) but with different genetic (genotype) makeup. Between the basic immunologic tenet of “self-versus-non-self” to the memory response of the immune system, success with homographic transplantation needs intricate blood typing for cellular receptor identification, and genetic matching of donor and recipient.
Organ failure (heart, liver, kidneys, etc.) is not unusual in humans, no less tissue injury and destruction by dermatological diseases (autoimmune and otherwise, e.g., accidents, and particularly, burns). So, the need to reduce or suppress the immune system’s natural reaction to a “foreign transplant” was an obvious necessity in homographic transplantation. Immunosuppressive drugs, from steroids to the strongest immunotherapeutic agents, proved capable of doing the job of controlling the immune response. The introduction of the immunosuppressant drug cyclosporine in 1983 revolutionized transplant medicine. But needless to say, these drugs would also reduce the patient’s fundamental (T cell, B cell, etc.) immune defenses against other non-self-invaders, particularly opportunistic infectious agents.
A group of autoantigens (i.e., self) called isoantigens (blood antigens or HLA complex, all slightly different in individuals) are present in some members of the human species (subset) and not others. Blood transfusion or organ or tissue transplantation of isoantigens into a donor without isoantigens will produce an immune antibody response and result in a severe reaction or graft rejection. So, it is critical that donor blood types and isoantigens are properly matched with recipients.
The discovery of isoantigens led to a more dynamic form of transplantation, namely bone marrow transplant. Given that the bone marrow is a principal site of stem cell, blood cell, and immune cell development, its value in providing a “new” immune system to a qualified recipient with an isoantigen match is of obvious value in treating autoimmune diseases and cancers. Bone marrow transplants may use cells from your own body, called autologous transplant, or from a donor, called allogeneic transplant. In either case, with a proper donor, the stem cells will yield a new, hopefully revitalized and disease-free immune system. By combining these newly developed immunotherapeutic procedures, new treatment modalities including animal to man or “xenotransplantation,” may be viable alternatives to allogeneic transplantation. Recently, a pig heart genetically modified by CRISPR-Cas9 (discussed in Blog #26) was successfully implanted in a 57-year-old male who survived for 2 months. According to the attending surgeons, heart failure resulted from a number of factors. As of this writing, there are no surviving xenotransplant patients.
Comments