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Novel Therapeutic Approaches to Allosensitization and Antibody-mediated Rejection

Jordan, Stanley C., MD1; Ammerman, Noriko, PharmD1; Choi, Jua, PharmD1; Huang, Edmund, MD1; Peng, Alice, MD1; Sethi, Supreet, MD1; Najjar, Reiad, MD1; Toyoda, Mieko, PhD1; Lim, Kathlyn, PharmD1; Louie, Sabrina, MPH1; Vo, Ashley, PharmD1

doi: 10.1097/TP.0000000000002462
Reviews

Modification of pathogenic antibodies for autoimmune diseases illuminated the biologic relevance of B cells, plasma cells, and pathogenic antibodies in autoimmunity. They have also rejuvenated interest in how B cells mediate multiple effector functions that include antibody production, antigen presentation to T cells, costimulation, and the production of immune stimulating and immune modulatory cytokines. Repurposing these drugs from autoimmunity and cancer immunotherapy has yielded important advancements in the care of antibody-mediated rejection patients and novel drug development aimed at HLA desensitization have recently emerged. We now stand on an important threshold that promises many advances in the care of our allosensitized patients. We hope that these initial advances will encourage basic scientist, clinical investigators, industry, National Institutes of Health, our academic societies, and the Food and Drug Administration to continue support of these important objectives. These advances clearly have implications for sensitized patients receiving solid organ transplants and antibody-mediated rejection treatment. Modification of alloimmunity and alloantibodies will also have relevance to xenotransplantation where the xenoantibodies present a formidable obstacle to advancement of this important therapy. Working together, we can advance transplant therapeutics where biologic agents are likely to play novel and important roles. Here, we discuss novel drugs emerging in this area.

In order to improve results in desensitizing hyperimmunized kidney transplant recipients, the authors review not only the role of “classical” drugs but also the one of the many new drugs that will modify the management of this high immunological risk patients.

1 Comprehensive Transplant Center, Transplant Immunotherapy Program, Cedars-Sinai Medical Center, Los Angeles, CA.

Received 27 June 2018. Revision received 15 August 2018.

Accepted 8 September 2018.

S.C.J. received grant support from Hansa Medical, CSL-Behring, Vitaeris, and Genentech and is a consultant for Hansa Medical, CSLBehring, and Genentech. E.H., A.V, J.C., A.P., S.S., R.N, M.T., K.L, S.L, and N.A. have no disclosures to report.

S.C.J. participated in the conception, design, and supervision of work, acquisition and analysis of data, preparation of draft, critical revisions to, and final approval of the article. N.A. conducted the literature evaluation, preparation of draft and revisions to the article. M.T. participated in the conception, design and performance of work, acquisition and analysis of data, and contribution to the preparation of the article. E.H., A.V, J.C., A.P., S.S., R.N, K.L, S.L. participated in the conception, design and performance of work, and contribution to the preparation of the article.

Correspondence: Stanley C. Jordan, MD, Nephrology and Transplant Immunology, Kidney Transplant Program, Cedars-Sinai Medical Center, 8900 Beverly Blvd., West Hollywood, CA 90048. (sjordan@cshs.org).

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