Address for Correspondence:
Rajendra Bhimma,
Department Of Maternal & Child Health, Nelson R Mandela School Of Medicine, University Of Kwazulu-Natal, Private Bag 7, Congella, 4013, Durban, South Africa.
E-MAIL: bhimma@ukzn.ac.za

Keywords:
immunosuppression, children, kidney, transplantation

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Maintenance Immunosuppression

C. Novel Immunosuppressant Agents
Several new biological agents are in various stages of development for the purposes of replacing maintenance therapy with calcineurin inhibitors and steroids [7]. Table 2 shows the list of some of these new agents and their status in transplantation.

Table 2 Biologic agents in the transplant pipeline

Antibody	Pharma/Biotech	Status
LEA29Y	Bristol Myers	Phase III trial
Efalizumab*	Xoma-Genetech	Phase II
Alemtuzumab*	Genzyme	IS
Rituximab	Genentech	IS
mIL-5/Fc	Roche	Preclinical
Anti-IL-15	Amgen	Preclinical
Anti-CD40	Bristol Myers Chiron Novartis	Preclinical Preclinical Preclinical
IS - investigator initiated trials. * US Food and Drug Administration (FDA) approved for other indications

Adapted from: Vincenti F, Hirose R. Novel Immunosuppressants. In: Fine RN, Weber SA, Olthoff KM, Kelly DA, Harmon WE, eds. Pediatric Solid Organ Transplantation, 2nd Edition.
Massachusetts USA: Blackwell Publishing Ltd. 2007: 89-94.

Currently, only LEA29YT (belatacept) is in phase III trials. Whilst the co-stimulatory pathway is emerging as an important therapeutic area for immunosuppression therapy, other promising targets include interleukin-15 and adhesion molecules [3].

Costimulation signal is provided by engagement of one or more T-cell surface receptors with their specific ligands on antigen presenting cells. Signaling through the T-cell receptor alone without a costimulatory signal can lead to a prolonged state of T-cell energy [93]. Presently the only agent used in clinical trials in adult kidney transplant recipients, which blocks co-stimulation is belatacept [94]. This agent is typically administered intravenously on a once-per-month schedule. The results showed decreased incidence of acute rejection at 6 months (6-8%), improved glomerular filtration rate at 12 months (62-66ml/1.73m2/min) and decreased incidence of chronic allograft nephropathy. There were 3 episodes of post-transplant lymphoproliferative disease, two of which were related to primary Epstein-Barr virus infection. Thus the concern regarding its use in children is the potentially higher risk of post-transplant lymphoproliferative disease. However, this has to be balanced agents its potential benefit of improving compliance since it is administered monthly, particularly in adolescents.

CONCLUSION

To date the majority of paediatric renal transplant recipients are treated with triple immunosuppression [95]. The increasing number of agents available has increased the number of combinations and to date there are over 60 possible reported protocols [96]. These large number of protocols bear testimony to the fact that there is no single defined approach to immunosuppression for children. The final common goal is to achieve long-term graft acceptance with the fewest possible chronic medication.

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