POTENSI KOEKSPRESI CHIMERIC ANTIGEN RECEPTOR (CAR) DAN GEN FOXP3 PADA SEL T REGULATORS SEBAGAI MODALITAS TERAPI PENATALAKSANAAN AUTOIMUN

Abstract

Introduction: Autoimmune disease is immune response that damages self-tissues and disrupts physiological
functions of the body. The prevalence of autoimmune diseases has continued to increase globally since World War
II. In US, this disease is the leading cause of death and commonly seen in women. Conventional autoimmune
medicine suppresses most of immune system and causes patients to be more susceptible to opportunistic infections
and cancer. Based on these facts, therapeutic innovations that are specific to pathological immune cells are needed.
Molecular therapy using stable, target-specific Tregs engineered is potential as the latest modality for autoimmune
therapy.
Discussion: Autoimmune occurs when adaptive immune response attacks self-antigens. The autoimmune
mechanism is then followed by activation of a large number of T cells. All activated T cells are controlled by T
regulators or Tregs. Tregs have weaknesses which are low selectivity and stability. For this reason, Treg
engineering with selective receptor expression and Treg stabilizer is needed. The selective receptors that can be
modified with T cells are Chimeric Antigen Receptor (CAR). CAR is known to selectively inhibits pathological
immune responses and stops inflammation. CAR is combined with Treg stabilizer which gives the effect of
amplification and stabilization, that is Forkhead box P3 (FoxP3). FoxP3 is core protein that functions as the main
regulator of Tregs development and self-tolerance.
Conclusion:CAR/FoxP3-Engineered Tregs express FoxP3 that have strong affinity for self-antigens through CAR
receptors. The application of CAR/FoxP3-Engineered Tregs increases the selectivity and stability of Treg cells to
supress autoimmune.