A novel lipidic peptide with potential to promote balanced effector-regulatory T cell responses

Abstract

T cell-dendritic cell (DC) interactions contribute to reciprocal stimulation leading to DC maturation that results in production of interleukin-12 (IL-12) and interferon-gamma (IFN-γ). Both cytokines have been implicated in autoimmune diseases while being necessary for effective immune responses against foreign antigens. We describe a lipidic peptide, designated IK14004, that modifies crosstalk between T cells and DCs resulting in suppression of IL-12p40/IFN-γ production. T cell production of interleukin-2 (IL-2) and IFN-γ is uncoupled and IL-12p70 production is enhanced. IK14004 induces expression of activating co-receptors in CD8+ T cells and increases the proportion of Foxp3-expressing CD4+ T regulatory cells. The potential for IK14004 to impact on signalling pathways required to achieve a balanced immune response upon stimulation of DCs and T cells is highlighted. This novel compound provides an opportunity to gain further insights into the complexity of T cell-DC interactions relevant to autoimmunity associated with malignancies and may have therapeutic benefit.

Exploring the efficacy and safety of anti-BCMA chimeric antigen receptor T-cell therapy for multiple myeloma: Systematic review and meta-analysis

“…[ 31 ] Incorporating CD28 signaling domains in CAR design enhances T-cell activation and persistence, with cytokine production sustaining the anti-tumor immune response. [ 33 - 37 ] These results reaffirm anti-BCMA CAR T-cell therapy’s potential to advance MM treatment [ 31 ] significantly.…”

“…This approach stimulates cytokine production, sustaining the anti-tumor immune response, and fostering improved overall patient survival. [ 37 ] Honikel and Olejniczak [ 36 ] showed that illuminating the significance of CD28 allows an understanding of its role as a potent costimulatory signal for T-cell activation and function. The interactions between CAR design and T-cell biology outline the therapy’s multifaceted effectiveness in combating MM.…”

“…As a result, patients treated with anti-BCMA CAR T-cells containing CD28 signaling domains experience improved overall responses, with a more significant proportion of MM cells being targeted and eliminated. [ 37 , 38 ]…”