The novel immunotherapeutic molecule T11TS modulates glioma-induced changes of key components of the immunological synapse in favor of T cell activation and glioma abrogation

Abstract

T-cell-mediated immune responses are typically low in conditions of malignant glioma which has been known to cause marked immunesuppression and dysregulate major T-cell signaling molecules. Thus, T-cell-based immunotherapies are currently in vogue in the treatment of malignant glioma. The novel glycopeptide, T11TS/S-LFA-3/S-CD58 has previously been shown by our group to be highly efficacious in glioma abrogation in in vivo and in vitro conditions. This glycopeptide ligands to the costimulatory CD2 molecule on T-cells, causing profound immune stimulation leading to glioma abrogation, suggesting probable involvement of T11TS in modulation of the T-cell signaling pathway. The present study offers a multi-targeted approach towards repair of some of the key components of the immunological synapse at the T-cell-APC interface and is therefore the first of its kind to offer a holistic model of restoration of immunological synapse components so as to trigger T-cells towards activation against glioma. The study thus indicates that the totally dysregulated molecular events at the immunological synapse in glioma are restored back to normal levels with the administration of T11TS, which finally culminates in glioma abrogation. The present study thus delineates an important T-cell signaling approach whereby T11TS acts as an anti-neoplastic agent, thus helping to chart out newer avenues in the fight against gliomas.

T11TS immunotherapy augments microglial and lymphocyte protective immune responses against Cryptococcus neoformans in the brain

“…All nucleated cells express MHC class I molecules, but MHC class II molecules are found only on antigen‐presenting cells, which bind to peptides derived from degradation of cytosolic proteins and extracellular proteins, respectively. The interaction between MHC I:peptide is recognized by cytotoxic T cells (CTLs) and MHC II molecules are being recognized by CD4 helper T cells …”

“…10 000 events were acquired and analysed for each sample. Values indicated in “Results” are the mean of six individual studies with SD calculated on each mean value …”

“…Bonferroni's post hoc test was applied to the data: a value of P < 0.05 following this post hoc procedure was considered statistically significant. All results were evaluated statistically by applying the GraphPad Prism software (Prism 4 for Windows, Version 4.03, Corning, NY, USA) …”

“…T11TS‐mediated actions have direct consequences in rejuvenating the immune defence, with increased immune cell phenotypic expressions, antigen presentation and cytokine regulation in the brain compartment to overcome the immune suppression status . T11TS causes activation of important components of the T cell‐antigen‐presenting cell (APC) of the immunological synapse and trigger the activation of T cell . Previous publications with T11TS have proposed that in glioma‐bearing rats, T11TS promotes proliferation of the T cells and also favours the T cell survival by inhibition of apoptosis through both the extrinsic and intrinsic apoptotic pathways .…”

Tumor microenvironment as a target of malignant gliomas treatment

“…Соответственно, остается открытым вопрос, бу-дет ли одного подавления М2-фенотипа без последующе-го восстановления М1-фенотипа достаточно для контроля опухолевого роста не только на доклинических моделях, но и у пациентов с МГБ. Новый иммунотерапевтический агент гликопептид T11TS, представляющий из себя лиганд к костимуля-торному рецептору CD2 на Т-клетках, также проде-монстрировал противоопухолевую активность [46]. Она была обусловлена с одной стороны иммуно-опо-средованным апоптозом опухолевых клеток, а с другой стороны негативной модуляцией экспрессии матрикс-ных металлопротеиназ 2 и 9 (ММР-2, -9), интегрина ,…”