Modulating T Cell Responses by Targeting CD3

Abstract

Harnessing the immune system to fight cancer has become a reality with the clinical success of immune-checkpoint blockade (ICB) antibodies against PD(L)-1 and CTLA-4. However, not all cancer patients respond to ICB. Thus, there is a need to modulate the immune system through alternative strategies for improving clinical responses to ICB. The CD3-T cell receptor (TCR) is the canonical receptor complex on T cells. It provides the “first signal” that initiates T cell activation and determines the specificity of the immune response. The TCR confers the binding specificity whilst the CD3 subunits facilitate signal transduction necessary for T cell activation. While the mechanisms through which antigen sensing and signal transduction occur in the CD3–TCR complex are still under debate, recent revelations regarding the intricate 3D structure of the CD3–TCR complex might open the possibility of modulating its activity by designing targeted drugs and tools, including aptamers. In this review, we summarize the basis of CD3–TCR complex assembly and survey the clinical and preclinical therapeutic tools available to modulate CD3–TCR function for potentiating cancer immunotherapy.

Targeted pH-Activated Peptide-Based Nanomaterials for Combined Photodynamic Therapy with Immunotherapy

“…Ensuring the production of an ample number of functional T cells, specifically CD3 + cells, is paramount in the context of tumor immunotherapy. − Among these T cells, the CD3 + CD8 + subpopulation, known as cytotoxic T lymphocytes (CTL), possesses the capability to effectively recognize and eliminate tumor cells, whereas the CD3 + CD4 + subpopulation, termed helper T lymphocytes (Th), plays a vital role in orchestrating the antitumor immune response. − The immune responses associated with PRGD/NLG919 nanosheets were scrutinized through FACS. In this experiment, the proliferation of both CD3 + CD8 + T cells and CD3 + CD4 + T cells in peripheral blood mononuclear cells (PBMCs) was assessed under various conditions: PBMC monoculture, PBMCs cocultured with PBS-treated HeLa cells, PBMCs cocultured with PRGD/NLG919 nanosheets-treated HeLa cells without or with 660 nm laser irradiation at 0.12 W cm –2 for 5 min ( n = 3).…”

Direct visualization of immune status for tumor‐infiltrating lymphocytes by rolling circle amplification

“…It is well known that CD3 is a critical molecule present on the surface of T cells, responsible for immune response, and plays a vital role in the activation, expansion, and overall functionality of immune cells [44]. In contrast, interleukin‐10 (IL‐10) is a multifunctional negative regulator involved in the biological regulation of immune cells, inflammatory cells and tumor cells, and it can affect T cell activation and cytokine secretion [45].…”

MDA5 with Complete CARD2 Region Inhibits the Early Replication of H9N2 AIV and Enhances the Immune Response during Vaccination

“…It is well known that CD3, CD4, and CD8 are mainly expressed on the surface of T cells and are CD molecules involved in recognition, adhesion, and activation [31]. CD3 forms a complex with T cell surface receptors and transmits signals into cells to initiate T cell activation [32]. CD4 molecules help to identify antigens presented by MHC class II molecules, and CD8 molecules assist in the identification of antigens presented by MHC class I molecules [33].…”