Project 2 Publications
Project 2 Overview
Single Cell Micro/Nano-ImmunoChip for Cytotoxic T Lymphocyte Mediated Cancer Immunotherapy
Refined through thousands of years of evolutionary advancement, the immune system has developed elegant strategies to defend the body against foreign pathogens and disease targets. One of these mechanisms involve cytotoxic T lymphocytes (CTLs). These T cells are a subset of white blood cells found in peripheral blood, lymph nodes, thymus and spleen. They are distinguished from other cells types by their unique expression of the surface marker CD8. CTLs are so named for their ability either directly or indirectly through biochemical cascades to produce targeted cell death. Each CTL expresses a slightly different T cell receptor (TCR), which recognizes a particular peptide sequence sequestered within the Major Histocompatibility complex (pMHC) on target cells. All cells constantly present digested protein fragments representative of the cellular proteome as a pMHC. The peptide is 7-10 amino acids long and provides sufficient information for the immune system to differentiate between the health state and identity of cells. For example, cells whose control over their own translational machinery that has been usurped by viruses will display “foreign” pMHC, which the immune system recognizes as a breach and launches a series of responses eventually leading to the elimination of the disease target. In similar fashion, T cells can recognize cancer antigens. These peptide sequences are either unique (derived from oncogenetic mutations) or self antigens (derived from chronic activation of oncogenes or signal transduction pathways). By maintaining a large dynamic library of different TCRs, a small population of CTLs exist that can induce cell death in cancer cells by recognizing cancer specific pMHC complexes. The ability to harness and augment this specialized killer CTL to launch a persistent, effective, and specific anti-tumor response remains a promising goal in cancer immunology.

