Enhancing Efficacy of TCR-engineered CD4 + T Cells Via Coexpression of CD8α.

Adoptive cell therapy with T cells expressing affinity-enhanced T-cell receptors (TCRs) is a promising treatment for solid tumors. Efforts are ongoing to further engineer these T cells to increase the depth and durability of clinical responses and broaden efficacy toward additional indications. In the present study, we investigated one such approach: T cells were transduced with a lentiviral vector to coexpress an affinity-enhanced HLA class I-restricted TCR directed against MAGE-A4 alongside a CD8α coreceptor.

Defective Monocyte Enzymatic Function and an Inhibitory Immune Phenotype in Human Immunodeficiency Virus-Exposed Uninfected African Infants in the Era of Antiretroviral Therapy.

Background: Human immunodeficiency virus-exposed uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa and are highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated whether human immunodeficiency virus (HIV)-exposure dysregulates HEU immunity, vaccine-antibody production, and human herpes virus amplify this effect.

Engineering Cancer Antigen-Specific T Cells to Overcome the Immunosuppressive Effects of TGF-β.

Adoptive T cell therapy with T cells expressing affinity-enhanced TCRs has shown promising results in phase 1/2 clinical trials for solid and hematological tumors. However, depth and durability of responses to adoptive T cell therapy can suffer from an inhibitory tumor microenvironment. A common immune-suppressive agent is TGF-β, which is secreted by tumor cells and cells recruited to the tumor.

Early T Cell Differentiation with Well-Maintained Function across the Adult Life Course in Sub-Saharan Africa.

Immune senescence is a significant contributor to health problems in the developed world and may be accelerated by chronic viral infections. To date, there have been few studies of immune function in healthy older people in sub-Saharan Africa. We assessed T cell and B cell phenotypes and immune responses to CMV, EBV, and influenza virus in Malawians aged 20-69 y.

Cytomegalovirus-Specific T Cells Restricted by HLA-Cw*0702 Increase Markedly with Age and Dominate the CD8 T-Cell Repertoire in Older People.

Cytomegalovirus (CMV) infection elicits a strong T-cell immune response, which increases further during aging in a process termed "memory inflation." CMV downregulates the expression of HLA-A and HLA-B on the surface of infected cells to limit presentation of viral peptides to T-cells although HLA-C is relatively spared as it also engages with inhibitory killer immunoglobulin receptor receptors and therefore reduces lysis by natural killer cells. We investigated the magnitude and functional properties of CMV-specific CD8 T-cells specific for 10 peptides restricted by HLA-C in a cohort of 53 donors between the age of 23 and 91 years.