Great strides have been made in recent years in the engineering of immune cells for cancer immunotherapy. In particular, the engineering of T cells to express chimeric antigen receptors (CARs) directed against CD19 has led to remarkable rates of complete remissions (CRs) in different hematological malignancies and subsequent breakthrough FDA approvals of two CAR-T products. However, many challenges remain. Treatment is cumbersome, expensive, and difficult to scale up. Response to treatment is associated with a high risk for severe side effects and a significant proportion of patients relapse. In addition, the application of T cell engineering for the treatment of solid tumors is complicated by the paucity of well-characterized tumor specific antigens and by the immunosuppressive tumor microenvironment.

The emerging field of immune gene therapy aims to tackle these challenges by employing cutting-edge technologies of viral and nonviral vectorology, genome editing and protein design, as well as advanced clinical protocols for adoptive T cell therapies and immune modulation. Immune gene therapy may be applied for the treatment or prevention not only of cancer, but also autoimmune diseases, pathogenic infections, and primary immunodeficiencies. Realizing the full promise of immune gene therapy will thus require the combined efforts of a dedicated community. Human Gene Therapy aims to contribute to this task by publishing a special issue.

The Human Gene Therapy special issue on “Immune Gene Therapy” aims to provide a collection of manuscripts in the following general categories:

• Clinical updates in immune gene therapy of hematological malignancies
• Fighting solid tumors with engineered lymphocytes
• Nonviral vectors and transposons for immune gene therapy
• Genome editing in lymphocytes
• Allogenic therapy with engineered lymphocytes
• Engineering lymphocytes to prevent or clear infections
• Immune gene therapy for autoimmune diseases
• Safety switches and controlled expression in inmune gene therapy