Immune engineering merges immunology with bioengineering to enhance immune functions. It aims to boost responses against pathogens and tumors, while suppressing unwanted reactions in autoimmune diseases. This field develops better vaccines and tailors treatments to individual patients.

Synthetic immunology applies synthetic biology to create artificial immune components. It enables precise control over function and specificity, allowing for customizable immune responses. Applications include engineered antibodies, synthetic cytokines, and programmable immune cells for targeted therapies.

Fundamentals of Immune Engineering and Synthetic Immunology

Goals of immune engineering

• Immune engineering combines immunology, bioengineering, and molecular biology to manipulate and enhance immune system functions
• Enhance immune responses against pathogens and tumors through targeted activation strategies (checkpoint inhibitors)
• Suppress unwanted immune reactions in autoimmune diseases and transplantation using immunomodulatory approaches (regulatory T cells)
• Develop more effective vaccines and immunotherapies by optimizing antigen presentation and immune cell activation (mRNA vaccines)
• Create precision medicine approaches tailoring treatments to individual patients' immune profiles (neoantigen vaccines)
• Modulation techniques employ genetic modification of immune cells, nanoparticle-based drug delivery systems, and biomaterial scaffolds for controlled immune cell activation

Principles of synthetic immunology

• Synthetic immunology applies synthetic biology principles to immunology creating artificial immune components and systems
• Rational design of immune components enables precise control over function and specificity (bispecific antibodies)
• Modular assembly of immune system parts allows for customizable and tunable immune responses (CAR-T cells)
• Predictable and controllable immune responses achieved through engineered feedback loops and regulatory circuits
• Applications include engineered antibodies with enhanced specificity and efficacy, synthetic cytokines with improved pharmacokinetics, artificial antigen-presenting cells for T cell activation, and programmable immune cells for targeted therapies (NK cell engagers)

Advanced Techniques and Considerations

Gene editing for immune cell engineering

• CRISPR-Cas9 system acts as a programmable DNA-cutting tool allowing precise genetic modifications in immune cells
• Applications involve knockout of inhibitory receptors to enhance T cell function, introduction of chimeric antigen receptors (CARs) into T cells, and modification of cytokine production profiles
• Other gene editing tools include TALENs and Zinc Finger Nucleases (ZFNs) offering alternative approaches for genetic manipulation
• Gene editing in immune engineering increases precision and efficiency compared to traditional methods and enables creation of multiplex modifications

Potential of engineered immune cells

• CAR-T cell therapy engineers T cells to express chimeric antigen receptors targeting specific tumor antigens
• Remarkable success achieved in certain hematological malignancies (B-cell leukemias and lymphomas)
• Ongoing research explores applications for solid tumors and addresses challenges like off-target effects and cytokine release syndrome
• Other engineered immune cells include TCR-engineered T cells, CAR-NK cells, and macrophages enhanced for phagocytosis
• Potential applications extend beyond cancer to autoimmune diseases, infectious diseases, and regenerative medicine

Ethics of immune engineering

• Safety concerns for patients and society arise from potential long-term effects and unintended consequences of genetic modifications
• Equitable access to advanced therapies raises questions about healthcare disparities and resource allocation
• Regulatory challenges involve balancing innovation with safety, developing appropriate clinical trial designs, and harmonizing international regulations
• Societal implications include impact on healthcare costs, public perception, and acceptance of engineered immune therapies
• Intellectual property issues surrounding patenting of engineered immune components and therapies require balancing innovation incentives with public health needs