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Immunoengineering is a broad field that encompasses immunotherapy, immunoediting, and immunomodulation. The common thread between sub-fields of immunoengineering is that the immune system is the key to the target treatment, whether by exploiting its natural processes or altering its function by synthetic routes.

Within immunoengineering, immunotherapy refers to any cancer treatment meant to assist the immune system in recognizing or attacking cancer cells^[1]. Immunoediting refers to the human body’s tumor suppression mechanism^[2]. While it often is used in the context of cancer treatment, it can be applied to other diseases as well. Immunomodulation is a broad term referring to any substance used to heighten or suppress immune system function^[3].

Immunoediting, specifically in the context for cancer treatment, is the process which involves immune cells manipulating the immune response that developing tumors may invoke.^[2] The ability to edit the immune response invoked by developing tumors has been experimented and concluded to be an ability capable of innate immunity to some extent, and further enhanced by the presence of adaptive immunity.^[2] Immunoediting, primarily discussed within the context of cancer, occurs through three phases that may be known as elimination, equilibrium, and escape.^[4] Within HIV, a selection for mutations experienced by HIV-infected cells allows for escape from an immune response made to eliminate the infected cell, similar to how some tumors escape the immune response within cancer immunoediting.^[5] The selection experienced within HIV is one in which infected cells demonstrating viral latency may have been selected for the resistance to elimination from corresponding T cells. COVID-19 is additionally stated to have developed immune evasion mechanisms that allow for COVID-19 symptoms to persist within individuals.^[5] Such mechanisms are stated to be potentially attributed to the pressures that are selected for by the immunoediting response that may occur between the immune system and the Covid-19 virus. It is these mechanisms that involve making the virus invisible to the immune system or locating the virus in an anatomical area inaccessible to the immune cells meant to eliminate the virus, similar to how cancer cells persist within cancer immunoediting.

Autoimmune disorders are defined as conditions where the adaptive immune system mistakenly attacks healthy tissue, mounting an immune response. There are over 100 types of autoimmune disorders that affect 3-5% of the global population.^[6] Treatments for autoimmune disorders, if present, rely on the use of immunosuppressive drugs, broadly reducing immune system activity which are not curative measures and increase susceptibility to infection. Immunoengineering is an approach that is being investigated as a form of targeted treatment for autoimmune disorders.^[7]

Chimeric antigen receptor T (CAR-T) cell therapies, originally developed for the treatment of blood cancers, have been studied as pre-clinical models for the treatment of autoimmune disorders. CAR-T cells are autologous T lymphocytes harvested from the patient and are genetically engineered to target specific disease-causing cells.^[8]

B lymphocytes are a common target for CAR-T cell therapy because they produce antibodies that cause tissue damage. Early clinical trials have shown that CAR-T cell mediated B lymphocyte depletion has resulted in remission of life-long autoimmune diseases.^[8] In systemic Lupus Erythematosus (SLE), inflammatory tissue damage is driven by autoreactive B cells that target the body’s own cells. Clinical studies have demonstrated the depletion of B lymphocytes using CD19-directed CAR-T cell therapies to produce meaningful remission of SLE.^[9]

Type 1 diabetes (T1D) is one of the most prevalent autoimmune disorders, affecting 9.5 million people globally as of 2025.^[10] T1D occurs when the immune system attacks and destroys the insulin-producing beta cells within the pancreas. While the current standard treatment for T1D is insulin replacement therapy, CAR-T cell therapies as preclinical models are being designed to recognize pancreatic beta cells and release anti-inflammatory cytokines to suppress unwanted autoimmune response.^[11]

A developing method is the transplantation of pancreatic islet cells, which requires the subsequent use of immunosuppressive drugs to prevent transplantation rejection.^[12] Immunoengineering therapies for T1D focus on protection of the transplanted islet cells using encapsulation, shielding the transplanted cell from the body’s immune system while allowing for the passage of insulin and nutrients.^[13] Biomaterials are also designed to locally deliver immunomodulatory agents to specifically target immune response at the site of beta islet transplantation. While successful in small animal models, limitations such as fibrotic overgrowth and minimal graft stability remain barriers to the large animal clinical implementation of this method.^[13]

In attempting to treat tumors, vaccines, specifically the In situ vaccine, have dealt with the problems of immunosuppression and immunogenicity scarcity attributed to the tumor.^[14] A tumor-activated and optically reinforced immunoscaffold, known as TURN, was constructed to manipulate the phases of cancer immunoediting and allow for more effective treatment against the tumor. This effective treatment firstly involves the release of RGX-104 proteins that are released in response to tumoral reactive oxygen species. These proteins work to weaken the cells and cytokines of the tumor that are responsible for the immunosuppression attributed to the tumor that works against the body’s natural immune system response to combat the tumor. Afterwards, agents of TURN are activated with a laser which then triggers the tumor to expose its antigens, allowing for the T-cells to invade the tumor. CD137 agonists from the scaffold work to promote the work done from the T-cells attacking the tumor through improved efficiency of T-cells through survival, function, and proliferation. In summary, the scaffold allows for the tumor’s immunosuppression properties to be combated which then expose the escaped or hidden antigens, allowing for T-cells to reach equilibrium with them before majorly eliminating the tumor cells through aid by the CD137 agonists. This speaks to the reverse cancer immunoediting nature of the scaffold, for instead of allowing the tumor cells to first experience initial elimination, equilibrium, and then escape from the immune response, the escaped tumor cells are brought out from their escape to be combated into equilibrium, to then be fought further into effective elimination.