Cell-mediated therapies

Therapy of Mast Cell Mediator-Induced Symptoms... 

Aboody KS, Najbauer J, Danks MK (2008) Stem and progenitor cell-mediated tumor selective gene therapy. Gene Ther 15 739-752... 

Cromolyn and nedocromil are inhaled anti-inflammatory agents that block both the early- and late-phase response. Both agents are considered alternative therapies to inhaled corticosteroids for the treatment of mild persistent asthma however, both are less effective than low doses of inhaled corticosteroids.2,30 The exact mechanism of action of these agents is not understood, but they appear to inhibit mast cell mediator release as well as modulate other inflammatory responses.3... 

Also known as antibody-mediated rejection, humoral rejection is the process of creating graft-specific antibodies.1,4 This type of rejection occurs less frequently than cell-mediated acute rejection. Humoral rej ection is characterized by deposition of immunoglobulins and complement in allograft tissues. Treatment for this type of rejection is not well defined, yet several reports have shown that treatments such as plasmapheresis, immunoglobulin therapy, rituximab, and/or antithymocyte globulin maybe effective. 

The improved short-term outcomes gained from induction therapy come with a degree of risk. By using these highly immunosuppressive agents, particularly the antilymphocyte antibodies (ALAs), muronomab-CD3 (OKT-3), and the antithymocyte antibodies, the body loses much of its innate ability to mount a cell-mediated immune response, which increases the risk of opportunistic infections and cancer.7,10... 

Secondary prophylaxis or suppressive therapy is recommended for endemic mycoses in immunocompromised patients, especially in hosts with pronounced defects in T-cell-mediated immunity (i.e., AIDS). 

Invasive molds, particularly Aspergillus, have become an increasingly important complication of cancer therapy and organ transplantation. Patients with acute leukemia and recipients of allogeneic hematopoietic cell transplants are at especially high risk for invasive aspergillosis due to prolonged neutropenia and deficiencies in cell-mediated immunity associated... 

Antibodies have and likely will find additional use in transplantation-related medicine. In general, cell-mediated immunological mechanisms are responsible for mediating rejection of transplanted organs. In many instances, transplant patients must be maintained on immunosuppressive drugs (e.g. some steroids and, often, the fungal metabolite cyclosporine). However, complications may arise if a rejection episode is encountered that proves unresponsive to standard immunosuppressive therapy. Orthoclone OKT-3 was the first monoclonal antibody-based product to find application in this regard. 

The anthelmintic agent levamisole increases delayed hypersensitivity and T-cell mediated immunity. It has been used as adjuvant therapy for colorectal cancer. A recent Cochrane review concluded that... 

Pneumocystis carini pneumonia (PCP), the most common of the opportunistic infections, occurs in more than 80% of AIDS patients (13). Toxoplasmosis, a protozoan infection of the central nervous system, is activated in AIDS patients when the CD4+ count drops and severe impairment of cell-mediated immunity occurs. Typically, patients have a mass lesion(s) in the brain. These mass lesions usually respond well to therapy and can disappear completely. Fungal infections, such as Cyptococcalmeningitis, are extremely common in AIDS patients, and Histoplasma capsulatum appears when cell-mediated immunity has been destroyed by the HIV virus, leading to widespread infection of the lungs, liver, spleen, lymph nodes, and bone marrow. AIDS patients are particularly susceptible to bacteremia caused by nontyphoidal strains of Salmonella. Bacteremia may be cleared by using antibiotic therapy. 

Moutsatsos, I.K., Turgeman, G., Zhou, S., Kurkalli, B.C., Pelled, G., Tzur, L. et al. (2001) Exogenously regulated stem cell-mediated gene therapy for bone regeneration. Mol. Ther., 3,449 161. 

Levamisole was first synthesized for the treatment of parasitic infections. Later studies suggested that it increases the magnitude of delayed hypersensitivity or T cell-mediated immunity in humans. In immunodeficiency associated with Hodgkin s disease, levamisole has been noted to increase the number of T cells in vitro and to enhance skin test reactivity. Levamisole has also been widely tested in rheumatoid arthritis and found to have some efficacy. However, it has induced severe agranulocytosis (mainly in HLA-B27-positive patients), which required discontinuation of its use. The drug may also potentiate the action of fluorouracil (5-FU) in adjuvant therapy of colorectal cancer, and this combination has been approved for clinical use in the treatment of Dukes class C colorectal cancer after surgery. Its use in these cases reduces recurrences, and the mechanism... 

A myriad of preclinical and first-in-man clinical studies suggest that cell therapy has a positive effect on cardiac and vascular repair. In fact, in most studies, the tested cell types were found to be effective, even in the absence of the evidence of robust cell engraftment. This unexpected outcome defines how little we actually understand at present about the underlying mechanism ) of cell-mediated repair, We attribute much repair to direct participation of the transplanted cells in angiogenesis or myogenesis, but in truth, despite promising clinical outcomes, relatively little clinical data exist to support this contention. 

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