Role of Cell-Mediated Immunity in Resistance to Malaria
Mary M. Stevenson in Malaria: Host Responses to Infection, 2017
In addition, antibody-independent resistance to assorted hemoprotozoa has been achieved by the injection of various immunomodulating agents.19 The most compelling evidence that nonantibody T cell-dependent immune mechanisms can mediate resistance to malaria has been obtained from studies utilizing B cell-deficient hosts which resolved acute infections 9with blood-stage parasites spontaneously27 or resisted reinfection following chemotherapy.28–30 The finding of Chen et al.31 that B cell-deficient mice immunized with irradiated P. berghei sporozoites were resistant to challenge with viable sporozoites demonstrated that resistance to this stage of the parasite could be mediated by T cell-dependent immune mechanisms as well. The results of adoptive transfer studies employing immune T cells, antigen-specific T cell lines, and T cell clones provide definitive evidence in support of this concept (see below).
Revelations
John Melford in Pocket Guide to Cancer, 2017
Progress is being made with an experimental form of immunotherapy referred to as adoptive cell transfer. It is a common observation that in many forms of cancer, killer cells of the immune system such as macrophages, neutrophils, and cytotoxic T-cells become associated with the tumor microenvironment. Although this demonstrates the ability to recognize tumor cells, it also shows a lack of capability to destroy them. It is assumed molecules released by tumor cells somehow suppress the attacking machinery of killer cells. In one method of treatment, tumor‑associated T-cells are harvested and cloned in a laboratory. They are then energized by exposure to cytokines and infused back into the patient’s bloodstream. The aim of this approach is to provide a boost to the immune system to help it launch an overwhelming attack. Clinical trials have demonstrated this method to be effective in completely eradicating tumors in some patients with very advanced cancer that were primarily cancers of the blood. To improve the effectiveness of adoptive cell transfer, it may be necessary to first obliterate the patient’s immune system with high doses of chemotherapeutic drugs to eliminate suppressed immune cells and to create room for the new fired-up cells.
Immunogenetics and Immunopathogenesis of the NOD Mouse
George S. Eisenbarth in Immunotherapy of Diabetes and Selected Autoimmune Diseases, 2019
Studies utilizing adoptive transfer system showed controversial results regarding T cell subsets involved in the disease transfer. Transfer experiments by Miller and co-workers34 utilizing irradiated young NOD mice as recipients suggested that both L3T4 + and Lyt2 + T cells are necessary for the disease transfer. Neither L3T4 + cells nor Lyt2 + cells alone were able to transfer the disease, but when the two subsets were cotransferred, most recipients developed diabetes. In addition, their data indicated that both subsets must be obtained from diabetic donors. Neither subset can be replaced with cells from young, nondiabetic donors. These data suggest that donor cells must be activated or primed like cells in diabetic animals to transfer the disease.
Redirected optimized cell killing (ROCK®): A highly versatile multispecific fit-for-purpose antibody platform for engaging innate immunity
Published in mAbs, 2019
Kristina Ellwanger, Uwe Reusch, Ivica Fucek, Susanne Wingert, Thorsten Ross, Thomas Müller, Ute Schniegler-Mattox, Torsten Haneke, Erich Rajkovic, Joachim Koch, Martin Treder, Michael Tesar
Adoptive cell transfer is a highly personalized cancer immunotherapy in which patients receive immune cells exerting anticancer activity. These can typically be tumor-infiltrating lymphocytes collected from the patient, expanded and stimulated in vitro before reinfusion, or genetically engineered to express chimeric antigen receptors (CARs), thereby enhancing tumor cell targeting and killing. As with bispecific antibodies, adoptive cell therapy approaches have mainly focused on engaging cytotoxic T cells with antigen-expressing target cells, resulting in T cell activation and subsequent killing of cancer cells expressing those targets. First approvals of CAR T cell (CAR-T) therapies were the CD19-targeting CAR-T axicabtagene ciloleucel (Yescarta®) in large B-cell lymphoma and tisagenlecleucel (Kymriah®) in non-Hodgkin lymphoma and B cell ALL in 2017.
Cellular immunotherapy as a therapeutic approach in multiple myeloma
Published in Expert Review of Hematology, 2018
Jessica Liegel, David Avigan, Jacalyn Rosenblatt
In myeloma, rapid recovery of the absolute lymphocyte count post-ASCT has been associated with improved outcomes. Adoptive cell transfer (ACT) has been developed to increase the availability of immunocompetent effector cells and can be considered at various stages of disease. This involves removal of autologous T cells obtained from peripheral blood via leukapheresis or from the site of disease such as marrow infiltrating lymphocytes (MILs). These cells can be obtained post-vaccination or primed with antigenic stimulus or genetically engineered for specific antigen targets, such as TCR modified T cells or chimeric antigen receptor T or NK cells, see Figure 1. Ex-vivo proliferation is achieved with CD3/CD28 ligation and the target dose is then re-infused into the patient typically following a period of host preconditioning with lymphodepleting chemotherapy that removes suppressor cells and facilitates in vivo expansion.
Safety considerations with current and emerging antiviral therapies for cytomegalovirus infection in transplantation
Published in Expert Opinion on Drug Safety, 2019
Guy El Helou, Raymund R Razonable
Knowledge of the potential interaction of anti-CMV drugs with other medications used in the complex transplant population is highly encouraged, as there may be potential additive and synergistic adverse outcomes. All of these safety variables will need to be considered, in addition to their efficacy profiles (not discussed in detail here), in choosing the best antiviral drug for the prevention and treatment of HCMV in the transplant setting. Finally, the authors recommend that the management of HCMV infection after transplantation should always take into account the fact that this virus became opportunistic as a result of severe impairment in immune function. Thus, we encourage discussing reduction in immunosuppressive drug doses with the multidisciplinary transplant teams. The use of IVIG or CMV IG, or the adoptive transfer of HCMV-specific T cells, may also be considered in selected cases. Among these immunomodulatory strategies, reduction in immunosuppression is an accepted practice, albeit not standardized, while the use of IVIG and CMV IG remains hotly debated. In contrast, adoptive transfer of HCMV-specific T cells remains investigational, and even though promising data exist in regards to its efficacy, its safety profile needs to be better defined. As novel and investigational antiviral drugs and strategies are being developed, their role for HCMV management will depend not only on demonstrated efficacy but also on safety considerations that will play an equally important role.
Related Knowledge Centers
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- Lymphocyte
- T Cell
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