4 research outputs found
Employing Feature Selection Algorithms to Determine the Immune State of a Mouse Model of Rheumatoid Arthritis
The immune response is a dynamic process by which the body determines whether
an antigen is self or nonself. The state of this dynamic process is defined by
the relative balance and population of inflammatory and regulatory actors which
comprise this decision making process. The goal of immunotherapy as applied to,
e.g. Rheumatoid Arthritis (RA), then, is to bias the immune state in favor of
the regulatory actors - thereby shutting down autoimmune pathways in the
response. While there are several known approaches to immunotherapy, the
effectiveness of the therapy will depend on how this intervention alters the
evolution of this state. Unfortunately, this process is determined not only by
the dynamics of the process, but the state of the system at the time of
intervention - a state which is difficult if not impossible to determine prior
to application of the therapy. To identify such states we consider a mouse
model of RA (Collagen-Induced Arthritis (CIA)) immunotherapy; collect high
dimensional data on T cell markers and populations of mice after treatment with
a recently developed immunotherapy for CIA; and use feature selection
algorithms in order to select a lower dimensional subset of this data which can
be used to predict both the full set of T cell markers and populations, along
with the efficacy of immunotherapy treatment
Engineering Metabolism of Chimeric Antigen Receptor (CAR) Cells for Developing Efficient Immunotherapies
Chimeric antigen receptor (CAR) T cell-based therapies have shown tremendous advancement in clinical and pre-clinical studies for the treatment of hematological malignancies, such as the refractory of pre-B cell acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL), and large B cell lymphoma (LBCL). However, CAR T cell therapy for solid tumors has not been successful clinically. Although, some research efforts, such as combining CARs with immune checkpoint inhibitor-based therapy, have been used to expand the application of CAR T cells for the treatment of solid tumors. Importantly, further understanding of the coordination of nutrient and energy supplies needed for CAR T cell expansion and function, especially in the tumor microenvironment (TME), is greatly needed. In addition to CAR T cells, there is great interest in utilizing other types of CAR immune cells, such as CAR NK and CAR macrophages that can infiltrate solid tumors. However, the metabolic competition in the TME between cancer cells and immune cells remains a challenge. Bioengineering technologies, such as metabolic engineering, can make a substantial contribution when developing CAR cells to have an ability to overcome nutrient-paucity in the solid TME. This review introduces technologies that have been used to generate metabolically fit CAR-immune cells as a treatment for hematological malignancies and solid tumors, and briefly discusses the challenges to treat solid tumors with CAR-immune cells
Engineering Metabolism of Chimeric Antigen Receptor (CAR) Cells for Developing Efficient Immunotherapies
Chimeric antigen receptor (CAR) T cell-based therapies have shown tremendous advancement in clinical and pre-clinical studies for the treatment of hematological malignancies, such as the refractory of pre-B cell acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL), and large B cell lymphoma (LBCL). However, CAR T cell therapy for solid tumors has not been successful clinically. Although, some research efforts, such as combining CARs with immune checkpoint inhibitor-based therapy, have been used to expand the application of CAR T cells for the treatment of solid tumors. Importantly, further understanding of the coordination of nutrient and energy supplies needed for CAR T cell expansion and function, especially in the tumor microenvironment (TME), is greatly needed. In addition to CAR T cells, there is great interest in utilizing other types of CAR immune cells, such as CAR NK and CAR macrophages that can infiltrate solid tumors. However, the metabolic competition in the TME between cancer cells and immune cells remains a challenge. Bioengineering technologies, such as metabolic engineering, can make a substantial contribution when developing CAR cells to have an ability to overcome nutrient-paucity in the solid TME. This review introduces technologies that have been used to generate metabolically fit CAR-immune cells as a treatment for hematological malignancies and solid tumors, and briefly discusses the challenges to treat solid tumors with CAR-immune cells