The field of immunometabolism has attracted growing attention in recent years due to the high potential for the development of cancer immunotherapies. Upon activation, T lymphocytes (T cells) undergo significant metabolic changes that allow them to mediate immune responses. Stimulating these and other immune cells has important outcomes beyond energy production (Fig. 1). A key
Scientists from Boston Children’s Hospital and Massachusetts Institute of Technology (MIT) have used alpaca-derived nanobodies to create a novel approach to CAR T cell therapy that addresses the challenge of treating patients with solid tumor cancers. Currently, CAR-T cell immunotherapy has been applied to the treatment of non-solid tumors such as acute lymphoblastic leukemia (ALL).
Following successful clinical studies, the FDA and regulatory authorities around the world have approved the use of axicabtagene ciloleucel (Yescarta™) for patients with large-B-cell lymphomas and tisagenlecleucel (Kymriah™) for adults with certain types of non-Hodgkin lymphoma. Despite its success as a novel way of treating cancer, physician scientists are realizing that 30%-50% of patients who
Cancer can exploit immune regulatory checkpoints molecules by inhibiting anti-tumor immune responses from T cells. These immune checkpoint inhibitor (ICI) antibodies that activate anti-tumor immune responses can create durable responses in 10%–20% of cancer patients, but the remaining 80%–90% of the patients do not respond, driving the need to find novel combination therapies that increase
T cells expressing chimeric antigen receptors (CAR T) are particularly promising for the treatment of refractory cancers. While Kymriah and Yescarta are FDA-approved for B-cell malignancies, safety and efficacy concerns remain across the cell therapy industry. Severe cytokine release syndrome triggered by T cell infusion is one of the urgent CAR T related downsides that needs
Patients with relapsed or refractory chronic lymphocytic leukemia (CLL) have terrible prognoses and novel cell therapies provide a glimmer of hope. While the CAR T therapy known as Kymriah led to complete remission in over 90% of patients with advanced acute lymphoblastic leukemia (ALL), only 26% of CLL patients responded to it in clinical trials.
In 2017, the FDA approved two immunotherapies based on a patient’s own genetically modified T-cells — Kymriah to treat B-cell acute lymphoblastic leukemia and Yescarta to treat B-cell lymphoma. These therapies rely on chimeric antigen receptor (CAR) T-cells which consist of collecting a patient’s own immune cells, engineering them to target a specific marker, and
Interleukin-2 (IL-2) is a cytokine critical to effector T cell expansion, survival, and function. Importantly, IL-2 is supplemented in the production of T cells for immunotherapy, including CAR-T cell therapies. While IL-2 can improve T cell survival and efficacy, IL-2 provokes a wide range of responses by simultaneously activating and repressing different components of the
It has been known that inhibition of T cell function occurs because of the presence of a complex immunosuppressive microenvironment, which ultimately limits the full potential of T cell therapy. Development of checkpoint inhibitors has been one clinical strategy aimed at curbing such immune suppression, though the full extent of the pathways involved is not yet