Presentations Flashcards
what was Emily Whitehead diagnosed with?
aggressive acute lymphoblastic
leukemia
What happens in CAR T cell therapy?
T cells are removed from a patient and modified so that they express CAR receptors specific to the patient’s particular cancer. The T cells, which can then recognize and kill the cancer cells, are reintroduced into the patient.
CAR-T short for …
Chimeric Antigen Receptor T
CAR-T adverse events
Neurotoxicity, Cytokine release syndrome, Macrophage activation syndrome , B cell aplasia
MOA of CAR-T
- Recognition: CAR-T cells are engineered to target specific
cancer cell antigens. - Binding: Upon antigen recognition, CAR-T cells bind to cancer
cells. - Activation: Signaling domains in the CAR activate the CAR-T cell.
- Cytokine Release: Activated CAR-T cells release cytokines,
initiating an immune response. - Direct Killing: CAR-T cells directly kill cancer cells by releasing
cytotoxic substances. - Memory and Persistence: CAR-T cells persist for long-term
immune surveillance. - Tumor Eradication: Cumulative action leads to cancer cell
eradication
CAR-T is limited in …
solid tumors
challenges of CAR-T
- Tumor vasculature: Expresses reduced adhesion molecules, hindering T cell entry into tumors.
- Dense Extracellular Matrix (ECM): Forms a barrier, impeding T cell
mobility. - Heterogeneous Antigen Expression: Tumor cells exhibit varying antigen
expression, affecting the efficacy of CAR-T cells reliant on target-antigen
recognition. - Immunosuppressive Microenvironment:
Examples of how immunosuppressive microenvironment (such as cytokines) can affect CAR-T
- Regulatory T cells (Treg cells): Produce TGFβ, inhibiting T cell
cytotoxicity and promoting Treg cell polarization. - Myeloid suppressive cells (TAMs and MDSCs): Upregulate inhibitory
ligands (e.g., PD-L1) and secrete immunosuppressive cytokines (TGFβ
and IL-10).
Components of CAR
- variable heavy and light regions (antigen recognition)
- spacer & transmembrane domain
- ITAM regions (trigger intracellular signaling pathways) (signal transduction and T cell activation)
Rovelizumab (Leukarest)
Monoclonal antibody directed against CD11/CD18 cell adhesion proteins
Use of Rovelizumab (Leukarest)
treat patients with hemorrhagic shock
Also used in research for:
Multiple sclerosis
Myocardial infarction
Stroke
Cerebral Vasospasm
Head Trauma
Renal Transplantation
Restenosis
Rovelizumab (Leukarest) MOA
inhibits CD40-CD40L pathway
T/F Rovelizumab can be used in transplantation settings
T
Use of Ozanezumab
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
loss of motor control; swallowing/paralysis/breathing