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
Most Amyotrophic lateral sclerosis is
sporadic
Ozanezumab
monoclonal antibody that target NOGO-A protein within CNS
T/F: Ozanezumab blocks NOGO/NOGO receptor and internalization of NOGO
True
ADE of Ozanezumab
back pain, bronchitis, fall, headaches and procedural pain at biopsy site
Use of Atezolizumab (Tecentriq)
For the treatment of urothelial carcinoma and metastatic non-small cell lung cancer.
MOA of Atezolizumab
Blocks PD-L1 to restore antitumor T cell activity
ADE of Atezolizumab
- tiredness
-decreases appetite
-nausea
-cough
-SOB
Lorvotuzumab
Humanized monoclonal antibody designed for targeting CD56 in small cell lung cancer cells
Lorvotuzumab ADE
peripheral neuropathy, diarrhea, neutropenia, & thrombocytopenia