Lecture 13 Flashcards
Two Types of Immunity
Innate and Acquired
Two Types of Antigen Presenting Cells
Macrophage and Dendritic cells
Antigen Presenting Cells (APCs)
Capture antigens from foreign bodies and display them on their cell surface. Then they present the antigen to immature T-cells thereby activating the T-cells to attack cells with these foreign antigens
T-Cells
Cytotoxic (Tc): directly destroys antigens
Helper (Th): stimulates T & B Cells
Suppressor (Treg): inhibits T & B Bells
Memory (Tm): remembers antigens for future encounters
Positive Control System on T Cells
Antigen presented by APC binding to T Cell receptor and ligand on surface on APC binding to co-stimulatory receptor on T cell
Negative Control System on T Cells
CD80 on APCs binding to CTLA-4 receptor on T-cells
PDL1 on APCs binding to PD-1 receptor on T- cells
Tumors Response on Negative Control System on T Cells
Tumors express the PDL1 ligand on their surface which binds to PD-1 receptor on T-cells inactivating T-cells
Checkpoint Inhibitor Drugs
Drugs utilized to block negative signals in order to enhance immune responses
Monoclonal antibodies targeting either the CTLA-4 or PD-1 receptors or the PDL1 ligand
Safety Concerns: autoimmune effects (colitis, pneumonitis, liver dysfunction)
Yervoy
Checkpoint inhibitor drug that target the CTLA-4 receptors (anti-CTLA-4)
Keytruda & Opdivo
Checkpoint inhibitor drugs that target the PD-1 receptors (anti-PD-1)
Long Survival Tails
Excited people about the possibility of checkpoint inhibitors and immunotherapy-oncology drugs in general
Adoptive Cell Transfer
Treatment of patients with cell populations that have been expanded ex vivo
Two Types:
Isolation and expansion of tumor infiltrating lymphocytes
CAR T-cells
CAR T-cells
T-cells from patients that are genetically modified by introducing a chimeric antigen receptor (CAR)
How is new CAR made?
Variable region of monoclonal antibody combined with signaling subunits of the TCR
Adverse Effects of CAR-T cells
Severe cytokine release syndrome (cytokine storm) produce high fevers in patients and they spend 7-10 days in critical care unit
Glioblastoma Multiforme (GBM)
Tumor patients have this in the phase 3 trial for the dendritic cell vaccine DCVax-L
Characteristics:
Most common and most lethal primary brain cancer
Highly aggressive and invasive phenotype
Extremely heterogeneous
DCVax Vaccine
Monocytes were removed from patient’s blood, treated with cytokines to mature into dendritic cells and then exposed to a cell lysate made from the patient’s tumor. The vaccine was then given in the arm of the patient.
DCVax Vaccine Stats
Had clinically significant effects: the 5yr survival more than doubles for both newly diagnosed GBM and for recurrent GBM
Safety profile: there were no significant safety concerns
Most promising aspect: the early data from the trial combining DCVax and Keytruda in treating recurrent GBM. The 24 month survival for SOC was 10% for DCVax alone was 20% and for the combination was 60%. Remember that Keytruda alone gave no better results than the standard of care (SOC)
