Lecture 13

Question 1

Two Types of Immunity

Answer 1

Innate and Acquired

Question 2

Two Types of Antigen Presenting Cells

Answer 2

Macrophage and Dendritic cells

Question 3

Antigen Presenting Cells (APCs)

Answer 3

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

Question 4

T-Cells

Answer 4

Cytotoxic (Tc): directly destroys antigens
Helper (Th): stimulates T & B Cells
Suppressor (Treg): inhibits T & B Bells
Memory (Tm): remembers antigens for future encounters

Question 5

Positive Control System on T Cells

Answer 5

Antigen presented by APC binding to T Cell receptor and ligand on surface on APC binding to co-stimulatory receptor on T cell

Question 6

Negative Control System on T Cells

Answer 6

CD80 on APCs binding to CTLA-4 receptor on T-cells
PDL1 on APCs binding to PD-1 receptor on T- cells

Question 7

Tumors Response on Negative Control System on T Cells

Answer 7

Tumors express the PDL1 ligand on their surface which binds to PD-1 receptor on T-cells inactivating T-cells

Question 8

Checkpoint Inhibitor Drugs

Answer 8

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)

Question 9

Yervoy

Answer 9

Checkpoint inhibitor drug that target the CTLA-4 receptors (anti-CTLA-4)

Question 10

Keytruda & Opdivo

Answer 10

Checkpoint inhibitor drugs that target the PD-1 receptors (anti-PD-1)

Question 11

Long Survival Tails

Answer 11

Excited people about the possibility of checkpoint inhibitors and immunotherapy-oncology drugs in general

Question 12

Adoptive Cell Transfer

Answer 12

Treatment of patients with cell populations that have been expanded ex vivo
Two Types:
Isolation and expansion of tumor infiltrating lymphocytes
CAR T-cells

Question 13

CAR T-cells

Answer 13

T-cells from patients that are genetically modified by introducing a chimeric antigen receptor (CAR)

Question 14

How is new CAR made?

Answer 14

Variable region of monoclonal antibody combined with signaling subunits of the TCR

Question 15

Adverse Effects of CAR-T cells

Answer 15

Severe cytokine release syndrome (cytokine storm) produce high fevers in patients and they spend 7-10 days in critical care unit

Question 16

Glioblastoma Multiforme (GBM)

Answer 16

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

Question 17

DCVax Vaccine

Answer 17

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.

Question 18

DCVax Vaccine Stats

Answer 18

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)