CAR T Cell Therapy

Question 1

Bin He, PhD

Answer 1

Associate professor in immunobiology & transplant sciences at methodist research institute

Question 2

What are the 5 pillars in cancer treatment

Answer 2

-surgery
-chemotherapy
-radiation
-targeted therapy
-immunotherapy

Question 3

the three FDA approved cancer immunotherapies

Answer 3

-high dose IL-2 therapy
-immune checkpoint inhibitor
-CAR T cell therapy

Question 4

T Cell

Answer 4

soldiers which fight cancer for us

Question 5

what is IL-2?

Answer 5

a cytokine cloned as a T cell growth factor - it binds to its receptor to cause proliferation of T cells

Question 6

What is IL-2 used for

Answer 6

high dosage works as cancer immunotherapy with response rates of 15-20% for metastatic renal carcinoma and metastatic melanoma

Question 7

What are 3 immune checkpoint inhibitors?

Answer 7

1. Ipilimumab - anti-CTLA4
2. Opdiv & Keytruda - anti-PD1
3. Tecentriq - anti-PD-L1

Question 8

immune checkpoint inhibitors

Answer 8

antbodies, function to stop the brake, making engine bery powerful

Question 9

T cell vs CAR T cell

Answer 9

CAR T cell includes chimeric antigen receptor. does not attach to MHC. uses scfv to bind to tumor antigen

Question 10

Emily Whitehead before treatment

Answer 10

Diagnosed with acute lymphoblastic leukemia, underwent 2 failed rounds of chemotherapy, expected to live a few weeks in hospice

Question 11

Emily Whitehead experimental treatment

Answer 11

Became first pediatric patient to receive CAR T therapy in April 2012, has been cancer free for 11.5 years

Question 12

Emily Whitehead adverse events

Answer 12

cytokine release syndrome & neurotoxicity: high fevers, respiratory failure, shock, on ventilator for 2 weeks, IL-6 level elevated 1000x

Question 13

How many CAR T cell therapies are approved by the FDA?

Answer 13

6: Kymriah, Yescarta, Tescarus, Breyanzi, Abecma, Carvykti

Question 14

where do cytokines come from

Answer 14

the CAR T cells

Question 15

solutions for adverse events for CAR T therapy

Answer 15

-cytokine syndrome and neurotoxicity can be handled well
-the risk of losing a patient is very rare

Question 16

why is prostate caner less responsive to CAR T

Answer 16

it has less mutations, body does not recognize it as foreign?

Question 17

solutions for high cost of CAR T therapy

Answer 17

-off the shelp allogenic CAR T cells
-in vivo CAR T cells

Question 18

good target for prostate cancer CAR T cell therapy

Answer 18

cell surface antigen
selectivly expressed in prostate cancer
cannot be sxpressed in vital organs

Question 19

Prostate Specific Membrane Antigen

Answer 19

-a type 2 TM proteins on the cell surface of prostate cancer cells
-selectively expressed in normal prostate, highly over-expressed in prostate cancer
-its expression is regulated by androgens

Question 20

Androgen deprivation therapy is used to

Answer 20

increase the amount of PMSA on the cell surface by 5-10 fold

Question 21

_____% of prostate cancers are PMSA positive

Answer 21

95

Question 22

strikingly, PMSA is also expressed in blood vessels of other type of solid tumors but not

Answer 22

in normal blood vessels

Question 23

structure of PMSA

Answer 23

mostly extracellular

Question 24

PMSA as a therapeutic target

Answer 24

FDA approved Lu-PMSA-617 radioligand therapy for metastatic castration-resistant prostate cancer patients

Question 25

Systemic lupus erythematosus

Answer 25

sever autoimmune disease, affecting mostly women
-affects kidney, heart, lung, skin requiring lifelong immunosuppression

Question 26

auto-antibodies

Answer 26

body generates antibodies against itself, (B cells)

Question 27

scFv - single chain fragment variable

Answer 27

derived from full length antibody and retains antigen-binding affinity and spcificity

Question 28

autoantibodies againt to nuclear antigens

Answer 28

dsDNA and nuclear antigens

Question 29

CD20

Answer 29

molecule on cell surface
B cells stemming from naive B cells to become plasma B cells

Question 30

CAR T cell theray for SLE

Answer 30

-C20 is not expressed by plasmablasts and long-lived plasma cells
-a deep depletion of CD19+ B cells and plasmablasts in the tissues could trigger an immune reset in SLE

Question 31

results of CAR T for SLE

Answer 31

rapid expansion of CD19 CAR T cells and depletion of B cells in vivo
-no adverse effects like cytokine release syndrome

Question 32

summary of CAR T

Answer 32

-it has cured many patients with hematological cancers, including B cell malignancies and multiple myeloma
-it has significant potential for autoimmune diseases including lupus, with little toxicity
-Dr. He is working on PMSA