CAR T Cell Therapy Flashcards
Bin He, PhD
Associate professor in immunobiology & transplant sciences at methodist research institute
What are the 5 pillars in cancer treatment
-surgery
-chemotherapy
-radiation
-targeted therapy
-immunotherapy
the three FDA approved cancer immunotherapies
-high dose IL-2 therapy
-immune checkpoint inhibitor
-CAR T cell therapy
T Cell
soldiers which fight cancer for us
what is IL-2?
a cytokine cloned as a T cell growth factor - it binds to its receptor to cause proliferation of T cells
What is IL-2 used for
high dosage works as cancer immunotherapy with response rates of 15-20% for metastatic renal carcinoma and metastatic melanoma
What are 3 immune checkpoint inhibitors?
- Ipilimumab - anti-CTLA4
- Opdiv & Keytruda - anti-PD1
- Tecentriq - anti-PD-L1
immune checkpoint inhibitors
antbodies, function to stop the brake, making engine bery powerful
T cell vs CAR T cell
CAR T cell includes chimeric antigen receptor. does not attach to MHC. uses scfv to bind to tumor antigen
Emily Whitehead before treatment
Diagnosed with acute lymphoblastic leukemia, underwent 2 failed rounds of chemotherapy, expected to live a few weeks in hospice
Emily Whitehead experimental treatment
Became first pediatric patient to receive CAR T therapy in April 2012, has been cancer free for 11.5 years
Emily Whitehead adverse events
cytokine release syndrome & neurotoxicity: high fevers, respiratory failure, shock, on ventilator for 2 weeks, IL-6 level elevated 1000x
How many CAR T cell therapies are approved by the FDA?
6: Kymriah, Yescarta, Tescarus, Breyanzi, Abecma, Carvykti
where do cytokines come from
the CAR T cells
solutions for adverse events for CAR T therapy
-cytokine syndrome and neurotoxicity can be handled well
-the risk of losing a patient is very rare
why is prostate caner less responsive to CAR T
it has less mutations, body does not recognize it as foreign?
solutions for high cost of CAR T therapy
-off the shelp allogenic CAR T cells
-in vivo CAR T cells
good target for prostate cancer CAR T cell therapy
cell surface antigen
selectivly expressed in prostate cancer
cannot be sxpressed in vital organs
Prostate Specific Membrane Antigen
-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
Androgen deprivation therapy is used to
increase the amount of PMSA on the cell surface by 5-10 fold
_____% of prostate cancers are PMSA positive
95
strikingly, PMSA is also expressed in blood vessels of other type of solid tumors but not
in normal blood vessels
structure of PMSA
mostly extracellular
PMSA as a therapeutic target
FDA approved Lu-PMSA-617 radioligand therapy for metastatic castration-resistant prostate cancer patients
Systemic lupus erythematosus
sever autoimmune disease, affecting mostly women
-affects kidney, heart, lung, skin requiring lifelong immunosuppression
auto-antibodies
body generates antibodies against itself, (B cells)
scFv - single chain fragment variable
derived from full length antibody and retains antigen-binding affinity and spcificity
autoantibodies againt to nuclear antigens
dsDNA and nuclear antigens
CD20
molecule on cell surface
B cells stemming from naive B cells to become plasma B cells
CAR T cell theray for SLE
-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
results of CAR T for SLE
rapid expansion of CD19 CAR T cells and depletion of B cells in vivo
-no adverse effects like cytokine release syndrome
summary of CAR T
-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
