L1: Clinical Considerations for immunotherapy (M. Butler)

Question 1

tree requirements for spontaneous therapeutic immune response

Answer 1

immunization
T-cell response
overcome immune suppression

Question 2

CTLA-4 blockade

Answer 2

ipilimumab
increased T cell activation during priming
increased T cell diversity
inhibition of Treg suppression
lower response rate

Question 3

PD-1 / PD-L1 Blockade

Answer 3

pembrolizumab, nivolumab
reduction of T cell exhaustion/anergy
blockade of direct tumor-mediated T cell inhibition

Question 4

pseudo-progression

Answer 4

immune response criteria for clinical trials has nothing to do with the immune response
Pseudo-progression occurs when there is an initial apparent increase in tumor size or progression of disease on radiographic imaging, despite the patient clinically benefiting from the treatment.

Question 5

immunotherapy

Answer 5

not treating cancer directly
treating the immune system - why there might be a delay in the response (pseudo-progression)

Question 6

RECIST

Answer 6

Response evaluation criteria in solid tumors
goal: to establish the amount of shrinkage that could not be ascribed to operator error and that would not be found if a placebo was administered
goal was not to decide what would be clinically meaningful but rather what could be measured reliably
immune therapy that is reliant on radiological assessments

Question 7

iRECIST

Answer 7

newer criteria

Question 8

immune related adverse event (irAE) mechanisms from immune checkpoint inhibitors for PD-1

Answer 8

more cytotoxicity
hypothyroidism, pneumonitis, myocarditis, arthralgia, autoimmune diabetes

Question 9

immune related adverse event (irAE) mechanisms from immune checkpoint inhibitors for CTLA-4

Answer 9

hypophysitis, rashes, colitis, enteritis

Question 10

time course of appearance of irAE in ipilimubab (CTLA-4)

Answer 10

rash and diarrhea ters u earlier
hypophysitis r şeklinde, continues
liver toxicity lower peak ters u later on

Question 11

colitis

Answer 11

ulcerative and immune checkpoint appear same on endoscopy
ulcerative: increase in IL17+ CD8 T cells
checkpoint colitis: increased expression of IFNgamma T cells

Question 12

CTLA4 Colitis

Answer 12

colon
between 2nd and 3rd dose
diarrhea

Question 13

PDL1 colitis

Answer 13

small intestine/upper GI tract
less predicatble

Question 14

management of irAE

Answer 14

rule out other cause
steroid are first line
anti-TNFalpha

Question 15

Immune checkpoint inhibitor diabetes

Answer 15

rapid loss of islet function, high glucose, ketoacidosis
40% have autoantibodies

Question 16

impact of steroid management on survival

Answer 16

use of steroids impact varies between patients
can help address skin adverse events

Question 17

2 Cell therapies for adoptive T cell therapy

Answer 17

TILs and T cell

Question 18

TILs (tumor infiltrating lymphocytes)

Answer 18

tumor harvested and T cells are expanded by addition of cytokines

Question 19

T cell therapy

Answer 19

take blood, selectively expand cells related to tumor

Question 20

TCR/CAR

Answer 20

CAR T cells are a type of immune cell that has been engineered to recognize and kill cancer cells in a targeted manner

Question 21

Adoptive cell therapy with gene-engineered T cells

Answer 21

isolate lymphocytes from patient’s blood
antitumor TCR/CAR genes
transduction of peripheral T cells
Redirect the T cells toward tomor cells
expand the genetically engineered T cells
infuse back into patient

Question 22

gp100

Answer 22

differentiation TAA (tumor assocaited antigen) melanoma
targeted by Tebentafusp

Question 23

toxicities of CAR therapy

Answer 23

cytokine release syndrome
immune effector cell-associated neurotoxicity syndrome (ICANS) - can be dangerous for brain - seizures
lymphodeptetion
TCR toxicity

Question 24

Cytokine release syndrome symptoms

Answer 24

inflammatory signs and symptoms associated with exponential T cell proliferation:
fevers, cardiovascular disorder, respirartory disorder, neurological issues (confusion, less consciousness), other organ toxicities
some toxicities can lead to death

Question 25

what is the grading system for CRS

Answer 25

ASTCT

Question 26

What is involved in CRS

Answer 26

IL-6, IL-1
monocyte/macrophage lineage and downstream expression of inflammatory cytokines like
IL-6 can result in fever and cardiovascular toxicities
anti-IL-6 receptor antibody can help (Tocilizumab)