DF2 final

immunotherapy

a treatment that uses a persons own immune system to fight diseases such as cancer

cell-based immunotherapy

also called adoptive cell transfer therapy, utilizes cells of the immune system as a drug

cell-based immunotherapy

which cells are infused into patients to treat cancer

CD34 and HSCs

Stem cells are which

TIL, TCR T cells, CRISPR and cancer vaccines

Stem cell therapies

TIL

TCR T cells

CAR-T

CRSIPR

Cancer vaccines

which are immunotherapies?

TCR T cells

CAR-T

CRISPR

Stem cell therapies

TIL

TCR T cells

CAR-T

CRSIPR

Cancer vaccines

which are gene based?

Stem cell

TIL

Cancer vaccines

Stem cell therapies

TIL

TCR T cells

CAR-T

CRSIPR

Cancer vaccines

which are nongene based?

nucleus

gene therapies deliver all the way through

RNA

what leaves its body once its done its job

cancer vaccines

ex; DC vaccines

educate T cells to better recognize and kill pre existing tumors and example

adoptive immunotherapies

Ex: CAR-T therapy, TCR therapy

activate and enhance T cell numbers and specificity to better kill tumors and example

Ex: CAR-T therapy, TCR therapy

example of adoptive immunotherapies

DC vaccines

ex of cancer vaccines

cell therapies

immunotherapies utilize cells but are not

antibody engagers

increase immune stimulation and overcome immune inhibition

immunomodulating drugs

immunotherapies utilize cells but are not cell therapies are

cytokines

adoptive transfer of cells is often done by

immunosuppresssive immune cells

what promotes cancer

innate

adaptive

Resistance: innate or adaptive

“resistance is not improved by repeated infection”

“resistance is improved by repeated infection”

antibody

innate

soluble factors: innate and adaptive

“antibody”

“lysosome, complement, interferon”

Innate

adaptive

Cells: innate or adaptive

Phagocytes, NK cells

T lymphocytes

IL 10

inhibit t cell growth

VEGF

inhibit cytokine production

CARS

what gives a lot of specificity

PD-L1, B7-H3, GD2

inhibtory tumor-expressed receptors

TIGIT LAG3 and TIM 3

inhibitory T cell expressed recepotrs

chemotherapy

patietns are pre conditioned with to restrain immune response

CD19 GD2 EGFR and ROR1

common antigens found on cancer cells

CD19

most common antigen for CAR-T therapy

CD19

leukemia antigen

GD2

neuroblastoma brain cancer antigen

ROR1

lung cancer

CAR is complete synthetic

TCR is engineered

CAR or TCR which is synthetic vs engineered

cytokines

proteins that support activation maturation and effector functions of immune cells

15%

emily

% patients do not respond to chemotherapy

example

Viruses

most common way of engineering genes into cells

blood disorders

melanoma

90% of fda approved cell therapies are for

and 1 TIL therapy for

CRS

side effect of graft-vs-host disease

IL6

most dangerous/txic

CRS

causes inflammation

IL6 and IL10

most inflammatory cytokines and toxic

CRS

cna cause organ failure

tolcilizumab

most common anti IL6

grade 1 fever not concenring but 2-4 require vasopressor and IL6 antagonist, so potent they try to eliminate evrything

grade 1 -4 CRS grading

tocilizumab

is the most clinically common antibody used to manage IL6

anti IL6

celll therpay CAR-T patients are treated with

half match

haploidentical is

HLA

matching is based on which protein

full match

HLA-matched is

you or sibling can be full match

HLA-match example

lymphodepletion

step before infusion of therapies ****

lymphodepletion

a chemotherapy to prepare body for immunotherapy

eliminates immune system of patients so no chance of rejection

lymphodepletion does what

1 week before

lymphodepeltion given abt

t cells cause do rejection and cause crs

Lymphocytes remove reactive t cells bc **

Cyclophosphadamide and fludarabine(given daily)

most common drugs for lymphodepletion =***

DNA polymerase

fludarabine inhibits ***

Native cell therapies

unmodified immune cells

Cell-based gene therapies

gene modified cells

IL 2, 7, 15

cytokines that activate t cell for killing

T cells

cytokines activtae

T cells

which cells have to be fully matched

blood disorders(hemapoietic progenitor stem ccell transplantation)

most fda approved cell therapies are for ***

CAR-T

the 2nd largest FDA approved group***

blood disorders, CD19

CAR-T is for what and targets what

melanoma

TIL therapy treats

synovial sarcoma

TCR therapy treats

prostate cancer by DC vaccines

cancer vaccines

prostate cancer

provenge

synovial sarcoma

Tecelera

melanoma

Amtagiv-Lifileucel

leukemia blood disorders

Kymirah

ex vivo and autoglous

All FDA approved CAR-Ts are

blood disorders and CD19

all CAR-Ts are for what and target

CAR

extracellular domain is most important on

no, made syntheitcally

are CARs made form patients DNA

CD28, 4-1BB, OX40

co stimulatory domains of CAR

peripheral blood and cord blood

cord blood

CAR-T cells sources form ?

which source has more immune cells

TCR therapy

which theraoy is only one that ises patietns DNA or blood

freeze them, formulated with stabilizer so doesn’t fall apart

when we formulate bag of cell therapy for patients, we need to what***

DMSO very effective

commonly used cryopreservation