WEBVTT

NOTE duration: "00:04:42.240"


NOTE Confidence: 0.90722656

00:00:04.000 --> 00:00:05.220
CAR T cell therapy

NOTE Confidence: 0.9694824

00:00:05.839 --> 00:00:08.000
is a treatment using your

NOTE Confidence: 0.9694824

00:00:08.000 --> 00:00:09.139
own T cells

NOTE Confidence: 0.9980469

00:00:09.519 --> 00:00:10.660
that have been modified

NOTE Confidence: 0.9963157

00:00:11.360 --> 00:00:12.880
outside your body and put

NOTE Confidence: 0.9963157

00:00:12.880 --> 00:00:14.080
back into you to attack

NOTE Confidence: 0.9963157

00:00:14.080 --> 00:00:15.575
cancer. In order to make

NOTE Confidence: 0.9963157

00:00:15.575 --> 00:00:16.695
any sense of that, I

NOTE Confidence: 0.9963157

00:00:16.695 --> 00:00:17.414
have to talk a little

NOTE Confidence: 0.9963157

00:00:17.414 --> 00:00:18.454
bit about what the immune

NOTE Confidence: 0.9963157

00:00:18.454 --> 00:00:19.994
system is. So

NOTE Confidence: 0.9919782

00:00:20.295 --> 00:00:21.814
the immune system is this

NOTE Confidence: 0.9919782

00:00:21.814 --> 00:00:22.715
large organ

NOTE Confidence: 0.99449575

00:00:23.175 --> 00:00:24.294
in your body made up

NOTE Confidence: 0.99449575

00:00:24.294 --> 00:00:25.255
of a huge number of

NOTE Confidence: 0.99449575

00:00:25.255 --> 00:00:25.755
cells

NOTE Confidence: 0.9972796

00:00:26.055 --> 00:00:27.414
that is used to detect

NOTE Confidence: 0.9972796

00:00:27.414 --> 00:00:28.474
foreign agents.

NOTE Confidence: 0.9612427

00:00:29.250 --> 00:00:30.870
T cells are a subset

NOTE Confidence: 0.9612427

00:00:31.090 --> 00:00:31.990
of our lymphocytes,

NOTE Confidence: 0.9735897

00:00:32.610 --> 00:00:34.930
and lymphocytes are important immune

NOTE Confidence: 0.9735897

00:00:34.930 --> 00:00:36.790
cells. They play an important

NOTE Confidence: 0.9735897

00:00:36.850 --> 00:00:39.010
role in, defending us from

NOTE Confidence: 0.9735897

00:00:39.010 --> 00:00:39.909
viral infections

NOTE Confidence: 0.9929865

00:00:40.370 --> 00:00:41.809
and helping other parts of

NOTE Confidence: 0.9929865

00:00:41.809 --> 00:00:43.010
the immune system to fight

NOTE Confidence: 0.9929865

00:00:43.010 --> 00:00:43.510
infection.

NOTE Confidence: 0.9794108

00:00:44.485 --> 00:00:45.284
One of the things that

NOTE Confidence: 0.9794108

00:00:45.284 --> 00:00:47.364
t cells do is to

NOTE Confidence: 0.9794108

00:00:47.364 --> 00:00:48.504
literally recognize

NOTE Confidence: 0.97191596

00:00:49.045 --> 00:00:50.565
when one of our own

NOTE Confidence: 0.97191596

00:00:50.565 --> 00:00:52.504
cells is infected by something,

NOTE Confidence: 0.97191596

00:00:52.725 --> 00:00:54.085
by what are called receptors

NOTE Confidence: 0.97191596

00:00:54.085 --> 00:00:55.045
on the surface of those

NOTE Confidence: 0.97191596

00:00:55.045 --> 00:00:56.485
t cells, and then attack

NOTE Confidence: 0.97191596

00:00:56.485 --> 00:00:57.684
those cells and actually destroy

NOTE Confidence: 0.97191596

00:00:57.684 --> 00:00:58.184
them.

NOTE Confidence: 0.99886066

00:00:59.100 --> 00:01:00.780
Our cancer cells aren't always

NOTE Confidence: 0.99886066

00:01:00.780 --> 00:01:02.060
that much different from our

NOTE Confidence: 0.99886066

00:01:02.060 --> 00:01:02.960
normal cells.

NOTE Confidence: 0.99790734

00:01:04.220 --> 00:01:05.740
Our immune system is just

NOTE Confidence: 0.99790734

00:01:05.740 --> 00:01:06.640
not recognizing

NOTE Confidence: 0.9469401

00:01:06.940 --> 00:01:08.300
these cancer cells as far

NOTE Confidence: 0.9469401

00:01:08.300 --> 00:01:08.800
enough

NOTE Confidence: 0.9991862

00:01:09.180 --> 00:01:10.319
to attack them.

NOTE Confidence: 0.99609375

00:01:11.100 --> 00:01:12.700
But we often know that

NOTE Confidence: 0.99609375

00:01:12.700 --> 00:01:13.600
cancer cells

NOTE Confidence: 0.9995117

00:01:14.060 --> 00:01:14.834
make certain

NOTE Confidence: 0.9213867

00:01:15.795 --> 00:01:16.295
proteins,

NOTE Confidence: 0.944458

00:01:16.755 --> 00:01:18.455
which are little molecules,

NOTE Confidence: 0.99604493

00:01:18.915 --> 00:01:20.055
that are on their surfaces.

NOTE Confidence: 0.97314453

00:01:20.994 --> 00:01:21.955
So we can take t

NOTE Confidence: 0.97314453

00:01:21.955 --> 00:01:23.174
cells out of the body

NOTE Confidence: 0.94412667

00:01:23.475 --> 00:01:24.915
and we can engineer them

NOTE Confidence: 0.94412667

00:01:24.915 --> 00:01:25.575
to recognize

NOTE Confidence: 0.988351

00:01:25.955 --> 00:01:27.475
the specific molecules on a

NOTE Confidence: 0.988351

00:01:27.475 --> 00:01:28.455
particular cancer.

NOTE Confidence: 0.95033485

00:01:29.160 --> 00:01:30.200
And once a t cell

NOTE Confidence: 0.95033485

00:01:30.200 --> 00:01:31.260
recognizes something,

NOTE Confidence: 0.9921875

00:01:31.640 --> 00:01:32.860
it can destroy it.

NOTE Confidence: 0.94945526

00:01:36.600 --> 00:01:37.480
So how do we do

NOTE Confidence: 0.94945526

00:01:37.480 --> 00:01:38.680
it? As I said, we

NOTE Confidence: 0.94945526

00:01:38.680 --> 00:01:39.800
take the t cells out

NOTE Confidence: 0.94945526

00:01:39.800 --> 00:01:40.760
en masse. We do it

NOTE Confidence: 0.94945526

00:01:40.760 --> 00:01:42.060
by something called phoresis.

NOTE Confidence: 0.9539388

00:01:42.535 --> 00:01:43.834
A process that's

NOTE Confidence: 0.95317197

00:01:44.295 --> 00:01:45.515
a little bit more complicated

NOTE Confidence: 0.95317197

00:01:45.575 --> 00:01:46.855
than a a general blood

NOTE Confidence: 0.95317197

00:01:46.855 --> 00:01:49.335
donation, but outpatient procedure where

NOTE Confidence: 0.95317197

00:01:49.335 --> 00:01:50.854
the lymphocytes are filtered from

NOTE Confidence: 0.95317197

00:01:50.854 --> 00:01:52.055
a bloodstream for a few

NOTE Confidence: 0.95317197

00:01:52.055 --> 00:01:52.555
hours.

NOTE Confidence: 0.9986049

00:01:53.255 --> 00:01:54.455
Those cells are sent to

NOTE Confidence: 0.9986049

00:01:54.455 --> 00:01:55.115
a laboratory

NOTE Confidence: 0.9550781

00:01:55.735 --> 00:01:56.135
where

NOTE Confidence: 0.98479146

00:01:56.810 --> 00:01:57.690
We put a piece of

NOTE Confidence: 0.98479146

00:01:57.690 --> 00:01:59.210
DNA into that cell, and

NOTE Confidence: 0.98479146

00:01:59.210 --> 00:02:00.910
that DNA is a blueprint.

NOTE Confidence: 0.98479146

00:02:00.970 --> 00:02:01.790
It encodes

NOTE Confidence: 0.9728816

00:02:02.330 --> 00:02:03.690
what's called a receptor or

NOTE Confidence: 0.9728816

00:02:03.690 --> 00:02:04.890
a protein, and it's made

NOTE Confidence: 0.9728816

00:02:04.890 --> 00:02:05.870
up of two

NOTE Confidence: 0.9980469

00:02:06.490 --> 00:02:06.990
distinct

NOTE Confidence: 1

00:02:07.450 --> 00:02:07.950
parts.

NOTE Confidence: 0.97998047

00:02:08.490 --> 00:02:09.530
It's got one part that

NOTE Confidence: 0.97998047

00:02:09.530 --> 00:02:10.410
sticks out of the t

NOTE Confidence: 0.97998047

00:02:10.410 --> 00:02:11.885
cell that recognizes

NOTE Confidence: 0.99785155

00:02:12.345 --> 00:02:13.725
the molecule on the cancer

NOTE Confidence: 0.7664388

00:02:14.105 --> 00:02:15.084
and it's connected

NOTE Confidence: 0.9776804

00:02:15.465 --> 00:02:16.665
to a part that sticks

NOTE Confidence: 0.9776804

00:02:16.665 --> 00:02:18.584
into the cell that signals

NOTE Confidence: 0.9776804

00:02:18.584 --> 00:02:19.705
to the T cell to

NOTE Confidence: 0.9776804

00:02:19.705 --> 00:02:20.764
tell it to kill.

NOTE Confidence: 0.9841087

00:02:21.305 --> 00:02:22.185
And we call it a

NOTE Confidence: 0.9841087

00:02:22.185 --> 00:02:23.865
CAR because that stands for

NOTE Confidence: 0.9841087

00:02:23.865 --> 00:02:24.365
chimeric

NOTE Confidence: 0.99902344

00:02:25.145 --> 00:02:25.645
antigen

NOTE Confidence: 0.99658203

00:02:26.105 --> 00:02:26.605
receptor.

NOTE Confidence: 0.97579753

00:02:27.330 --> 00:02:28.610
And then they're expanded in

NOTE Confidence: 0.97579753

00:02:28.610 --> 00:02:29.650
a laboratory, so we have

NOTE Confidence: 0.97579753

00:02:29.650 --> 00:02:30.790
a lot of these cells

NOTE Confidence: 0.999163

00:02:31.090 --> 00:02:32.290
that we can infuse to

NOTE Confidence: 0.999163

00:02:32.290 --> 00:02:32.950
a patient.

NOTE Confidence: 0.9751485

00:02:33.730 --> 00:02:35.250
These CAR T cells, when

NOTE Confidence: 0.9751485

00:02:35.250 --> 00:02:37.250
they work well, will not

NOTE Confidence: 0.9751485

00:02:37.250 --> 00:02:38.610
only go into the body,

NOTE Confidence: 0.9751485

00:02:38.610 --> 00:02:39.889
but they will divide there

NOTE Confidence: 0.9751485

00:02:39.889 --> 00:02:40.935
and they will stick

NOTE Confidence: 0.95166016

00:02:41.495 --> 00:02:42.474
around. And we've

NOTE Confidence: 0.99672854

00:02:43.014 --> 00:02:44.215
seen that many of these

NOTE Confidence: 0.99672854

00:02:44.215 --> 00:02:45.595
patients have actually been cured.

NOTE Confidence: 0.962786

00:02:46.294 --> 00:02:48.555
It takes many, many providers

NOTE Confidence: 0.962786

00:02:48.614 --> 00:02:49.355
and professionals,

NOTE Confidence: 0.9291585

00:02:50.135 --> 00:02:51.655
both clinically and in the

NOTE Confidence: 0.9291585

00:02:51.655 --> 00:02:52.155
laboratory,

NOTE Confidence: 0.9269354

00:02:52.455 --> 00:02:54.135
in our cell processing lab,

NOTE Confidence: 0.9269354

00:02:54.135 --> 00:02:56.510
in our epheresis unit to

NOTE Confidence: 0.9269354

00:02:56.730 --> 00:02:57.230
collaboratively

NOTE Confidence: 1

00:02:57.770 --> 00:02:58.270
orchestrate

NOTE Confidence: 0.97753906

00:02:58.570 --> 00:02:59.310
the treatment,

NOTE Confidence: 0.99690753

00:03:00.410 --> 00:03:01.550
that's this complicated.

NOTE Confidence: 0.99960935

00:03:01.850 --> 00:03:03.310
It's a pretty big undertaking

NOTE Confidence: 0.75

00:03:03.770 --> 00:03:04.169
and,

NOTE Confidence: 0.9254964

00:03:04.570 --> 00:03:06.330
it requires a program, not

NOTE Confidence: 0.9254964

00:03:06.330 --> 00:03:06.830
just

NOTE Confidence: 0.74658203

00:03:07.290 --> 00:03:08.110
a physician,

NOTE Confidence: 0.99938965

00:03:08.970 --> 00:03:10.510
to administer these treatments.

NOTE Confidence: 0.98553467

00:03:17.625 --> 00:03:19.465
The FDA approvals for these

NOTE Confidence: 0.98553467

00:03:19.465 --> 00:03:20.845
cells are for

NOTE Confidence: 0.91611737

00:03:21.145 --> 00:03:22.825
diseases really of the blood

NOTE Confidence: 0.91611737

00:03:22.825 --> 00:03:24.125
system, so hematologic

NOTE Confidence: 0.99853516

00:03:24.585 --> 00:03:25.085
neoplasms.

NOTE Confidence: 0.96936035

00:03:26.180 --> 00:03:27.060
There is a lot of

NOTE Confidence: 0.96936035

00:03:27.060 --> 00:03:28.900
research trying to harness the

NOTE Confidence: 0.96936035

00:03:28.900 --> 00:03:29.799
same technology

NOTE Confidence: 0.99938965

00:03:30.099 --> 00:03:31.560
to fight solid tumors.

NOTE Confidence: 0.99658203

00:03:32.500 --> 00:03:33.400
Solid tumors

NOTE Confidence: 0.91074216

00:03:33.940 --> 00:03:35.720
in general are more advanced

NOTE Confidence: 0.9168294

00:03:36.420 --> 00:03:37.799
than blood tumors,

NOTE Confidence: 0.9800166

00:03:38.145 --> 00:03:39.765
So they're much more mutant.

NOTE Confidence: 0.9800166

00:03:39.985 --> 00:03:41.285
They're much more heterogeneous.

NOTE Confidence: 0.9960693

00:03:42.065 --> 00:03:43.584
And so Yale has a

NOTE Confidence: 0.9960693

00:03:43.584 --> 00:03:45.265
number of scientists who are

NOTE Confidence: 0.9960693

00:03:45.265 --> 00:03:47.185
working on finding the right

NOTE Confidence: 0.9960693

00:03:47.185 --> 00:03:49.045
target in a cancer cell.

NOTE Confidence: 0.99401855

00:03:49.425 --> 00:03:50.944
The targets are proteins usually

NOTE Confidence: 0.99401855

00:03:50.944 --> 00:03:51.825
on the surface of those

NOTE Confidence: 0.99401855

00:03:51.825 --> 00:03:52.725
cancer cells.

NOTE Confidence: 0.99658203

00:03:53.280 --> 00:03:53.780
However,

NOTE Confidence: 0.9819336

00:03:54.160 --> 00:03:55.440
the cancer cells can often

NOTE Confidence: 0.9819336

00:03:55.440 --> 00:03:57.920
lose those targets, making them

NOTE Confidence: 0.9819336

00:03:57.920 --> 00:03:58.660
not susceptible.

NOTE Confidence: 0.99902344

00:03:59.280 --> 00:03:59.780
So

NOTE Confidence: 0.9922038

00:04:00.320 --> 00:04:02.000
people are looking for targets

NOTE Confidence: 0.9922038

00:04:02.000 --> 00:04:03.040
that it's very hard for

NOTE Confidence: 0.9922038

00:04:03.040 --> 00:04:04.340
the cancer cell to lose.

NOTE Confidence: 0.99853516

00:04:05.365 --> 00:04:06.565
We have a very active

NOTE Confidence: 0.99853516

00:04:06.565 --> 00:04:08.025
clinical trial portfolio

NOTE Confidence: 0.9983724

00:04:08.645 --> 00:04:09.865
for solid tumors,

NOTE Confidence: 0.98598635

00:04:10.725 --> 00:04:11.765
for a lot of different

NOTE Confidence: 0.98598635

00:04:11.765 --> 00:04:13.525
kinds of cancers and different

NOTE Confidence: 0.98598635

00:04:13.525 --> 00:04:15.065
types of CAR T cells

NOTE Confidence: 0.98598635

00:04:15.125 --> 00:04:17.065
or other T cell redirection

NOTE Confidence: 0.9980469

00:04:17.525 --> 00:04:18.025
type

NOTE Confidence: 0.9995117

00:04:18.404 --> 00:04:18.904
therapies.

NOTE Confidence: 0.9969308

00:04:20.160 --> 00:04:21.279
It's a whole range of

NOTE Confidence: 0.9969308

00:04:21.279 --> 00:04:22.180
research from

NOTE Confidence: 0.99902344

00:04:22.480 --> 00:04:22.980
developing

NOTE Confidence: 0.94596356

00:04:23.440 --> 00:04:24.339
in a laboratory

NOTE Confidence: 0.9591191

00:04:24.640 --> 00:04:25.680
what is going to work

NOTE Confidence: 0.9591191

00:04:25.680 --> 00:04:27.120
and then eventually putting it

NOTE Confidence: 0.9591191

00:04:27.120 --> 00:04:28.720
into people. And that whole

NOTE Confidence: 0.9591191

00:04:28.720 --> 00:04:30.240
range of research is super

NOTE Confidence: 0.9591191

00:04:30.240 --> 00:04:31.600
important if we're gonna get

NOTE Confidence: 0.9591191

00:04:31.600 --> 00:04:33.060
more therapies like this

NOTE Confidence: 0.98264384

00:04:33.360 --> 00:04:34.814
that could really change the

NOTE Confidence: 0.98264384

00:04:34.814 --> 00:04:35.614
face of how we treat

NOTE Confidence: 0.98264384

00:04:35.614 --> 00:04:36.114
cancer.