The Week India - July 29, 2018

COVER STORY

36 THE WEEK · JULY 29, 2018

HEALTH

cancer—give their immune sys-

tem a boost to target cancer cells

or provide memory immunity

against possible cancers.

The second is as an adjuvant

therapy, after established cancer

treatments—surgery, chemo or

radiation therapy. To re-activate

the immune system to target

remnant cancer cells. In this

situation, the implication of the

vaccine would be that you could

start developing the vaccine at

the moment the patient pres-

ents with cancer. At the time of

initiating the cancer treatment,

you would also have the vaccine

available to provide the immune

system with an extra boost to

fi ght the cancer at a time when

the cancer is most vulnerable.

How is this therapy different

from chimeric antigen receptor

(CAR) T-cell therapy?

The fi rst difference is that we

can use our therapy as a true

vaccine by vaccinating some-

one before they have cancer

and boost the immune system in

targeting cancer cells that could

arise in the future.

Secondly, as an adjuvant

therapy—like CAR T-cell ther-

apy—the difference is that we

provide the immune system

with a much larger repertoire

of cancer-related antigens. One

issue with CAR T-cell therapy

has been that, if cancers mutate

to not express the antigen that

the T-cells are targeted towards,

the therapy loses its function. By

providing the immune system

with more than one or two an-

tigens to respond to, we limit the

risk of this immune evasion by

cancer cells.

Some eureka moments during

research that you would like

to share.

Obviously, the fi rst experiment

we performed that showed

strong rejection of breast cancer

cells in the mice receiving the

iPSC+CpG vaccine was very ex-

citing to us.

Another one was the experi-

ment where we transplanted

T-cells from vaccinated mice to

FOR THE STUDY, Dr Joseph

Wu and Nigel Kooreman

used four groups of mice.

One was injected with a

control solution; another

received an immune-boost-

ing substance called adju-

vant; a third group received

injections of iPSCs that were

genetically matched to each

animal; the fourth received

iPSCs plus adjuvant. All the

animals were later implant-

ed with breast cancer cells.

Tumours grew in most

cases. But, they shrunk

in seven of ten mice that

received iPSCs plus adju-

vant. Two mice of that group

completely rejected the

cancer. Similar results were

observed when musine

versions of melanoma and

mesothelioma (a type of

lung cancer) were studied.

No one knows if the

results will be similar in

humans. There is concern

that IPSCs could develop

into tumours. There are also

questions about how long

the immune response, if

any, from vaccination would

last. Would it protect people

from cancer for 20 years, or

would repeat "boosters" be

needed?

This is hardly the first

endeavour to create a cancer

vaccine. But, as Kooreman

explained, the group’s

approach is powerful, as it

would expose the patient’s

immune system to a variety

of cancer-specific epitopes

in one go. “Once activated,

the immune system is on

alert to target cancers as

they develop throughout the

body,” he said.

The next step will be to

test the approach in human

cells in the lab dish. The

aim is to eventually create

personalised vaccines from

an individual's own iPSCs

that could protect against a

range of cancers.

The study and

its potential

tumour-bearing mice that had

not received the vaccine. This

experiment was designed to

show that the immune response

is very specifi c to cancer and we

were therefore excited to see

that the tumour-bearing mice

were able to reject cancer after

receiving the donor T-cells. ◆