The Scientist - USA (2020-04)

54 THE SCIENTIST | the-scientist.com

BIO BUSINESS

than normal natural killer cells,” he

says. Huntington and his colleagues are

currently researching these molecular

switches, and mechanisms that might

turn them on or off.

Other groups are interested in

boosting NK cell activation. One recep-

tor in particular, CD16, appears to be

the equivalent of a gas pedal for NK

cells. “It’s expressed on the NK cell

and then once you engage it, it basi-

cally will [trigger] killing by the NK

cell,” says Genentech’s Oh. Plans to

target this receptor with drugs were

the subject of a $96 million deal

between Genentech and biopharma-

ceutical company Affimed in 2018.

Oh notes that Genentech is addition-

ally investigating whether the cancer-

targeting precision of CD16-activated

cells might be enhanced through CAR-

style engineering involving other pro-

tein receptors.

Rezvani and colleagues are also

combining NK cells with CAR tech-

nology. They have been engineer-

ing cord blood–derived NK cells with

a CAR that targets the CD19 anti-

gen—a well-studied molecule charac-

teristic of certain B cell lymphomas.

“We wanted to target CD19-positive

malignancies, because that’s where the

best results have been published with

CAR T cells,” Rezvani says.

To overcome NK cells’ relatively

short half-life and poor proliferation

in the body, the team also introduced a

gene coding for a cell signaling protein,

interleukin-15. This molecule is known

to encourage NK cells to increase in

number and hang around longer than

normal. Lastly, they engineered a safety

mechanism into the NK cell genome: a

so-called suicide switch gene. Already

used in some CAR T cell therapies, the

switch can be activated with a drug in

the event that the cell therapy shows

signs of serious toxicity in patients.

The researchers administered these

triple-engineered NK cells to 11 patients

with relapsed or treatment-resistant

lymphomas or leukemias that were pos-

itive for the CD19 antigen. According to

results published a few months ago, seven

MAKING A KILLER THERAPY

Natural killer (NK) cells can be extracted directly from umbilical cord blood or from the peripheral blood

of a donor  1 , or generated using stem cells from these or other sources  2. Some biotechs are investigating

the use of unmodified NK cells as cancer therapies  3 ; others are genetically engineering cells to carry chi-

meric antigen receptors (CARs) and other modifications  4 to make them more effective at targeting and

killing cancer cells while sparing healthy tissue.

DONOR PATIENT

BLOOD

STEM CELL

TECHNIQUES

NK CELLS CULTURED

AND EXPANDED

« CAR

 1  3

 2  4

EXTRACTED

NK CELLS

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