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A DV E RT ISE M E N T F E AT U R E

HIGH THROUGHPUT TECHNOLOGY DRIVESDEVELOPMENTS IN PERSONALIZEDCANCER IMMUNO-THERAPIES
A conversation with MARVIN GEE, Co-Founder and Head of Target Discovery at 3T Biosciences
Developing effective cancer immunotherapies for solid tumors can be extremely challenging, primarily
because they have physical barriers the immune response must overcome. 3T Biosciences identifies
novel targets of T cell receptors for personalized therapy that enable immune responses to penetratesolid tumors and kill cancer cells. Using a high throughput platform with more than 100 billion different
targets, 3T Biosciences quickly and comprehensively identifies novel targets relevant for developing
cell therapies. These novel targets include neoantigen peptides, which are derived from tumor-specificmutations, as well as self-antigens and various other targets that produce effective immune responses.
Marvin Gee, co-Founder of 3T Biosciences, describes how their platform facilitates the development ofsafer, more effective cancer therapies for solid tumors.
What are the current
challenges in developing cancer
immunotherapies?
A lot of the focus now is on how
we tackle some of the more
severe cancer types, like solid
tumors that have difficult biology
to overcome. Compared to bloodcancers, solid tumors have aphysical barrier. In a naturalimmune response, even if you
generate T cells to a solid tumor,
they often won’t penetrate into
the tissue to begin killing thecancer cells.
One of the major challenges
with cell therapies, in whichlive cells are transplanted into
patients to help treat theircancers, is identifying novel
targets on the surface of tumor
cells that can be accessible
for large patient populations.
These targets come in multiple
flavors, including neoantigens,which are peptides derived
from mutations specific totumors, as well as self-antigens,which are overexpressed in thetumor. Our goal is to identify
novel targets of all types thatcan generate strong immune
responses and are sharedacross patient populations.
Another compounding
difficulty is accessing reliablematerials. Because immune
responses are very specific,
it’s important to use highquality peptides so you canfeel confident that the targets
you identify for cell therapies

can elicit an immune response.
We work with GenScript
to synthesize thousands ofhigh-quality peptides, including
neoantigens, for our assays.
How are you addressing thesechallenges?
Most companies and academics
rely on technologies such as
mass spectrometry, which arelimited to a small set of targets.
As a result, it’s very challenging
to capture the entire repertoireof targets on a cancer cell andit’s often unclear whether thosetargets can elicit an immune
response, which is the end goalof therapy. In contrast, we takesamples from patients that are
responding to therapy, so weknow they’re having productive
T cell responses. We developed
a platform that displays morethan 100 billion targets on yeast,
so we can somewhat mimic anatural cell in the body. By using
a high throughput platform, wecan quickly and comprehensively
identify all the potential targets
that a T cell receptor recognizes.
Then we can hone in on
particular targets that would berelevant for developing therapies.

targets. Several years ago,
there was a famous clinical
trial where people engineereda T cell receptor to be morepotent. While doing this, they
inadvertently introduced an off
target cross reactivity where
the receptor recognized anothertarget derived from a heart
protein in the patients. Bothpatients ended up dying ofcardiac failure. Such off-target
reactivities cannot be detectedwith conventional methods.
With our platform, we cancomprehensively predict both T
cell receptor specificity and off
target cross reactivity. Because
neoantigens are only expressedin tumors, cross-reactivity
is limited in those targets.
This information enables us
to engineer more potent andmore specific T cell receptors,
which is a huge advantage froma safety perspective. As withany high potency therapy inoncology, safety is the number
one priority, but also knowingthat information well aheadof going into the clinic cansave patient lives as well as
significant amounts of time andresearch dollars.

Why is it important to identify
all potential targets of a T cell
receptor?
While T cell receptors
can recognize targets very
sensitively and specifically, theycan also recognize multiple

How does this platform help
with therapy development?
We’re in an era of personalized
medicine where targets canbe very specific to a single
patient. A good case study ofthis is with neoantigens. Whentherapies are developed against
neoantigens they become
extremely personalized, but alsosignificantly more expensive
to generate. Whereas, ourfundamental hypothesis is that
we can find shared immune
responses from several patient
populations against the sametarget. This approach allows us todevelop a cell therapy that can bebeneficial for multiple patients.
What’s next?
Our goal is to deliver safe andeffective therapies for patients.
We’ve set up collaborations withacademics and other partners
to get these very precious
samples from patients that
respond to therapy. Being able
to look at these samples andidentify targets opens the door
for developing T cell receptor
therapies to treat not only
these patients, who often havevery debilitating diseases, butalso other patient populations.
Ultimately, I hope we can bein the clinic, helping patients
who, at the moment, have very
limited options for treatment.

A DV E R T I S E R R E TA I N S S O L E R E S P O N S I B I L I T Y FO R CO N T E N T