Horizon eBook - 2020 - 18

Engineering the Immune Response For Therapeutic Success

cancer cells in the core of the tumor and in
the tumor microenvironment and establishes
long-term cellular memory against the tumor
by inducing an adaptive immune response.
CYAD-01 is being evaluated in the
THINK study, a Phase I trial of patients with
metastatic colorectal cancer, ovarian cancer,
and pancreatic cancer who did not respond
to other treatments and did not receive
preconditioning therapy. Early findings from
THINK indicated that CYAD-01 was well
tolerated as a standalone therapy and led to
disease stabilization in 29% of the participants.
More recent findings from the THINK
study showed that CYAD-01 had clinical
benefits in patients with relapsed/refractory
acute myeloid leukemia and myelodysplastic
syndrome. In data presented at the American
Society of Hematology (ASH) conference
in December 2019, 8 out of 15 evaluable
patients treated with CYAD-01 demonstrated
antileukemic activity, including 5 out of 8 that
exhibited an objective response.
Another Phase I trial, SHRINK, administered
increasing doses of CYAD-01 together with
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a combination of leucovorin, fluorouracil,
and oxaliplatin (FOLFOX) to colorectal
cancer patients whose liver metastases may
be surgically removed. At the Society for
Immunotherapy of Cancer (SITC) Annual
Meeting in 2019, of nine patients treated in
the SHRINK study, six presented stable disease
and one had a partial response.
A Celyad program in the allogeneic line,
CYAD-101, the first of a family of non-geneedited allogeneic CAR T‑cell clinical programs,
combines CYAD-01 with a T‑cell receptor
(TCR)-inhibiting molecule (TIM), a peptide
that inhibits TCR signaling to decrease or
eliminate the risk of graft-versus-host disease.
In combination with the FOLFOX regimen,
CYAD-101 is currently in a Phase I trial, called
alloSHRINK, for patients with metastatic
colorectal cancer. At SITC, encouraging
antitumor activity was reported from the trial.
Two patients achieved a confirmed partial
response, and five patients achieved stable
disease.
"In the most recent clinical program in
the autologous setting that we just started,

we combined the use of NKG2D cells with
short hairpin RNA (shRNA) to control the
target expression of the T cells," says Gilham.
As part of an exclusive agreement with
Horizon Discovery Group for the use of its
shRNA technology, Celyad started its nextgeneration autologous NKG2D-based CAR
T‑cell candidate, CYAD-02, which in preclinical
models led to persistent antitumor activity.
Gilham specifies two key goals: First,
improve autologous therapies. Second,
develop CAR T‑cell therapies in an allogeneic
and much more straightforward manner. "Our
hope," he stresses, "is to avoid some of the
challenges that are currently facing some of
our colleagues in the cell therapy space."
Making cell therapies
easier, faster, and safer
"We are building regimens that are patientcentric, not product-centric," says Barry J.
Simon, MD, president and chief administrative
officer of NantKwest. The company's cell
therapy strategy uses the proprietary NK-92
cell line together with an IL-15 cytokine and

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Horizon eBook - 2020

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