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On Location Progress in Transplant and Cellular Therapy
Adoptive “Non-Engineered” T-Cell Therapy Shows
Preliminary Efficacy in Lymphomas
Chimeric antigen receptor (CAR) T-cell
therapies engineered to recognize and
destroy CD19 antigens on the surface of
lymphoma cells have revolutionized the
treatment of diffuse large B-cell lymphoma
(DLBCL), but these products require com-
plex manufacturing processes, which
can lead to delays in treatment. To
overcome these challenges, researchers
from Baylor College of Medicine and
Texas Children’s Hospital are exploring
“non-engineered” T-cell therapies that
are easier to manufacture and able to
target multiple antigens.
At the 2019 Transplantation & Cellular
Therapy Meeting of the ASBMT and
CIBMTR, Ann M. Leen, PhD, from
Texas Children’s Hospital, reported that
this approach was safe and led to com-
plete responses (CRs) in most patients
enrolled in a small study.
Unlike CAR T-cell therapies en-
gineered with viral vectors, with this
approach, researchers selectively expand
a patient’s T cells in the laboratory, con-
ferring them with the ability to target
tumor cells, Dr. Leen explained.
She shared results for 33 patients
who had been treated with this therapy:
The other 15 patients received multi-
TAA-specific T cells to treat active disease.
All of these patients had heavily pretreated
disease, the authors noted, and had been
exposed to a median of four lines of prior
therapy (range not provided).
Of this group, five patients had transient
disease stabilization followed by disease
progression and four had ongoing stable dis-
ease, ranging from three to 18 months after
T-cell infusion.
The remaining six patients (3 with HL
and 3 with DLBCL) had achieved CRs,
according to PET assessment, that ranged
from four to 41 months.
“These clinical responses correlated
with the detection of tumor-reactive T cells
in patient peripheral blood post-infusion,
directed against both targeted antigens as
well as nontargeted TAAs … indicating
induction of antigen/epitope spreading,”
the authors reported.
The researchers noted that no
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• 13 with Hodgkin lymphoma (HL)
• 17 with aggressive non-Hodgkin
lymphoma (NHL; including
DLBCL, mantle cell lymphoma,
and T-cell lymphoma)
• 3 with indolent NHL (including
follicular lymphoma and
marginal zone lymphomas)
The investigators used peripheral blood–
derived T cells that were expanded to
target several tumor-associated antigens
(TAAs): PRAME, SSX2, MAGEA4,
NY-ESO-1, and Survivin. Targeting
multiple antigens simultaneously, the
authors noted, overcomes another
challenge associated with CAR T-cell
therapies that target a single antigen: the
heterogeneity of hematologic malig-
nancies and the possibility for tumor
immune evasion.
After the cells were expanded in
the lab, patients were infused with
between 0.5×10 7 and 2×10 7 multiTAA
T cells/m 2 . No participants received
lymphodepleting chemotherapy.
Eighteen patients had disease that
was in remission at the time of T-cell
infusion and received multiTAA-
specific T cells as adjuvant therapy to
prevent relapse; of these, all but two
maintained disease remission. Remis-
sion duration ranged from three to 42
months among responders.
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