Adaptimmune Presents MAGE-A4 and MAGE-A10 pre-clinical data at American Association for Cancer Research (AACR) Annual Meeting...
April 16 2018 - 2:00PM
- Preclinical testing raises no safety
concerns for MAGE A4 -- Refined preclinical
testing strategy expected to further mitigate risk of unexpected
off-target toxicity -
Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell
therapy to treat cancer, presented two posters summarizing
preclinical research with its MAGE-A4 and MAGE-A10 SPEAR T-cells at
the annual AACR meeting at McCormick Place in Chicago, Illinois.
The MAGE-A4 poster presented the discovery process and extensive
preclinical validation work performed by Adaptimmune to
characterize the specificity, affinity, and potency of MAGE-A4
SPEAR T-cells. The T-cell receptor (TCR) engineered to target
MAGE-A4 was found to be specific for MAGE-A4 with an appropriate
affinity and avidity, and there were no safety concerns identified
preclinically. Further, the examination of more than 500 non-small
lung cancer (NSCLC) tumor samples stained by MD Anderson Cancer
Center scientists through its strategic collaboration with
Adaptimmune revealed that the MAGE-A4 antigen is expressed in
approximately 51% of squamous cell carcinomas of the lung, 8% of
adenocarcinomas, and in 24% of all NSCLC cases. In addition,
numerous other tumors express MAGE-A4 at variable levels. Details
about the selection and affinity enhancement of MAGE-A10 SPEAR
T‑cells were also presented. The refined methods used to test this
SPEAR T-cell candidate are expected to further mitigate risk of
unexpected off-target toxicities.
“Our proprietary preclinical development and validation program
for our SPEAR T-cells, developed over more than 10 years, enables
us to generate TCRs that have the right level of specificity,
affinity, and overall avidity for cancer cells expressing specific
targets, while minimizing the risk of off-target toxicity,” said
Rafael Amado, Adaptimmune’s Chief Medical Officer. “MAGE-A4 and
MAGE-A10 are in clinical trials in a variety of solid tumors, and
we expect to deliver data on the benefit:risk profile of these
products throughout the second half of 2018.”
Session, date, time, and location (for both
posters):
• Date: Monday, Apr 16, 2018•
Time: 1:00 PM - 5:00 PM (CDT)•
Location: McCormick Place South, Exhibit Hall A,
Poster Section 24
Poster 1 – MAGE-A4
• Title: Affinity-enhanced T-cell receptor
(TCR) for adoptive T-cell therapy targeting MAGE-A4• Poster
Board Number: 21• Permanent Abstract
Number: 2562 • Objectives:
- Determine the frequency of MAGE-A4 expression in non-small cell
lung cancer (NSCLC) to identify patients most likely to benefit
from SPEAR T-cell therapy
- Perform preclinical testing for specificity, potency, and
safety of MAGE-A4 SPEAR T-cells
• Methods:
- MAGE-A4 expression in NSCLC: 534 resected NSCLC cases (stage I
to IV) with clinicopathological information including overall
survival and recurrence were analyzed for MAGE-A4 expression by
immunohistochemistry (IHC)
- Preclinical testing for specificity, potency, and safety of
MAGE-A4 SPEAR T-cells:− Potency/efficacy testing of MAGE-A4 SPEAR
T-cells by antigen driven proliferation, cytokine release, and
cytotoxicity assays− In vitro testing against panels of primary
normal cells from multiple organ systems in 2-D, 3-D, and induced
pluripotent stem cell culture formats to identify
cross-reactivities in more physiologically relevant cultures−
Molecular mapping of the TCR peptide-major histocompatibility
complex (MHC) binding preferences to identify potential
cross-reactive peptides, verification of identified peptides by
loading candidates on antigen-presenting cells, and expression of
source proteins in antigen-presenting cells to confirm lack of
candidate peptide processing and presentation
• Conclusions:
- MAGE-A4 expression was observed in ~24% of all NSCLC cases,
with higher frequency observed in squamous cell carcinoma (SCC)
(51%) versus adenocarcinoma (8%)
- Extensive in vitro preclinical safety assessment and identified
no major safety concerns for MAGE-A4 SPEAR T-cell reactivity
- This MAGE-A4 SPEAR T-cell is being evaluated in a clinical
trial in patients with in bladder, melanoma, head & neck,
ovarian, NSCLC, esophageal, and gastric cancers
Poster 2 – MAGE-A10
• Title: Selection of affinity-enhanced T-cell
receptors for adoptive T-cell therapy targeting MAGE‑A10•
Poster Board Number: 23• Permanent
Abstract Number: 2564 • Objectives:
Generate and systematically test affinity-enhanced TCRs that
recognize an HLA-A*02 restricted epitope from MAGE-A10
cancer/testis antigens• Develop an extensive in vitro testing
strategy to characterize and reduce the risk of TCR
cross-reactivity, including a novel approach for generating peptide
specificity profiles for candidate TCRs – the peptide X-scan•
Methods:
- Twenty-one parental TCRs recognizing the HLA-A*0201-restricted
MAGE-A10 peptide GLYDGMEHL254-262 (MAGE-A10254-262) epitope were
characterized using surface plasmon resonance (SPR)
- Ten parental TCRs were cloned into a lentiviral vector and
transduced into primary human T-cells, and screened for recognition
of natively processed antigen using MAGE-A10–positive and –negative
cell lines and primary cells as targets
- Three parental TCRs selected for affinity enhancement, and the
complementarity-determining regions (CDRs) of their α- and β‑chains
were mutated, and resulting TCRs tested for affinity and
specificity
• Conclusions:
- Adaptimmune developed an affinity-enhanced TCR with high
specificity and potency against cells expressing HLA-A*0201 and the
cancer antigen MAGE-A10− After generating TCR mutants with diverse
germline and CDR loop sequences, the optimal candidate for
preclinical testing was identified by applying a novel
comprehensive specificity screen (X-scan)− Together with other key
developments in preclinical safety and potency assessments, this
strategy is expected to mitigate the risk of unexpected off-target
crossreactivity and resulting clinical toxicities
- The MAGE-A10 SPEAR T-cell that was selected is being evaluated
in clinical trials in NSCLC, and a triple tumor study in bladder,
melanoma, and head & neck cancers
About AdaptimmuneAdaptimmune is a
clinical-stage biopharmaceutical company focused on the development
of novel cancer immunotherapy products. The Company’s unique SPEAR
(Specific Peptide Enhanced Affinity Receptor) T‑cell platform
enables the engineering of T-cells to target and destroy cancer,
including solid tumors. Adaptimmune is currently conducting
clinical trials with SPEAR T-cells targeting MAGE-A4, -A10, and AFP
across several solid tumor indications. GlaxoSmithKline
plc (LSE:GSK) (NYSE:GSK) exercised its option to exclusively
license the right to research, develop, and commercialize
Adaptimmune’s NY-ESO SPEAR T-cell therapy program in September
2017. Transition of this program to GSK is ongoing. The
Company is located in Philadelphia, USA and Oxfordshire, U.K. For
more information, please visit http://www.adaptimmune.com
Forward-Looking StatementsThis release contains
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995 (PSLRA). These
forward-looking statements involve certain risks and uncertainties.
Such risks and uncertainties could cause our actual results to
differ materially from those indicated by such forward-looking
statements, and include, without limitation: the success, cost and
timing of our product development activities and clinical trials
and our ability to successfully advance our TCR therapeutic
candidates through the regulatory and commercialization processes.
For a further description of the risks and uncertainties that could
cause our actual results to differ materially from those expressed
in these forward-looking statements, as well as risks relating to
our business in general, we refer you to our Annual Report filed on
for 10-K with the Securities and Exchange Commission (SEC) on March
15, 2018 and our other SEC filings. The forward-looking statements
contained in this press release speak only as of the date the
statements were made and we do not undertake any obligation to
update such forward‑looking statements to reflect subsequent events
or circumstances.
Adaptimmune Contacts:
Media Relations:Sébastien Desprez – VP,
Communications and Investor RelationsT: +44 1235 430 583M: +44 7718
453 176 Sebastien.Desprez@adaptimmune.com
Investor Relations: Juli P. Miller, Ph.D. –
Director, Investor RelationsT: +1 215 825 9310M: +1 215 460
8920Juli.Miller@adaptimmune.com
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