ADAPTIMMUNE: Investigators to Present Preliminary Findings for Adaptimmune?s Gene Engineered T Cells in Myeloma at the Annual American Society of Hematology Meeting on Monday 10 December
Abstracts Published in Today’s Issue of the Journal
Blood
(Oxford, UK and Philadelphia, PA) 16 November, 2012. Adaptimmune
announces the publication of dual abstracts in today’s issue
of the Journal Blood, which report preliminary results from an
early phase study using patients’ own T cells that have been
genetically altered to attack multiple myeloma (MM) cells. Lead
investigators for the study will be presenting the data on December
10th at the annual meeting of the American Society of Hematology
(ASH).
The trial was designed as a single arm open label extension study
where patients are given standard of care (autologous stem cell
transplant) in conjunction with modified T cells. The critical step
in this new approach is that the infused T cells have been
genetically engineered to carry receptors that help the T cells
recognize and attack a tumor, while sparing healthy tissue.
Study objectives are to evaluate the safety, bioactivity and
anti-tumor effect of infusion of patients’ own T cells that
have been genetically modified to express a high affinity T cell
receptor (TCR) specific for a type of tumor antigen (protein) known
as a cancer testis antigen (CT antigen). The target CT antigens in
the study are NY-ESO-1 and LAGE-1.
The initial six patient phase is complete and patients have reached
a minimum of six month follow-up for assessment of tumor response
to the treatment. Based on the encouraging preliminary results,
which will be reported at the conference, the study has been
extended to a target enrolment of 26 patients. To date, infusion of
modified T cells have been well tolerated. The data to be reported
at the ASH meeting demonstrates prolonged persistence of modified T
cells, homing of the cells to marrow (the site of tumor), and
suggests anti-tumor activity.
Multiple myeloma is a hematologic cancer localized to the bone
marrow. With standard therapy, long- term response rates are low,
and the median survival for patients with this disease is three to
five years.
The clinical trial focuses on this unmet medical need and includes
patients who have received prior treatment for their myeloma or who
have disease considered to be high risk, and who are eligible for
an autologous stem cell transplant (auto-SCT). Auto-SCT is the
transplant of a patient’s own stem cells, which is a standard
of care for treatment of multiple myeloma in the U.S. Infusion of
the gene modified T cells occurs just following auto SCT.
Presentations at the ASH meeting will be made on Monday, December
10, in non-overlapping sessions.
Dr. Aaron Rapoport, the Chair of the clinical study, will present
abstract 472 entitled “Adoptive Transfer of Gene-Modified
T-Cells Engineered to Express High-Affinity TCRs for Cancer Testis
Antigens (CTAs) NY-ESO-1 or Lage-1, in MM Patients Post
Auto-SCT”.
Dr. Michael Kalos, the lead correlative scientist on the study,
will present abstract 755 entitled “Prolonged T Cell
Persistence, Homing to Marrow and Selective Targeting of Antigen
Positive Tumor in Multiple Myeloma Patients Following Adoptive
Transfer of T Cells Genetically Engineered to Express an
Affinity-Enhanced T Cell Receptor against the Cancer Testis
Antigens.”
In addition, Dr. Carl June, study sponsor and recipient of the 2012
prestigious Ernest Beutler Award for major translational advances,
will present data from the study at the Beutler Lecture, also on
Monday.
“I am very pleased to speak about this promising study at ASH
this year,” says Dr. June. “Adaptimmune’s
technology is an important component of the next generation of
cancer therapies predicated on harnessing the power of the T
cell.”
“From a clinical perspective, I am encouraged by these
preliminary findings which will enable us to continue to evaluate T
cell therapy for myeloma, and I look forward to the opportunity to
present the data for review in a national forum,” says Dr.
Rapoport.
Despite the preliminary nature of the study, we have learned a lot
already from our careful and integrated analyses of blood, marrow
and serum in these patients,” says Dr. Kalos. “This
allows us to correlate the engraftment, cytokine production and
also changes in target tumor antigen over time, and to demonstrate
anti-tumor activity of the infused cells in vivo”.
“We are tremendously pleased with the emerging clinical data
in our myeloma programme,” says Dominic Smethurst, Medical
Director at Adaptimmune. “We are working with a world class
team of investigators, who are very engaged with ensuring the
clinical advancement of this technology.”
Additional study details and contact information for patients
interested in finding out more about participation can be found at
clincialtrials.gov, under trial identifier number
NCT01352286.
Dr. Carl H. June at the University of Pennsylvania (UPenn) Abramson
Cancer Center and Dr. Aaron Rapoport of the University of Maryland
Marlene and Stewart Greenebaum Cancer Center, developed the study.
Dr. June is the regulatory sponsor (FDA representative) for the
study, Dr. Rapoport is the lead clinical investigator at the
University of Maryland and protocol Chair, and Dr. Michael Kalos is
the Director of the Translational and Correlative Sciences
Laboratory at UPenn, and leads the correlative analyses for the
study. Other investigators include Dr. Edward Stadtmauer who is the
lead clinical investigator at the UPenn Abramson Cancer Center, and
Dr. Dan Vogl who is a sub-investigator also at UPenn. Adaptimmune
Ltd is the financial sponsor and owns the core T cell receptor
technology. T cell manufacturing is performed at the Clinical Cell
and Vaccine Production Facility at the University of Pennsylvania
directed by Dr. Bruce Levine.
Ends
Contact
Margaret Henry
PR Consultant
Adaptimmune Ltd, UK
T: +44 (0)1865 261491
E: m.henry@oxin.co.uk
Images available on request:
1. T cell (blue) killing a tumor cell (red)
2. Adaptimmune laboratory – Scientist cloning a T cell
receptor
3. Adaptimmune laboratory – Scientists growing research
cells
4. Adaptimmune laboratory – Scientists growing a cell therapy
product
Notes for editors
About Adaptimmune
Adaptimmune is focused on the use of T cell therapy to treat HIV
and cancer. It aims to utilize the body’s own machinery
– the T lymphocyte cell – to target and destroy
cancerous or infected cells.
Established in July 2008 with a research base in Oxford, UK and
clinical base in Philadelphia, US, Adaptimmune was set up to a
develop unique T cell receptor engineering technology for adoptive
T cell therapy exclusively licensed from Immunocore Ltd (formerly
Avidex/MediGene). Specifically, Adaptimmune makes use of the
body’s ability to recognize infected or cancerous cells by
enhancing the power of the T cell receptor (TCR) on killer T cells.
All cells, including cancerous cells, will typically present small
parts or peptides of internal proteins on their surface as part of
the natural protein processing pathway. This offers a "molecular
fingerprint" of the protein called an epitope for killer T-cells
from the immune system to identify and destroy. However, since
cancer proteins are usually derived from self proteins against
which naturally selected TCRs in the body do not respond, the
Adaptimmune technology uniquely enhances the natural TCR affinity
to these cancer-specific epitopes enabling targeted killing of the
cancer cells.
Adaptimmune has undertaken significant preclinical development with
a number of pipeline TCRs to demonstrate their potency and
specificity in vitro. The TCR in the current myeloma study
specifically recognizes two cancer testis antigen targets: NY-ESO-1
157-165 and LAGE-1 (HLA A2; SLLMWITQC), and was engineered using
Adaptimmune’s proprietary TCR engineering platform. Myeloma
is the lead indication for the therapy, with related trials in
melanoma and sarcoma also recruiting patients and further trials in
ovarian and hepatic cancer scheduled to open in 2013.
http://www.adaptimmune.com
Posted: November 2012
