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Sunday, December 6, 2015
bluebird bio Presents Pre-Clinical and Manufacturing Data from CAR T Oncology Programs at ASH Annual Meeting
ORLANDO, Fla.--(BUSINESS WIRE)--bluebird bio, Inc. Kemadrin (Procyclidine) with free Rx (NASDAQ:BLUE), a clinical-stage company committed to
developing potentially transformative gene therapies for severe genetic
diseases and T cell-based immunotherapies for cancer, announced that
pre-clinical data from its anti-BCMA oncology program were presented by
bluebird bio scientists at the 57th American Society of
Hematology Annual Meeting.
“We believe the unique science and translational gene therapy platforms
we have built differentiate bluebird bio in the oncology field and have
the potential to yield important new therapies for patients living with
cancer. Myambutol (Ethambutol) with free Rx Our three oncology posters at ASH this year, covering critical
basic research, translational and manufacturing aspects of our T cell
oncology pipeline, demonstrate the strength of our T cell immunotherapy
translational science,” said Rob Ross, M.D., head of oncology, bluebird
bio. About Coumadin (Warfarin) with no prescription “We are also excited to see the first anti-BCMA clinical data from
Dr. Intagra with free prescription Jim Kochenderfer of the National Cancer Institute, which was
highlighted in yesterday’s press release from ASH. About Cardura (Doxazosin mesylate) We believe these data
provide excellent proof of concept for bb2121 and are pleased that Jim
will serve as one of the principal investigators for our Phase 1 study
of bb2121.”
Abstract #1893: Manufacturing an Enhanced CAR T Cell Product by
Inhibition of the PI3K/Akt Pathway During T Cell Expansion Results in
Improved In Vivo Efficacy of Anti-BCMA CAR T Cells
Overview and results, presented by Molly Perkins, D.Phil., bluebird bio,
include:
bluebird bio explored the potential for culture modifications to
improve the therapeutic potential of CAR T cells without adding
complexity to manufacturing. Buy Hoodia Diet Pills online The company tested this hypothesis using
CAR T cells specific to B cell maturation antigen (BCMA) manufactured
using standard IL-2 culture with an inhibitor of PI3K added to the
media, or with IL-7 and IL-15, in place of IL-2.
In an in vivo aggressive lymphoma model, mice treated with
anti-BCMA CAR T cells cultured only with IL-2 experienced no effect on
tumor growth and succumbed to the tumors within two weeks after
treatment; anti-BCMA CAR T cells grown in IL-7 and IL-15 also did not
affect tumor growth. http://medical-reviews.blogspot.com In contrast, mice treated with anti-BCMA CAR T
cells cultured with IL-2 and an inhibitor of PI3K experienced complete
and long-term tumor regression.
In an in vivo multiple myeloma model, mice received a single
administration of anti-BCMA CAR T cells cultured under various
conditions; all treatment groups demonstrated tumor regression
regardless of culture conditions. In a model of tumor relapse, two
weeks after tumor clearance, surviving mice were re-challenged with
the same multiple myeloma tumors on the opposite flank; only animals
that had been treated with anti-BCMA CAR T cells cultured with the
PI3K inhibitor were able to resist subsequent tumor challenge.
These data suggest that inhibition of PI3K during ex vivo
expansion may generate a superior anti-BCMA CAR T cell product for
clinical use; this approach could potentially apply to the manufacture
of CAR T cell therapies against other oncology targets.
Abstract #3094: A Novel and Highly Potent CAR T Cell Drug Product for
Treatment of BCMA-Expressing Hematological Malignancies
Overview and results, presented by Alena Chekmasova, Ph.D., bluebird
bio, include:
bluebird bio has developed a CAR targeting BCMA (bb2121) that consists
of an extracellular single chain variable fragment scFv antigen
recognition domain derived from antibodies to BCMA linked to CD137
(4-1BB) co-stimulatory and CD3zeta chain signaling domains.
Based on receptor density quantification, bb2121 can recognize tumor
cells expressing less than 1,000 BCMA molecules per cell.
In a preclinical BCMA+ multiple myeloma xenograft model, a single IV
administration of bb2121 anti-BCMA CAR T cells resulted in rapid and
sustained elimination of the tumors with 100 percent survival, while a
month-long course of anti-myeloma therapy Velcade® (bortezomib)
only delayed tumor growth.
Using flow cytometry and immunohistochemistry, bb2121 T cells were
shown to rapidly target and infiltrate tumors, and T cell expansion
was correlated with tumor regression.
bb2121 anti-BCMA CAR T cells also induced xenograft regression and
enhanced survival in a preclinical model of advanced Burkitt’s
lymphoma.
Taken together, these studies support the potential clinical
application of bb2121 for the treatment of patients with tumors
expressing BCMA.
Abstract #3243: Characterization of Lentiviral Vector Derived
Anti-BCMA CAR T Cells Reveals Key Parameters for Robust Manufacturing of
Cell-Based Gene Therapies for Multiple Myeloma
Overview and results, presented by Graham W.J. Lilley, M.Sc., bluebird
bio, include:
Successful personalized medicine will require robust and reproducible
drug product manufacturing. A series of experiments were conducted to
determine whether variations in anti-BCMA CAR surface expression
resulted in changes in the activity of CAR T cells.
T cells transduced with varying amounts of virus to yield different
amounts of CAR surface expression were diluted with donor-matched
untransduced cells to achieve a uniform population of T cells
containing 26 ± 4 percent anti-BCMA CAR T cells. When exposed to
tumor, these CAR T cell populations exhibited no difference in
cytotoxicity against BCMA-expressing cells.
All T cell productions easily achieved a level of anti-BCMA CAR
expression that resulted in potent anti-BCMA activity, thus potency of
the final drug product was shown to be independent of total anti-BCMA
CAR expression on the cell surface.
These data show that the bluebird bio T cell manufacturing process has
the potential to overcome significant challenges associated with
personalized medicine by reducing the effects of variability while
maintaining potency in autologous cellular drug product manufacturing.
Investor Webcast Information
bluebird bio will host an investor event that will be webcast live at
8:30 p.m. ET today, December 6, 2015, to discuss the ASH data and
provide a brief overview of the science and clinical development plans
surrounding the gene therapy, genome editing and immunotherapy programs.
The live webcast can be accessed under "Calendar of Events" in the
Investors and Media section of the company s website at .bluebirdbio.com.
The webcast will be available for replay for 30 days on the company
website. Alternatively, investors may listen to the call by
dialing (844) 825-4408 from locations in the United States or (315)
625-3227 from outside the United States. Please refer to conference ID
number 71438159.
About bluebird bio, Inc.
With its lentiviral-based gene therapies, T cell immunotherapy expertise
and gene editing capabilities, bluebird bio has built an integrated
product platform with broad potential application to severe genetic
diseases and cancer. bluebird bio’s gene therapy clinical programs
include its Lenti-D™ product candidate, currently in a
Phase 2/3 study, called the Starbeam Study, for the treatment of
childhood cerebral adrenoleukodystrophy, and its LentiGlobin® BB305
product candidate, currently in three clinical studies for the treatment
of beta-thalassemia major and severe sickle cell disease. bluebird bio’s
oncology pipeline is built upon the company’s leadership in lentiviral
gene delivery and T cell engineering, with a focus on developing novel T
cell-based immunotherapies, including chimeric antigen receptor (CAR T)
and T cell receptor (TCR) therapies. bluebird bio’s lead oncology
program, bb2121, is an anti-BCMA CAR T program partnered with Celgene
and focused on hematologic malignancies. bluebird bio also has discovery
research programs utilizing megaTALs/homing endonuclease gene editing
technologies with the potential for use across the company’s pipeline.
bluebird bio has operations in Cambridge, Massachusetts, Seattle,
Washington, and Paris, France.
LentiGlobin and Lenti-D are trademarks of bluebird bio, Inc.
Forward-Looking Statements
This release contains “forward-looking statements” within the meaning
of the Private Securities Litigation Reform Act of 1995, including
statements regarding the clinical potential and manufacturing of the
Company’s anti-BCMA oncology program, including its bb2121 product
candidate. Any forward-looking statements are based on management’s
current expectations of future events and are subject to a number of
risks and uncertainties that could cause actual results to differ
materially and adversely from those set forth in or implied by such
forward-looking statements. These risks and uncertainties include, but
are not limited to, the risk that the preclinical efficacy and
safety data for our bb2121 product candidate will not be observed in our
planned clinical studies, the risk of cessation or delay of any of the
ongoing or planned clinical studies and/or our development of our
product candidates, the risk of a delay in the enrollment of patients in
our clinical studies, the risk that our collaboration with Celgene
Corporation will not continue or will not be successful, and the risk
that any one or more of our product candidates will not be successfully
developed and commercialized. For a discussion of other risks and
uncertainties, and other important factors, any of which could cause our
actual results to differ from those contained in the forward-looking
statements, see the section entitled “Risk Factors” in our most recent
quarterly report on Form 10-Q, as well as discussions of potential
risks, uncertainties, and other important factors in our subsequent
filings with the Securities and Exchange Commission. All information in
this press release is as of the date of the release, and bluebird bio
undertakes no duty to update this information unless required by law.
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