Company to webcast investor event,
“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. 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
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
- bluebird bio explored the potential for culture modifications to improve the therapeutic potential of CAR T cells without adding complexity to manufacturing. 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. 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
- 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
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
bluebird bio has operations in
LentiGlobin and Lenti-D are trademarks of bluebird bio, Inc.
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
Source: bluebird bio, Inc.
bluebird bio, Inc.
Manisha Pai, 617-245-2107
Pure Communications, Inc.
Dan Budwick, 973-271-6085