Final Program - American Society of Gene & Cell Therapy

Program Schedule, Saturday, May 18, 2013
Scientific Symposium 430
1:45 pm - 3:45 pm
ROOM: BALLROOM B
Clinical Trials
CO-CHAIRS: Donald B. Kohn, MD and Miguel Sena-Esteves, PhD
SPEAKERS
Helen E. Heslop, MD
Immunotherapy with Viral Speciic T Cells
Immunotherapy with antigen-speciic T cells has the potential to reconstitute antiviral activity post transplant without inducing
GVHD and our group has performed a series of clinical studies showing that virus-speciic cytotoxic T lymphocytes (CTLs) can
reconstitute immunity and treat viral reactivation and disease. To extend this approach to EBV-associated lymphoma occurring in
the immunocompetent host expressing Type 2 latency, we have generated CTL lines targeting the subimmunodominant antigens
LMP1 and LMP2 using antigen presenting cells genetically modiied to overexpress either LMP2 alone or LMP1 and LMP2 by
transduction with an Ad5f35 vectors. 27 of 29 high-risk and/or multiply relapsed patients who received LMP-CTL as adjuvant
treatment remain in remission for a median of 2.5 years after CTL while 13 of 21 patients with detectable disease had clinical
responses. In conclusion, immunotherapy with CTL targeting LMP antigens is well tolerated in patients with EBV+ lymphoma and
infused LMP-CTL can accumulate at tumor sites and induce complete and sustained clinical responses.
Roger J. Hajjar, MD
Gene Therapy for Heart Failure
Congestive heart failure remains a progressive disease with a desperate need for innovative therapies to reverse the course of
ventricular dysfunction. One of the key abnormalities in both human and experimental HF is a defect in sarcoplasmic reticulum
(SR) function, which is responsible for abnormal intracellular Ca2+ handling. Deicient SR Ca2+ uptake during relaxation has been
identiied in failing hearts from both humans and animal models and has been associated with a decrease in the activity of the SR
Ca2+-ATPase (SERCA2a). Over the last ten years we have undertaken a program of targeting important calcium cycling proteins
in experimental models of heart by somatic gene transfer. This has led to the completion of a irst-in-man phase 1 clinical trial
of gene therapy for heart failure using adeno-associated vector (AAV) type 1 carrying SERCA2a. The safety proile of AAV gene
therapy along with the positive biological signals obtained from this phase 1 trial has led to the initiation and recent completion of
a phase 2 trial of AAV1.SERCA2a in NYHA class III/IV patients. In the phase 2 trial, gene transfer of SERCA2a was found to be safe
and associated with beneit in clinical outcomes, symptoms, functional status, NT-proBNP and cardiac structure. Furthermore, the
recent successful and safe completion of the CUPID trial along with the start of more recent phase 1 trials usher a new era for gene
therapy for the treatment of heart failure.
Andrew M. Davidoff, MD
AAV-mediated FIX Gene Transfer for Hemophilia B
We are conducting a phase I/II clinical trial of factor IX gene transfer for severe hemophilia B. In the trial we are using a serotype-8
pseudotyped self-complementary adeno-associated virus (scAAV) vector expressing a codon-optimized coagulation factor IX (FIX)
transgene (scAAV2/8-LP1-hFIXco). AAV-mediated FIX activity at 1-6% of normal has been established in all participants with
follow-up now of between 3 months and 3 years following gene transfer.
Saturday, May 18, 2013
C. Frank Bennett, PhD
Antisense Oligonucleotide Therapies for the Treatment of Neurodegenerative Diseases
Antisense oligonucleotides are chemically modiied oligonucleotides that are designed to speciically bind to a targeted RNA
through Watson-Crick base pairing, modulating the function of the RNA. Because antisense oligonucleotides target RNA, rather
than protein, they can be used to target a broader range of therapeutic targets than can be approached with conventional small
molecule or protein based drugs. Neurodegenerative diseases are an attractive area for antisense technology in that there a number
of diseases in which the genetic basis is known and not easily approachable with small molecule drugs.
Scientific Symposium 431
1:45 pm - 3:45 pm
ROOM: 150 ABC
Do Effective Gene Therapies and Regenerative Medicine Affect Dilemmas of Resource
Allocation
CHAIR: TBD
72
Final Program SALT LAKE CITY, UTAH May 15–18, 2013