Transcript introduction to dendritic cell therapy

Introducing Apceden™
Topics
• IMMUNITY AND CANCER
• DENDRITIC CELL BIOLOGY
– Development of Dendritic Cells
– Why Dendritic Cells
– Mechanism of Action
• CLINICAL TRIALS
• APCEDEN™
– Preparation
– Associated Logistics
IMMUNITY AND CANCER
IMMUNITY AND CANCER
• Clinical trials with vaccination of ex-vivo generated dendritic cells
(DCs) pulsed with tumor antigens have provided a proof-ofprinciple that therapeutic immunity can be elicited in cancers
• However Clinical benefit has been observed in only a fraction of
cases when measured by regression of tumors in stage IV cancer
• The next generation of DC vaccines are expected to generate large
numbers of high avidity effector CD8+ T cells to overcome
regulatory T cells and the suppressive environment established by
tumors
• Therapeutic vaccination protocols with improved DC vaccines in
combination with chemotherapy is expected to exploit
immunogenic chemotherapy regimens
IMMUNOTHERAPY
DC can
activate
Almost all
Immune cells
DENDRITIC CELL BIOLOGY
Dendritic Cell Therapy in Cancer
DEVELOPMENT OF DENDRITIC CELLS
Our cells of Interest
WHY DENDRITIC CELLS?
There ability to migrate through tissue and act on tumors
There capacity to activate naïve T cells
Antigen Presenting cell
MoA OF DENDRITIC CELLS ASSOCIATED
TUMOR KILLING
Tumor Antigen
Expanding TCells
Tumor
Killing
CLINICAL TRIALS WITH DENDRITIC
CELL THERAPY
Companies conducting Clinical Trials with
Dendritic Cell Therapy
Name of the Company
Country
Immunocellular
Therapeutics
Prima Biomed
California (USA)
Sydney (Australia
Geron and Merix
US
Aastrom Bioscience
Michigan (USA)
Northwest
USA
DCPrime
Amsterdam (Netherland)
Dandrit Biotech
Denmark
Creagene
Korea
Dendreon
Washington (USA)
FEW CLINICAL TRIALS WITH DC
S No. Trials
Country
Type of Cancer
Phase
No. of
Patients
1
BAYLOR RESEARCH
INSTITUTE
USA
Melanoma, neoplasm I & II
Metastasis
30
2
SAMSUNG MEDICAL
CENTER
KOREA
Prostatic cancer
I & II
12
3
NATIONAL CANCER
INSTITUTE
USA
Melanoma
I
20
4
HOAG MEMORIAL
HOSPITAL
PRESBYTERIAN
Metastatic
Melanoma
I & II
80
5
HERLEV HOSPITAL
DENMARK
Advanced Melanoma
I & II
25
6
STANFORD UNIVERSITY
USA
Multiple Myloma
I & II
30
INTERPRETING CLINICAL EFFICACY FOR DC CTs
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Pre-mature dismissal of therapy is not suggested if ORR is not high for such a therapy
Unrealistic to expect efficient immune responses to eliminate the total tumor burden in a
patient with advanced cancer
Analysis of improved survival benefits in randomized studies and long-term follow-up is
suggested
Molecular pathways or chemotherapeutics now considered active based not on only ORR
but improved survival and/or time to disease progression
A phase III study comparing DC Therapy with standard chemotherapy (DTIC) in melanoma
patients showed insignificant ORR in DC arm but post-hoc analysis demonstrated improved
survival and performance status in specific phenotype
Clinical Trials results suggest that DC vaccination therapy needs to be tailored for preidentified cohorts of patients.
Prolonged survival and good quality of life might be considered a therapeutic success
SOME CONCLUSIONS FROM DC CTs
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DCs are the critical decision-making cells in the immune response and an attractive target
for therapeutic manipulation to enhance otherwise insufficient immune responses to tumor
antigens
Complexity of the DC system requires rational manipulation to achieve protective or
therapeutic immunity
Further research needed to analyze the immune responses induced in patients by distinct ex
vivo generated DC subsets activated via different pathways
Progresses made in the knowledge of DC biology as well as effector/regulatory T cell biology
clearly open the avenues for development of considerably improved clinical protocols
Possibility of including therapeutic vaccination of metastatic disease and preventive
vaccination in patients with resected tumors
The ultimate ex vivo-generated therapeutic DC vaccine will be heterogeneous and composed
of several subsets, each of which will target a specific immune effector.
These ex vivo strategies should help to identify the parameters for DC targeting in vivo, which
lead to the next step
APCEDEN™
WHAT IS Apceden™
• Apceden™ is an autologous (self) monocyte derived Dendritic Cell
immunotherapy which nurtures the patient’s own mononuclear cells
against cancer specific cells
• Patients undergo apheresis for collection of blood monocytes. These cells
are cultured and processed for the production of mature dendritic cells
(DC) against the specific tumor cell type, which are harvested on Day 8.
• Each dose of APCEDEN™ consists of dendritic cells (CD 80+, 83+,
86+,CD14-) more than 1 million in 15ml
• 6 doses are given every 2 weeks for first 3 cycles and next 3 cycles are
given every 3 weeks.
Preparation of Apceden™ from Monocytes (1)
Incubate for 4-6 Hrs
Wash with
PBS thrice
Buffy Coat
Adherent cells
Incubate for 6 Days
Incubate for 48 Hrs
Preparation of Apceden™ from Monocytes (2)
Isolation of Monocytes
from peripheral blood
Isolation of Tumor
cells
Generation of Immature
Dendritic Cells
Lysate Preparation
Loading of Dendritic
cells with whole cell
Tumor Lysate
Patient
The APCEDENTM is to be
administered to the patient
intravenously
Mature antigen
presenting Dendritic
Cells
Associated Logistics
NutriprepTM
Registration
8 Days
APCEDEN™
Dendritic Cells
Salubrious
Autologous
Target Specific
Safe
Minimal Toxicity