introducing apceden™. topics immunity and cancer dendritic cell biology – development of...
TRANSCRIPT
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-of-principle 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
Tumor Antigen
Expanding T-Cells
Tumor Killing
MoA OF DENDRITIC CELLS ASSOCIATED TUMOR KILLING
CLINICAL TRIALS WITH DENDRITIC CELL THERAPY
Companies conducting Clinical Trials with Dendritic Cell Therapy
Name of the Company Country
Immunocellular Therapeutics
California (USA)
Prima Biomed 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 DCS No. Trials Country Type of Cancer Phase No. of
Patients
1 BAYLOR RESEARCH INSTITUTE
USA Melanoma, neoplasm Metastasis
I & II 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 • 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 pre-identified cohorts of patients.• Prolonged survival and good quality of life might be considered a therapeutic success
SOME CONCLUSIONS FROM DC CTs• 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.
Buffy Coat
Incubate for 4-6 Hrs
Adherent cells
Incubate for 48 Hrs
Wash with PBS thrice
Incubate for 6 Days
Preparation of Apceden™ from Monocytes (1)
Patient
Isolation of Monocytes from peripheral blood
Generation of Immature Dendritic Cells
Isolation of Tumor cells
Lysate Preparation Loading of Dendritic cells with whole cell
Tumor Lysate
The APCEDENTM is to be administered to the patient
intravenously
Mature antigen presenting Dendritic
Cells
Preparation of Apceden™ from Monocytes (2)
NutriprepTM
Registration
8 Days
Associated Logistics
APCEDEN™