1. Introducing Apceden™

2. Topics IMMUNITY AND CANCER DENDRITIC CELL BIOLOGY APCEDEN™
Development of Dendritic Cells
Why Dendritic Cells
Mechanism of Action
CLINICAL TRIALS
APCEDEN™
Preparation
Associated Logistics

3. IMMUNITY AND CANCER

4. 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

6. DC can activate Almost all Immune cells
IMMUNOTHERAPY
DC can activate Almost all Immune cells

7. DENDRITIC CELL BIOLOGY

8. Dendritic Cell Therapy in Cancer

9. DEVELOPMENT OF DENDRITIC CELLS
Our cells of Interest

10. There capacity to activate naïve T cells Antigen Presenting cell
WHY DENDRITIC CELLS?
There ability to migrate through tissue and act on tumors
There capacity to activate naïve T cells
Antigen Presenting cell

11. MoA OF DENDRITIC CELLS ASSOCIATED TUMOR KILLING
Tumor Antigen
Expanding T-Cells
Tumor Killing

12. Clinical Trials with Dendritic Cell therapy

13. 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)

14. FEW CLINICAL TRIALS WITH DC
S 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 12 3
NATIONAL CANCER INSTITUTE
Melanoma I 20 4
HOAG MEMORIAL HOSPITAL
PRESBYTERIAN
Metastatic Melanoma 80 5
HERLEV HOSPITAL
DENMARK
Advanced Melanoma 25 6
STANFORD UNIVERSITY
Multiple Myloma

15. 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

16. 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

17. Apceden™

18. 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.

19. Preparation of Apceden™ from Monocytes (1)
Incubate for 4-6 Hrs
Wash with PBS thrice
Adherent cells
Buffy Coat
Incubate for 6 Days
Incubate for 48 Hrs

20. Preparation of Apceden™ from Monocytes (2)
Generation of Immature Dendritic Cells
Isolation of Monocytes from peripheral blood
Lysate Preparation
Isolation of Tumor cells
Loading of Dendritic cells with whole cell Tumor Lysate
Patient
Mature antigen presenting Dendritic Cells
The APCEDENTM is to be administered to the patient intravenously

21. Associated Logistics
NutriprepTM
Registration
8 Days

22. APCEDEN™
Dendritic Cells
Salubrious
Autologous
Target Specific
Safe
Minimal Toxicity