Introducing Apceden

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Introducing Apceden
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Topics

• IMMUNITY AND CANCER
• DENDRITIC CELL BIOLOGY
• Development of Dendritic Cells
• Why Dendritic Cells
• Mechanism of Action
• CLINICAL TRIALS
• APCEDEN
• Preparation
• Associated Logistics

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IMMUNITY AND CANCER
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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

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IMMUNOTHERAPY
DC can activate Almost all Immune cells
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DENDRITIC CELL BIOLOGY
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Dendritic Cell Therapy in Cancer
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DEVELOPMENT OF DENDRITIC CELLS
Our cells of Interest
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WHY DENDRITIC CELLS?
There ability to migrate through tissue and act
on tumors
There capacity to activate naïve T cells
Antigen Presenting cell
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MoA OF DENDRITIC CELLS ASSOCIATED TUMOR KILLING
Tumor Antigen
Expanding T-Cells
Tumor Killing
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Clinical Trials with Dendritic Cell therapy
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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)
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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 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
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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

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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

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Apceden
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WHAT IS Apceden

• Apceden is an autologous (self) monocyte derived
  Dendritic Cell immunotherapy which nurtures the
  patients 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.

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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
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Preparation of Apceden from Monocytes (2)
Generation of Immature Dendritic Cells
Isolation of Monocytes from peripheral blood
Lysate Preparation
Loading of Dendritic cells with whole cell Tumor
Lysate
Isolation of Tumor cells
Patient
Mature antigen presenting Dendritic Cells
The APCEDENTM is to be administered to the
patient intravenously
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Associated Logistics
NutriprepTM
Registration
8 Days
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APCEDEN
Dendritic Cells
Salubrious
Autologous
Target Specific
Safe
Minimal Toxicity
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