DENDRITIC CELL THERAPY-DRGM 001.pptx.pdf

Dendritic cell therapy

1. DENDRITI
C
CELL
THERAPY
DR. GANESH MOHAN, KMC.

2. ◻What is a dendritic cell?
◻Background
◻Types of dendritic cells
◻How is a dendritic cell detected?
◻What are the functions of dendritic cells?
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3. Dendritic Cell
(DC)
Definition:
A special type of cell that is the sentinel regulator of the immune system, acting as a
professional antigen presenting cell (APC) capable of activating naïve T cells, NK
cells and stimulating the growth and differentiation of B cells.
In fact, a DC to T cell ratio of 1 to 100 sufficed to initiate vigorous and optimal
responses responses.


INITIATE
DIRECT
REGULATE24-Feb-17
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4. Background
Ralph M Steinman (1943-2011), Canadian immunologist, identified dendritic cells in
1973 and later pioneered the therapy to treat his own pancreatic cancer.

He succumbed to the disease two days before the Nobel award was announced, but
remains a laureate in Physiology/Medicine because the Nobel committee was unaware
of his death.
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5. Why the word dendritic?
•The word ‘dendritic’ means
‘branched like a tree’.

•Greek word ‘dendron’ which means
‘tree’.
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6. Dendritic cells are found in
◻Skin (Langerhan’s cells)
◻Nervous tissue (glial cells)
◻Lymph nodes
◻Spleen
◻Intestines
◻Liver (kupffer’s cells)
◻Bone (osteoclasts)
◻Thymus
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7. DC
Langerhans cells
A B
GFE
Heart DC Kidney DC
Murine Tracheal DC Rat Tracheal DC Human Bronchiole DC
Blood DC
Dendritic cells (DC) are present in the blood
and in the majority of peripheral tissues
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9. Types Of
Dendritic Cells
DC
Myeloid
Monocyte
derived
Langerha
ns
Lymphoi
d
Plasmacyt
oid
CD11c pos
CD 123 neg
HLA DR-pos
Langerin neg
CD11c pos
CD 123 neg
HLA DR-pos
Langerin pos
CD11c neg
CD 123 pos
HLA DR-pos
Langerin neg 24-Feb-17
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10. Subsets Of DC
Population
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11. ◻Myeloid lineage DCs ??????“conventional” DC
◻Monocytes can be driven to become DCs in the
presence of GM-CSF and TNFα ± IL-4
◻Mature myeloid DCs in tissues is known as interstitial
DC and Follicular DC in lymphoid follicles.
◻Interstitial DCs - Activate naïve CD4 and CD8 T
cells and induce differentiation of naïve B cells to
plasma cells (Ab).

Myeloid lineage
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12. ◻Langerhans cells - CD34+, CD 14- & TGF β+. They
activate only naïve T cells, not B cells.
◻Myeloid DCs are usually present in the marginal
zones where pathogen exposure is more.
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13. The Lymphoid DCs
◻The DC subset that originates from CD34+ cells
committed to the lymphoid lineage
◻CD11c- and are driven to become DCs by IL-3.
◻Referred to as Plasmacytoid DCs
◻Have the capacity to produce IFN-α in response to
viral infection and reside in the T cell compartment
of lymphoid tissues.
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14. DC1 DC2
Effect on T cells Th1 Th2
TLRs 2,3,4 & 7 7 & 9
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15. Immature dendritic cell

Mature dendritic cell

▪Principal function Antigen capture Antigen presentation to T cells
▪Exprssion of Fc receptors,
mannose receptors
++ -
▪Expression of molecules
involved in T cell activation:
B7,ICAM-1,IL-12
Absent Or low ++
▪Class II MHC molecules Half life ~ 10 hr Half life~ >100 hr
No.of surface molecules
~1*10
6
No.of surface molecules ~ 7 *
10
6

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16. ◻Immature DCs are characterized by a high ability of
endocytosis and expression of relatively low levels of surface
MHC and co-stimulatory molecules.
◻Thus they are very efficient in antigen uptake but less
efficient in T cell stimulation.
◻Most immature DCs possess three mechanisms to take up
antigen:
Macropinocytosis,
Phagocytosis,
Clathrin-mediated endocytosis
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17. 24-Feb-17
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18. Function of immature dendritic cells
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19. Function of mature dendritic cells
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20. 24-Feb-17
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21. Co-stimulatory
molecules
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22. Why dendritic cells are the most efficient
antigen presenting cells
◻DCs are strategically located at the common sites of entry of
microbes and foreign antigens (in epithelia) and in tissues that
may be colonized by microbes
◻DCs express receptors that enable them to capture microbes
and to respond to microbes
◻These cells migrate from epithelia and tissue preferentially to
the T cell zones of lymph node, through which naïve T
lymphocytes circulate, searching for foreign antigens
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23. ◻Mature DCs express high levels of peptide-MHC
complexes, costimulators and cytokines, all of which
are needed to activate naïve T lymphocytes
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24. Bone Marrow Lymph node
Lymphatics
PAMPs and other
noxious stimuli
Stem cell
CD34
+
Dendritic Cells-Center of the “Immuniverse”
Skin
Epidermis
Dermis
N
K B
Sampling of the environnment 3
CD4
C
D
8
Dermal DC
Langerhans cells

Dendritic cell progenitor
production in the bone
marrow

1
2 Migration to
peripheral tissue
4 Migration
Antigen processing
Antibodies
5
Induction of an
immune response
DC
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26. Dendritic Cell Therapy in Cancer
Recently (2010) approved by the US FDA
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27. Dendritic Cell Therapy
1.Introduction
2.Principle of DC therapy
3.Antigen Presentation and Induction of Cellular Immune Responses
4.Source of Antigen
5.DC Source and Subsets
6.Maturational State
7.Maturation Stimuli
8.Migration
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28. 9.Route, Dose, and Schedule of DC Vaccination
10.Monitoring: clinical markers/surrogate markers
11.DC Vaccination in Infectious Diseases
12.Quality Control
13.Immune Monitoring
14.Clinical Studies in Cancer Patients
15.Conclusion
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29. ◻ Evidence from mouse models
-Immune-compromised mice have increased incidence
of cancers
-Immunisation induces tumour-specific immunity &
reduces tumour mass/tumour growth





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30. ◻Clinical observations
-Spontaneous regressions in immuno-competent
patients
-Immunodeficiency increases some cancers
-Immune infiltrates –better prognosis
-Tumour specific T cells can be isolated
Why Immunotherapy?
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31. Dendritic Cell Immunotherapy
◻There is a great deal of interest in how DCs might be
exploited as a form of immunotherapy
◻DCs are being studied as adjuvants for vaccines or as
a direct therapy to induce immunity against cancer
◻DCs may prove useful in cancer has been most often
studied in animal models
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32. 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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33. 24-Feb-17
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34. IMMUNOTHERAPY
DC can
activa
te
Almos
t all
Immun
e
cells
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36. Immune induction/effector pathways
Modified from Banchereau et al., Ann Rev Immunol. 2000
constitutive trafficking
of dendritic cells
NAÏVE T CELLS
Priming and recirculation
of effector T cells
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37. Tumor Antigen
Expanding
T-Cells
Tumor
Killing
MOA Of Dendritic Cells Associated Tumor Killing
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40. 24-Feb-17
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41. Antigen Presentation and Induction of Cellular Immune
Responses
1. CD8+ T Cells
◻DCs are able to present peptides derived from
exogenous antigens to CD8+ T cells, a phenomenon
referred to as
‘cross-presentation’
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42. 2. CD4+ T Cells
◻ DCs efficiently take up exogenous antigens and
present them to CD4+ T cells as peptides bound in
the groove of MHC class II molecules
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43. ◻Most DCs in peripheral tissues in situ are of the
immature phenotype, the prototype being Langerhans
cells in the epidermis.
◻On maturation DCs downregulate their
endocytic/phagocytic activity and upregulate the
expression of MHC, adhesion, and co-stimulatory
molecules, making them extremely effective in T cell
stimulation
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44. 3. NK Cells

◻The additional activation of NK cells by DC-based immunotherapy
could be valuable for the induction of antitumor immunity. In mice,
DCs directly activate NK cells, which elicit antitumor effects
(FERNANDEZ et al. 1999).
◻Human DCs stimulate resting NK cells, a process that mainly
involves the NKp30 natural cytotoxicity receptor (FERLAZZO
etal. 2002)
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45. 4. NKT Cells

◻Unique subpopulation of T cells building a link between innate
and adaptive immunity
◻A synthetic glycolipid, -galactosylceramide ( -GalCer), binds to
CD1d and efficiently activates NKT cells (KAWANO et al.
1997)
◻DCs pulsed with -GalCer efficiently induce antitumor activity in
mice (TOURA et al. 1999) Therefore, vaccination with
-GalCer-pulsed DCs may be a potential way to induce NKT cells
with antitumor activity in patients.
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46. Source of Antigen
Defined Undefined
Peptides Tumor cells
Proteins Tumor cell lysate
cDNA HSP
Viral vectors mRNA
Undefined Ag
are more potent
but also causes
autoimmunity
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47. 1. Peptides
◻HLA class I molecules (CD8+CTL).
◻Recently several CD4+ helper T cell epitopes have been added.
◻Readily synthesized at GMP quality and used to load onto ex
vivo-generated DCs.
◻Vaccination with peptide-pulsed DCs has been shown to induce
both peptide-specific CD8+ and CD4+ T cells in healthy volunteers
and even in advanced cancer patients (Dhodapkar et al. 1999, 2000;
Schuler- Thurner et al. 2002)
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48. The peptide-based approach has some major
drawbacks
◻The choice of peptides is restricted to the HLA typing of the
patient, at least for HLA class I peptides, which are less
promiscuous binders than HLA class II peptides
◻Vaccination with peptide-pulsed DCs should only induce a T cell
response directed against a limited number of tumor antigens,
which may not be sufficient to effectively combat the tumor
◻Repetitive vaccinations using relatively high peptide
concentrations may favor the induction of low-affinity T cells that
are not able to recognize the tumor cells
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49. 2. Exosomes


◻Exosomes may present an attractive source to load DCs with
antigen
◻They contain adhesion and costimulatory molecules, MHC
products, and heat shock proteins and are secreted by various
cell types including dendritic and tumor cells (WOLFERS et
al. 2001; ZITVOGEL et al. 1999)
◻Exosomes derived from peptide-pulsed DCs induce antitumor
immune responses in mice (ZITVOGEL et al. 1998)24-Feb-17
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50. 3. Dead or Dying Tumor Cells
◻whole antigenic spectrum of a given tumor.
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51. 4. Recombinant Viruses
◻DCs can be readily infected with recombinant viruses
containing the cDNA coding for a given tumor
antigen.
◻With the use of adenoviral or influenza viral vectors
transduction rates of more than 90% can be achieved
(Jenne et al. 2001)
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52. 5. DNA / RNA Transfection
◻Circumvent the disadvantages associated with the use
of viral vectors.
◻DNA coding for full-length tumor antigens.
◻Electroporation.
◻Transfected DCs present the relevant antigens to
human T cells in vitro (Smith et al. 2001, Ashley et al
1997, Koido et al 2000)
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53. 7. Cell Hybrids
◻Fuse tumor cells and DCs with high electric voltage
or polyethylene glycol
◻ Vaccination with the resulting cell hybrids has
been shown to induce regressions of established
carcinomas, lymphomas, and melanomas in mice
(KOIDO et al. 2000; GONG et al. 2000)
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54. 8. In Vivo Targeting of DCs
◻This may be achieved by targeting resident DCs in vivo.
◻Modern vaccination strategies using, for example, naked
DNA (TANG et al. 1992) may prove advantageous
◻DC poietins (e.g., GM-CSF, FLT3-L) may further augment
vaccination efficacy by increasing the number of resident
DCs, which can be activated in vivo by adjuvants such as
IFN-α (LE BON et al. 2000) or CpG oligonucleotides
(JAKOB et al. 1999).
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55. Source Of Antigen
in vitro
in vivo
peptide pulsing
(e.g. synthetic peptides,
acid eluted)
whole-antigen pulsing
(e.g. tumour lysate,
recombinant protein)
genetic-targeting
(e.g. RNA, DNA)
genetic-targeting
(e.g. gene gun, gene therapy)
antibody-antigen
conjugates
(e.g. targeting endocytic receptors)
receptor-mediated
uptake
(e.g. mannosylated antigens)
MHC I
MHC II
helper epitopes
boost CTL priming
maturation signal
provided along with
antigen
maturation signal
provided after
antigen
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56. Plasticity of monocyte-derived dendritic cells
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57. PROCURING DCs
Isolation
Leukapheresis
Generation
CD 34 cells
Monocyte
derived
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58. Isolation of DC
0.15-0.7% of peripheral blood.
When cell selection is combined with leukapheresis – yield is
1-10*10
6
.
Mobilization regimes help to increase the yield.
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59. Dendritric Cell Generation
◻DCs can be generated by culturing CD34+ cells in
the presence of various cytokines.
◻CD34+ cells cultured in the presence of SCF,
Flt3L, IL3 and IL6 (Fong & Engleman).
◻10-30 fold rise in the yield with Flt3L.
◻Differentiated with - GM-CSF and IL-4 ± TNF-α.
◻Hepatocyte growth factor (HGF)
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60. ◻Another approach is to generate DC-like cells by
culturing CD14+ monocyte-enriched PBMC.
◻Differentiated with - GM-CSF and IL-4.
◻These DCs need additional conditioning in vitro
with either TNF-α or monocyte-conditioned media
(MCM) to be able to fully function as a DC.
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61. Cella et al: Origin maturation and antigen
presenting fun of Den. cells
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62. Culture condition
◻Initially cultured with fetal calf serum (FCS).
◻Type 1 hypersensitivity.
◻Now serum free medias (X-VIVO 15 or AIM V)
◻or AUTOLOGOUS serum
◻But, serum from cancer pts have inhibitory IL-10 &
VEGF.
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63. Maturational State
◻Mature DCs are more immunogenic than immature
DCs IN mice (Schuurhuis et al. 2000: Labeur et al.
1999; Inaba et al. 2000).
◻Matured DC - Better clinical response
◻Immature DCs mainly function as antigen-capturing
cells, whereas mature DCs mainly function as
antigen-presenting cells.

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64. Maturation Stimuli
◻Stimuli includes ?????? CD40L, TNFα, PGE2, IL-6, IL-1β and
IFN γ
◻A cocktail of proinflammatory cytokines and prostaglandins
("MCM-mimic") was introduced (Jonuleit et al.1997) and
subsequently applied in many clinical trials.
◻Most widely used cocktail – IL 1β, PGE 2 and TNFα.
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65. Cella et al: Origin maturation and antigen
presenting fun of Den. cells
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66. Generation of DC for vaccine use
◻In-vitro conversion of monocytes
GM-CSF/IL-4 +
maturation cocktail (IL-6, IL-1b,TNF-a, PGE
2
)

◻Expansion from blood CD34
+
stem cells
GM-CSF/TNF-a
TNF-a matures DC
labour intensive, expensive, QC issues

◻ Harvest from blood
with / without growth factor-induced mobilisation
maturation procedure
limited cell number obtained
DC are generated from
each individual

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67. Migration
◻To induce strong T cell responses, it is crucial that a
significant number of antigen-bearing DCs reach the
draining lymph node and remain viable to efficiently
activate T cells.
◻Migration properties and longevity of the injected DCs
play an important role.
◻DC migration is regulated by their response to
chemokines, which is influenced by their maturation
status.
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68. Route, Dose, and Schedule of DC Vaccination
◻1-200*10
6
cells/vaccine.
◻Multiple doses at 2-4 weeks interval.
◻Routes –
Intradermal – easiest approach
Intranodal
Intra tumoral
Intravenous – antigen specific antibody response
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69. Schedule Of DC Vaccinations
◻High dose regimen usually preferred.
◻Repetitive vaccinations can also cause killing of
antigen-loaded DCs by antigen-specific CTLs that
may diminish the immune response (HERMANS et
al. 2000)
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70. Administration / Migration of
DC vaccines
111
Indium labelled DC.
Radionucleotide scintigraphy
(FDA approved).
MRI – with supra
paramagnetic iron oxide.
Not approved, but better
imaging results.
Mature DCs migrate better than
immature DCs.
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71. Clinical Studies in Cancer Patients
◻Melanoma
◻The first human tumor-associated antigen was identified in
melanoma (VAN DER BRUGGEN et al.1991), and currently this
is the best-studied malignancy in the context of DC-therapy.
◻The pioneering work with peptide-loaded, monocyte-derived DCs
(moDCs) has proven the concept of DC vaccination to elicit
tumor-specific CTL responses even in advanced cancer patients
(SCHULER-THURNER et al.2000; THURNER et al. 1999a).
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72. 12.Rosenberg, S. A., Yang, J. C. & Restifo, N. P.
Cancer immunotherapy: moving beyond current
vaccines.
Nature Med. 10, 909–915 (2004
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73. Head And Neck Malignancies
◻pDCs have been located in head and neck cancer,
Tumor-infiltrating pDCs have a diminished capacity to
produce IFN-α in response to stimuli like CpG ODN,
suggesting either that they are matured or that their functions
are impaired.
◻Direct injection of CpG ODN into tumors reduces tumor size
and, when coadministered with mDCs, cures
chemotherapy-resistant tumors(Lonsdorf et al;J.Immun; 2006)
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74. Solid Tumors
◻In contrast to melanoma, many solid tumors are
considered less immunogenic and only few TAAs
have been identified for these tumors.
◻ Clinical studies have been performed with DCs
loaded with peptides as well as with crude tumor
extracts or tumor-derived RNA.
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75. Virus-Associated Malignancies
◻The targets for immune intervention strategies in
these malignancies are different viral antigens.
◻Because they are foreign to the immune system, the
challenge is to circumvent viral immune escape
mechanisms rather than induce autoimmunity
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76. Other Malignancies
◻Because of the immune-privileged status of the central
nervous system (CNS) it is questionable as to whether
DC-based immunotherapy can be applied to patients
with these tumors.
◻ In fact, in a recent study, patients suffering from
malignant glioblastoma or astroglioma were vaccinated
with immature moDCs pulsed with peptides eluted
from autologous tumor cells (YU et al. 2001).
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77. Hematological Malignancies
◻Myeloma and B cell lymphoma respond initially to
standard chemotherapy, but are ultimately incurable.
◻For both tumors, idiotypic proteins have been used as
specific antigens.
◻ B cell lymphoma was the first human malignancy to be
targeted by a DC-based vaccination (HSU et al. 1996)
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78. ◻In myeloma, idiotype- and Id-KLH-pulsed DCs were
used to vaccinate patients after high-dose chemotherapy
and stem cell transplantation (REICHARDT et al. 1999;
LISO et al. 2000; LIM et al. 1999)
◻Although the majority of these patients developed
potent KLH-responses, only minor immune responses
against the tumor antigens or clinical remissions could
be observed.
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79. DC Vaccination in Infectious Diseases
◻The prevention of infectious diseases through
vaccination represents one of medicine’s greatest
triumphs
◻Augmentation of the immune responses by ex
vivo-generated DCs is therefore an attractive
consideration. However, successful DC vaccination
trials have not been reported so far.
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80. ◻Induction of antiparasitic CTLs has been demonstrated
in vitro with DCs loaded with helminthic proteins
(Jenne et al. 2001), and protective immunity against
bacteria has been achieved by DC vaccination in mice
(Worgall et al. 2001).
◻Protection against pulmonary infection with
Pseudomonas aeruginosa after immunization with P.
aeruginosa-pulsed dendritic cells has also been
demonstrated (Mbow et al. 1997).
◻ One of the best-studied animal models in this regard is
leishmaniasis (Moll et al. 2001).
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81. Monitoring outcome
no vaccinevaccine
ELISpot assay
Enzyme-linked immunosorbent spot
MHC-peptide tetramer
Surrogate markers
ICCS
Intracellular cytokine staining
Clinical markers
Disease burden
Clinical signs
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82. Monitoring Clinical Outcome
ON ENTRY
4 MONTHS
Pelvis Chest
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83. ❑Dendritic cell-tumor cell hybrids enhance the
induction of cytotoxic T lymphocytes against murine
colon cancer: a comparative analysis of antigen
loading methods for the vaccination of
immunotherapeutic dendritic cells.

Results suggest that DC-tumor cell fusion hybrids are
more potent inducers of protection against solid
tumors, such as colon cancer, than other
antigen-loading strategies using whole tumor cell
materials.
Yasuda et al


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84. ❑ Dendritic cells in cancer vaccines.

These preliminary trials indicate that
immunotherapies utilizing DC-presenting
tumor-associated antigens can safely be administered
to patients with cancer and induce significant
immunologic and clinical responses.
: Bossart et al
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85. Recent Publications Of Dendritic Cell Therapy

❑Paper entitled 'Managing of Solid Tumors & Prevention of
Metastasis or Revisiting of Cancer by Dendritic based Cancer
Immunotherapy' presented at the National Seminar on Management
of Cancer by Indian Society of Health Administrators, at Bangalore
on September 23, 2012.
In the News: 'The Week' Magazine has reported success of Dendritic
cell therapy.
This paper illustrates five cancer cases, who having received
DENVAX (Dendritic Cell Therapy), have been completely free from
the disease

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86. ❑Presentation in'CANCER IMMUNOLOGY AND
IMMUNOTHERAPY' conference held in NIH, Bethseda, MD
in September 2011

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87. Benefits of Dendritic Cell Therapy:
◻Quality of life improves. In extreme cases, patients facing
cancer recurrence within 3 months can live longer by up
to 9 months.
◻Survival period is likely to be a disease free state.
◻Progression of disease is retarded.

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88. •No side effects because it is not a product manufactured
externally. Graft versus host reaction is absent.
• Prevents side effects such as vomiting and hair loss.
Chemotherapy reduces the cells and frequent chemotherapy is
tiresome because it kills cancer cells and normal cells. Then
the cells have to recuperate.
• Pain free butterfly infusion.
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89. Dendritic Cells
Autologous
Safe
Minimal Toxicity
Target Specific
Salubrious
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90. Role Of A Transfusion Medicine Specialist
◻Immunotherapy directed against cancer or viral
infections may engage Transfusion Medicine
professionals in the harvest and manipulation of
dendritic cells or other immune cells directed against
unwanted pathogens
◻Exploration of the plasticity of the stem cells and
capacity for cellular regeneration may open new fields
of tissue repair and regeneration
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91. ◻The isolation and preparation clinical grade of
dendritic cells have been driven by Transfusion
Medicine Specialists who are well versed in the
similar processes for hematopoietic stem cell
preparation.

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92. Indian Scenario
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93. Denvax TM
Customized dendritic cell therapy for treating
cancers in India
DENVAX is administered as an infusion in
100ml DNS, in twenty minutes
www.dendriticcellresearch.com
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95. 24-Feb-17
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96. QUALITY CONTROL
Sterility Bacteria, fungus, mycoplasma negative
Purity > 50%HLA DR, CD86, CD11c/CD123 positive
Viability
> % 70 by trypan blue exclusion or propidium iodide
stain
Pyrogenity Endotoxin negative by LAL
Potency
CD 45 positivity, mixed lymphocyte reaction, Costim
assay, high level of target protein expression
Ovali et al; Dendritic cell therapy: ISBTSS:
2007; 2; p 130-134
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97. Optional validation criteria:

a)Stability of DC phenotype- determined after 1 & 2 days culture with or
without cytokines.
Wash out test: DCs should maintain their viability, phenotype and
morphology over 2 days in medium without cytokines – C/c feature of
Mature DC
b) Induction of immune response- mixed lymphocyte reaction- T cell
proliferation at DC/PBMC ratio of 1/20 in at least one donor.
Recognition of loaded antigen by T cells, determined by cytokine assay
before freezing.
c) Antigen loaded state – antigen specific stimulation assay: tests ability
of antigen loaded DCs to stimulate antigen specific T cells. 24-Feb-17
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98. ◻"Quality control" refers to the vaccine itself, methods to
monitor the immune response, as well as the study design
◻Monitoring the quality of the DC vaccine by reliable,
reproducible, and relatively simple tests to maintain their
feasibility.
◻DCs should be clearly positive for CD83, CD80, CD86,
and DC-lamp.
◻ The majority of DCs are expected to be negative for
CD14 and MCSF-R
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99. ◻The cells should be stable in a prolonged in vitro
culture even without cytokines and should exhibit a
potent T cell stimulatory capacity
◻ The cells should also exhibit the typical DC
morphology (non-adherent cells with large, mobile
veils).
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101. 24-Feb-17
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102. 24-Feb-17
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103. Conclusion
◻DC-based immunotherapy represents a promising way
to fight cancer as DCs play a key role in inducing
antitumor immunity
◻Early clinical studies have demonstrated that
vaccination with DCs can induce immunological and
clinical responses in patients with advanced cancer
◻Additionally, DC vaccination may be a prophylactic
and therapeutic option for many infectious diseases that
are otherwise difficult to treat or incurable.
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104. ◻There are still many open questions concerning the
optimal vaccination strategy, but combining the
increasing knowledge in DC biology and new
techniques for immune monitoring will help us to
improve the efficacy of this new therapeutic
concept
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105. ◻In summary, DCs are being actively pursued as a means to
induce immunity in human patients.
◻Since DCs are potent regulators of the immune system,
much research is being done to try to understand how DCs
can be harnessed to induce immunity. While our
understanding of DCs has evolved tremendously in the 40
years since they were first described, the use of DCs as a
form of immunotherapy is in it’s infancy. We are poised to
learn whether and how DCs will be useful as a tool in our
arsenal to exploit human immunity against disease
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107. References
1.RALPH STEINMAN AND THE DISCOVERY OF
DENDRITIC CELLS, Nobel Lecture, Dec 7, 2011; MICHEL C. NUSSENZWEIG
2. Karolina Palucka; Cancer immunotherapy via dendritic cells; nature reviews Cancer
3. Kamila Wojas, Dendritic cells in cancer immunotherapy— a short review; VIA Medica
4. Alessio Nencioni, Cellular Immunotherapy with Dendritic Cells in Cancer: Current Status; Stem
Cells
5. Eric Weilder; Dendritic Cells – a basic review; ISCT, 2003
6. Dendritic Cell Vaccine and its Application in Cancer Therapy;
International Journal of Vaccines & Vaccination
7. D. H. Yi & S. Appel; Current Status and Future Perspectives of Dendritic
Cell–Based Cancer Immunotherapy, 2013
8. http://lab.rockefeller.edu/steinman/dendritic_intro/maturationDendritic
9. http://www.dendriticcellresearch.com/success_stories - DENVAX
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108. •Thank
you!!!!!!!
Thank
you!!!!!!!
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