State of art

1. NANOCOMOPSITE(S) FOR IMMUNOTHERAPY

2. INTRODUCTION
Dcs/ Macrophage
x x
Immune inhibition
Inhibitory cytokines
- TGF-b, IL-10, VEGF,
- act on DCs
T-cell inactivation
- dysfunctional DCs
Loss of MHC class I / antigen processing
- MHC class I expression
- TAP etc. (for processing /loading)
- loss of CD8+ T cell recognition
x
x
x
x
Immune-escape of Tumours
.
Cancer : An abnormal growth of cells & uncontrolled cell division.
Melanoma (skin cancer) is one of the major cancer types
and the leading cause of cancer death.

3. Current Approaches and Limitations of Tumor Treatment
Chemo-
therapy
Radiation
Surgery
 Toxicity
(Myelotoxic,
Nephrotoxic);
 Drug resistance.
No guarantee of
complete removal;
 Ineffective for
metastasis.
 Radiation-induced oedema.
 Failure of complete remission
 Also targets dividing normal cells

4. To reduce the side effects associated with To reduce the
side effects associated with current therapy
To increase effectiveness of treatment
To provide patient complete cure
To prevent repetitive cancer
Requirement of Developing New Trends For Cancer Treatment

5. Proposed New Alternative approach of cancer
Treatment : Immunotherapy
Dendritic Cells
Based
Immunotherapy
Safe; Tumor
elimination via
natural
immune
response
No
Toxicity
No chance
to
repetition
 Used for treatment not prevention.
 Enhance the immune response against
cancer.
Based on utilizing the patient’s immune system to fight the cancer

6. Advantages
Greater
variety of
preparation
methods Availability
of various
polymers that
releases drug
in sustain
manner
Improved
stability in
biological
fluids
Tissue
penetrating
ability/ lipid
material able
to fuse with
cell
membrane
Lipid
monolayer
prevents
free
diffusion
More
stable than
liposomes
High structural
integrity
afforded by the
rigidity of the
polymer matrix

7.  Liu, et al., (2015) fabricated the pH-Responsive Poly(D,L-lactic-co-glycolic acid)
nanoparticles with rapid antigen release behaviour promote immune responses
and reported that after immunization (mouse) with pH-responsive PLGA NPs,
induced strong cellular immune responses and offered antibody protection, could
be potentially useful as effective vaccine delivery and adjuvant systems for the
therapy of intracellular infectious diseases and virus infection.
 Jiang et al., (2015), suggested that nasal administration of a galactosylated
liposome vaccine mediates the development of an effective immunity against
tumors and might be useful for further clinical anti-tumoral applications.
 Yoshizaki, et al., (2014) investigated the pH-sensitive polymer-modified
liposomes with cationic lipid inclusion as antigen delivery carriers for cancer
immunotherapy. Experimental results showed that the administration of these
liposomes to mice induced antigen-specific immune responses, which caused
marked therapeutic effects on tumor-bearing mice. Therefore, the cationic lipid-
incorporated pH-sensitive liposomes can engender production of potent antigen
delivery systems, which can contribute to the establishment of efficient cancer
immunotherapy.
 Zhang et al., (2014) studied that the combined formulation (composed of antigen
encapsulated in nanoparticles and antigen mixed with nanoparticles) induced
more powerful antigen-specific immune responses than each single-component
formulation.
LITERATURE REVIEWED

8.  Tel and group (2013) targeted nanoparticles coencapsulated with TLR7 agonist R848 to C-type
lectins DEC-205, DC immunoreceptor, blood DC Ag-2, or the FcR CD32 present on
plasmacytoid DC which resulted in uptake, processing, cross presentation of encapsulated Ag to
both CD4+ and CD8+ T cells, phenotypical maturation as well as robust IFN-α and TNF-α
production.
 Bracci and his colleagues (2013) have reported about the biology of dendritic cell and DC
subset with emphasis of their role in cancer treatment.
 Leonie E Paulis et al. (2013) proposed the important aspects of nanovaccine design for
dendritic cells, including the synergistic and cytosolic delivery of immunogenic
compounds, as well as their passive and active targeting to dendritic cells.
 Segura et al. (2012) analysed the DCs in lymph node and skin-derived migratory DCs and found
that two populations of resident DCs and their two blood subtypes are present in all LNs and
three main populations of skin-derived migratory DCs are present in skin-draining LNs. Further,
they studied the type of immune response generated by various DC subsets.
 Joshia MD et al. (2012) reported the use of particulate carriers like lipid and polymeric
nanoparticles for active and passive targeting of antigens to the dendritic cells and discusses
smart nanocarriers capable of delivering the antigen into the MHC class I pathway for increasing
CTL response.It also emphasizes on the physicochemical parameters of nanocarriers such as
size, surface charge in passive targeting.
 Klippstein R et al. (2010) suggested about latest advances in NP delivery methods targeting
DCs, the mechanisms of action, potential effects, and therapeutic results of these systems and
their future applications, such as improved vaccination strategies, cancer immunotherapy, and
immunomodulatory treatments.
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