Dr. Bindu S Microbiologist

1. IMMUNOTHERAPEAUTIC STRATEGIES AGAINST
PATHOGENS
Presentor : Bindu S
Division of Veterinary Microbiology

2. Outline
 History
 Introduction
 Immunotherapeutic strategies
 Applications
 Pros and cons of immunotherapy
 Conclusion

3. History
William Bradley Coley : Father of Immunotherapy
Cancer patients treated by injection
with coley’s toxin which contained
heat killed microorganisms
Streptococcus pyogens and Serratia
marcesens
Edward F Mccarthy (2006):The toxins of william B coley and treatment of soft tissue
sarcoma

4. Introduction
• Immunotherapy
Immunotherapy , also called biologic
therapy, is a type of treatment designed to
boost the bodys natural defenses to fight
against pathogens .
It uses substances either made by the body
or in a laboratory to improve or restore
function of immune system
-Jacobson et al.,2002: Immunotherapy for infectious diseases

5. Immunotherapeutic Strategies
Immunotherapy
Active
Specific
Therapeutic
vaccines , heat
shock proteins
Non specific
Cytokines,
adjuvant
stimulation
Passive
Specific
Antibodies ,
toxins, bispecific
antibodies Tcells
Nonspecific LAK cells
Combined
LAK cells and
bispecific antibody
Immunomod
ulator
- Addis Beyene et al.,2015: Immunotherapeutic srategies against infectious and non
infectious diseases

6. Active
Dendritic cell therapy
Check point blockade
TNF and INF therapy
Passive
LAK and TIL cell
activation
Monoclonal antibody

7. Dendritic Cell Based Immunotherapy
 Isolating Dendritic cell
 Introducing antigen ex
vivo
 Secrete GM CSF
 Dendritic cells hold on
to the MHC molecules
 Transfection to patients
 Activated cells present
antigen to lymphocytes
Intiates cytotoxic
response against antigens
-Kedar E,Klein E(1992): Cancer immunotherapy.In:Roitt,4th edition.PP:386-392

8. CTLA-4 and PD-1/PD-L1 Checkpoint
Blockade
 Provides perfect signal to CTL by GM CSF transduced vaccine with CTLA 4
blockade and kills the antigen
 MEK inhibition may increase the antigen recognition and antigen presentation
 Targetting MEK and PD-L1 have a synergistic effect on restoring body’s Immune
response
- Addis Beyene et al.,(2015): Immunotherapeutic srategies against infectious and non
infectious diseases
Brea EJ, Oh CY, Manchado E, et al.,(2016): Cancer Immunology;4:936-947

10. TNF Therapy
Supplementation
of TNF
-Elizebath R burton et al.,2009: Targetting
TNF in cancer therapy

11. Interferon Therapy
 Acts as antiproliferative agent
 Increased effect on MHC class1 expression
 Involves in activation of NK cells and macrophages
Injecting
interferon
Higher
expression of
MHC 1
Antigen easily
recognised
Killer cells
destroy by
secreting toxic
substance
-Kedar E,Klein E(1992): Cancer immunotherapy.In:Roitt,4th edition.PP:386-392

12. Invitro Activated LAK and TIL cells
Lympthocytes culture with IL-2
that develops to NK cells
Express NK cells in presence of
antigen
Modified into lymphocyte
activated killer cells
Destruction of infectious agent
-Kedar E,Klein E(1992): Cancer immunotherapy.In:Roitt,4th edition.PP:386-392

13. Monoclonal Antibody
Mab
Naked Mab
Markers for
destruction
Activation blockers
Conjugated Mab
- Addis Beyene et al.,2015: Immunotherapeutic srategies against infectious and non
infectious diseases

14. Naked Monoclonal Antibody
 Naked Mab works in different ways.
 Some may boost immune response against
antigen.
 Others by blocking specific proteins that help to
foreign agent.
Boost up

15. Conjugated Monoclonal Antibody
 Mab’s are attached to drugs, toxins
or radioactive substance
 Act as homing devices to take these
substances to reach target cell

16. Mechanism of Action of Mab
• Direct cytotoxic action on antigen
• ADCC mediated target cell killing
• Use of cytokines genetically linked to Mab to induce
NK cell and T cell proliferation
• The antigen specifically of the Mab to deliver cytocidal
agents to the surface of antigen
- Addis Beyene et al.,2015: Immunotherapeutic srategies against infectious and non
infectious diseases

17. Adjuvant Mediated Immunity Booster
1. Tumor cells are removed from
affected individual
2. Specific markers (antigens)
are isolated and mixed with
danger signal (adjuvant) to
create vaccine
3. Vaccine is given to patient.
These cancer cells give signal
to T cells to recognize and to
destroy -Guillen,G. et al.,2010:Virus like particle as
vaccine antigen and adjuvants

18. Immunomodulatory Strategies
Inhibition or elimination of endogenous cytokine production
Stimulation or modulation of endogenous cytokine production
General
immunstimula
tory agents
Eukaryotic
source
substance
Biochemical
agents
IFN
GM-
CSF
ILS
TGF
beta
-Addis Beyene et al.,2015:Review on immunotherapeutic strategies against infectious
and non infectious diseases

19. Plasmid DNA Therapy
DNA vaccination is a potent
strategy to stimulate Tcell
responses and introduces strong
Th1 bias into immune responses
- Addis Beyene et al.,2015: Immunotherapeutic srategies against infectious and non
infectious diseases

20. Current Immunotherapeutic Agents In Clinical
Usage for Infectious Diseases
Drug class Agent Target Diseases
Monoclonal
antibody
Rituximab CD20 Post transplant
lymphoproliferative
disorder
T cell therapy Antigen specific
Tcells
EBV , CMV,
Adenovirus, Mucor,
Candida, Aspergillus
Viral and fungal
infection
Pathogen specific
immunoglobulin
Varicello zooster,
influenza, CMV Ig
Varicello,
influenza,CMV
Shingles,
influenza,CMV
Monoclonal
antibdody
Palvizumab F glycoprotein Respiratory synitial
virus
Granulocyte
transfusion
Neutrophils Bacteria , fungi Neutropenic sepsis
Cytokine & CSF IFN gamma,GM-CSF Fungi Post
transplantational
infection
-C. Lee Ventola (2017):Immunotherapy , current strategies and agents

21. Applications
 Viral therapy
 Cancer therapy
 Allergy desensitization therapy
 Helminthic therapy
 Adaptive immunotherapy of gram negative sepsis
 Treatment of equine phycomycosis
- Addis Beyene et al.,2015: Immunotherapeutic srategies against infectious and non
infectious diseases

22. Pros of immunotherapy
 Precise effect on target cell
 Long lasting response
 Can work better with other cancer treatment
like chemotherapy
 Cancer may less likely to return due to
immunomemory
 Alternative when other treatment fails
-Neha pathak(2018): Benefits of immunotherapy

23. Cons of immunotherapy
 Toxicity
 Hypersensitivity
 Graft versus host rejection
 Autoimmunity
 May affects organs and systems
 Sometimes it requires longer time for action
 It may not work in all individuals
- Addis Beyene et al.,2015: Immunotherapeutic srategies against infectious and non
infectious diseases

24. • Immunotherapy is a highly desirable alternative to
current treatment strategies than surgery, radiology
and chemotherapy because it is well suited for
immune boosting and its safe , effective and
protective with low toxicity and a durable treatment
response
• Immunotherapy may be next great hope for cancer
treatment