m pharm

1. IMMUNOTHERAPEUTICS VIGNESH M
1ST M PHARM
PHARMACOLOGY DEPT
GOVERNMENT COLLEGE OF
PHARMACY

2. IMMUNITY
Immunity is defined as the body's ability to protect itself from
an infectious disease. When you are immune to a disease,
your immune system can fight off infection from
it. Immunity is either innate or adaptive.
CLASSIFICATION
Barrier immunity
Innate immunity
Adaptive Immunity

16. IMMUNOTHERAPY
Treatment or prevention of disease (such as an autoimmune
disorder, allergy, or cancer) that involves the stimulation,
enhancement, suppression, or desensitization of the immune
system.

17. Why immunotherapy…….?
 Long lasting effects in cancer patients.
 Had great success in fighting and preventing cancer
disease.
 To reduce the side effects of chemotherapy.
 Non toxic.
 Stop, control or suppress process that permit cancer
growth.
 Boost the immune system to destroy affecting Ag.
 Prevents cancer cells from spreading.
 Enhance the body ability to repair or replace damaged
normal cells.

18. Types of immunotherapeutics
1. Immunostimulants
 Non-specific immunotherapy
 Monoclonal antibody
 Antibody -directed enzyme prodrug therapy
 Immunotoxins
2. Immunomodulators
 Adaptive cell therapy
 Cancer vaccines

19. IMMUNOSTIMULANTS
1. Non – specific immunotherapy
 Use of cytokines and other chemicals that stimulate a
general immune response or removes the blockade of
immune activation against cancer cells.
 Regulates the expression of several immunological
components including histocompatibility complex antigens,
immunosuppressive peptides, proto-oncogenes, cell
proliferation and apoptosis.
 Administered directly into the body or by gene therapy.

20. Examples :-
 IL-2 – induces T –cell immunity against cancer such as
metastatic melanoma and renal cell carcinoma.
 IFN –α2a – hairy cell leukaemia
 IFN-α2b - therapy of AIDS related kaposis sarcoma, hairy
cell leukaemia, follicular lymphoma, melanoma and
multiple myeloma.

21. 2. Monoclonal antibodies
 Used for tagging the cancer cells for immune mediated killing
or altering the cell signalling pathways to inhibit proliferation or
inducing apoptosis.
 Proteins and carbohydrate molecules present on surface of
cancer cells are potential targets for new antibody.
 Receptors on the cancer cell surface are targets for antibodies
and binding leads to inhibition of normal signalling pathway
which could lead to cell survival and proliferation.
Examples:-
 Trastuzumab – ERBB2
 Rituximab - CD20
 Bevacizumab- VEGF
 Panitumab- EGFR

22. Ex :- cetuximab – inhibits epidermal growth factor
Antibodies also used for delivering the drugs to kill
cancer cells by conjugating the antibody to a radioactive
particles, immunotoxins or chemotherapeutic agents [ 90Y-
ibribumomab tiuxetan and 131 I- tositumomab ]

23. Side effects
 Fever , nausea , broncohospasm , dysopnea ,
hypotension, serum sickness, headache...

24. 3. Antibody directed enzyme prodrug therapy
 Antibody is used as vector to transfer an enzyme that
converts prodrug to a cytotoxic agent
 In this method, an Ab-enzyme conjugate is injected –
allowed to localize at the tumour cells depending on the
specificity of the Ab. Prodrug – cytotoxic drug.
Drawbacks
 Immunogenicity of the enzyme
 Short half life of the conjugates
 Little anti-tumour activity

26. 4. Immunotoxins
 Source- plant derived or bacterial toxins
 Targets specific antigen on the surface of cancer
cells.
 These toxins inhibits elongation step of protein
synthesis.
Drawbacks - rapid clearance from blood stream and
immunogenicity.
Ex:- gelonin , ricin , abrin, pseudomonas exotoxin ,diptheria
toxin.

28. IMMUNOMODULATORY
1. Adaptive cell therapy
 Highly effective against metastatic melanoma.
 In this, T – cell of patient having anti-tumour activity are
identified - isolated - grown exvivo - stimulated by tumour
APCs – infused back to the same patient.
 Before infusion, high amounts of tumour infiltrating
lymphocytes is injected to host - to manipulate to increase
the effectiveness of the transferred cells.
 Patient undergo lymphodepletion with either chemotherapy
or body irradiation - eliminates suppressive regulatory T-
cells, competitors of cytokines.

30. 2. Cancer vaccines
Two types- preventive and therapeutic
Preventive vaccine
 Prevents tumourgenesis caused by viral infections.
 These are carcinogenic to viruses such as hepatitis B ,
Epstein bar virus , human papilloma virus , kaposis
sarcoma associated herpes virus.
 Hep –B virus vaccine - hepatocellular carcinoma
 Human papilloma virus vaccine - cervical cancer

31. Therapeutic vaccine
Used to increase an immune response to an existing cancer
cells.
Examples :-
1. Peptide / protein based vaccine
Derived from tumour cells as tumour cell specific
antigens for immunization.
ex:-vitespen – melanoma , locally renal cell
carcinoma.
GP-100 – melanoma

32. 2. Gene therapy based vaccine (viral vector vaccine)
The viral vectors are engineered to encode for specific
tumour antigens for the purpose of stimulating and
enhancing the immune responses against cancer cells.
Advantage - easy gene insertion , low cost , ability to
induce persistant immune response.
Ex:- prostvac – VF - prostate cancer

34. Humanization antibody therapy
 Antibody humanization methods are designed to produce a
molecule with minimal immunogenicity when applied to humans,
while retaining the specificity and affinity of the parental non-
human antibody.
 Humanized antibodies are formed from non-human species
whose proteins sequence have been modified to increase
their similarity to antibodies which are produced naturally in
humans.
 Non human antibodies are immumogenic in nature, hence
humanization is necessary.

36. Technology to produce Antibody
Hybridoma technology using transgenic mouse.
 Human antibody display.
 Recombinant antibodies by cloning v- region genes.
 Memory B-cell immortalization.
 CDR- grafting.

37. Hybridoma technology
 Production of hybrid cells – from spleen cells of
transgenic mice and human cells having antibody
 Fusion - B –cells and myeloma cells to produce
hybridoma
 Production of immortalized hybridoma [ cells that can
replicate in-vitro ]
 Screening of hybridoma for desired specificity
 Production of hybrid - hybridoma Ab by fusing 2 cells
 2 Ab are formed in that one antibody contains 33%
mouse protein [ chimeric Ab ] and antibody contains 5-
10% mouse protein [ humanized antibody ]

39. Memory B- cell immortalization
 This technique involves isolation of human memory B
cells from peripheral blood mononuclear cells of
infected patients.
 Immortalization of B cells using Epstein Barr virus in
the presence of a polyclonal B cell activator [ CpG
oligodeoxynucleotides ]
 Transformed cells - capable of producing human clonal
antibody with desired antigen.
 Culture - supernatants are screened for specific
antibodies.
 Positive culture are cloned and fully humanized.