this slide contain information about antibody mediated anti-cancer therapy like antibody drug conjugates (ADC), Bispecific monoclonal antibody, Immuno-checkpoint therapy, biomarkers, mechanism of action of all 3 therapies, approved drugs of each category

1. Targeted Anti-Cancer
Therapy
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Presented by :
Jamdhade Vaishali Kailas
2nd Year M. Pharmacy
(Pharmaceutics)
Guided by :
Dr. (Mrs) Chaudhari Pallavi
Dr. D. Y. Patil College of Pharmacy,
Akurdi Pune.
Date: 29/10/2018

2. Content
 Introduction to Cancer
 Targeted Antibody Therapy to Treat Cancer
 Biomarkers
 Antibody Drug Conjugates (ADC)
 Bi-Specific Monoclonal Antibody Therapy
 Immuno- Checkpoint Inhibitor Therapy
 References
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Introduction of Cancer
 Cancer is a group of diseases involving abnormal cell growth with
the potential to invade or spread to other parts of the body.
 These contrast with benign tumors, which do not spread to other
parts of the body.
 Possible signs and symptoms include a lump, abnormal bleeding,
prolonged cough, unexplained weight loss and a change in bowel
movements.

4. Types of Cancer
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Types Cancers Derived From Organs
Carcinoma Epithelial Cells
Breast, Prostate, Lung, Pancreas
And Colon
Sarcoma Connective Tissue Bone, Cartilage, Fat, Nerve
Germ Cell
Tumor
Pluripotent Cells Testicle Or The Ovary
Lymphoma And
Leukemia
Hematopoietic (Blood-forming) Cells That Leave The Marrow And
Tend To Mature In The Lymph Nodes And Blood
Blastoma Immature Precursor Cells Or Embryonic Tissue

5. Biomarkers
 A naturally occurring molecule, gene, or characteristic by which a
particular pathological or physiological process, disease, etc. can
be identified.
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Biomarker Cancer
HER2 Breast cancer
EGFR Non-small-cell lung carcinoma
CA-125 Ovarian Cancer
CA19.9 Pancreatic Cancer
PSA Prostate Cancer

6. Targeted Antibody Therapy
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1. Antibody Drug Conjugates Therapy (ADC)
ADCs are complex molecules composed of an antibody linked
to a biologically active cytotoxic (anticancer) payload or
drug.
2. Bispecifics Therapy
Bispecifics antibody are monoclonal antibody which
simultaneously bind to two different targets.

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3. Immuno- Checkpoint Therapy
 Immuno- Checkpoint Combination
Anticancer drug in combination with other therapy like
chemotherapy, surgery, radiation or with any other
anticancer drug.
 Immuno- Checkpoint Monotherapies
Anticancer drug only.
Targeted Antibody Therapy

8. Antibody Drug Conjugates (ADC)
 ADCs are complex molecules composed of an antibody linked to a
biologically active cytotoxic (anticancer) payload or drug.
 ADCs are intended to target and kill only the cancer cells and spare
healthy cells.
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 Antibody-drug conjugates are
examples of bioconjugates
and immuno-conjugates.

9.  By combining the targeting capabilities of monoclonal antibodies
with the cancer-killing ability of cytotoxic drugs, antibody-drug
conjugates allow for discrimination between healthy and diseased
tissue.
 In contrast to traditional chemotherapeutic drugs, antibody-drug
conjugates target only cancer cells so that healthy cells are less
severely affected.
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Antibody Drug Conjugates (ADC)

10. ADC Linker
 It is a stable link between the antibody and Cytotoxic (anti-cancer)
agent.
 A highly stable ADC linker will ensure that less of the cytotoxic
payload falls off in circulation, driving an improved safety profile,
and will also ensure that more of the payload arrives at the cancer
cell, driving enhanced efficacy.
 Linkers are based on chemical moieties including disulfides,
hydrazones or peptides, or thioethers and control the distribution
and delivery of the cytotoxic agent to the target cell.
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Anticancer drug is coupled to an antibody that specifically
targets a certain tumor marker (Proteins)
Antibodies track these proteins and attach themselves to
the surface of cancer cells.
This biochemical reaction triggers a signal in the tumor cell, which then
absorbs the antibody together with the cytotoxin.
After the ADC is absorption, the cytotoxic drug is released
and kills the cancer.
Mechanism of Action

12. Advantages
 Drug shows lower side effects
 Gives a wider therapeutic window than other chemotherapeutic
agents.
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13. Approved ADC Products
 Only four ADCs have received market approval
 Gemtuzumab Ozogamicin
 Brentuximab Vedotin
 Trastuzumab Emtansine
 Inotuzumab ozogamicin
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14. What is Bi-specific Antibody…?
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 A Bi-specific Monoclonal Antibody (BsMAb, BsAb) is an
artificial protein that can simultaneously bind to two different
types of antigens.
 Bi-specific Antibody =
Two halves of different
Antibodies joined together.

15. Bi-Specific Monoclonal Antibody
 BsAbs are antibodies with Dual
Specificities,
− First specificity is usually against
a tumor antigen.
− The second specificity usually for
an activator on immune effectors
(e.g. CD3 on T cells) but can be
to other targets like ligands,
enzymes, receptors, cytokines.
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Bi-Specific Monoclonal
Antibody

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Bi-Specific Monoclonal Antibody

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Mechanism of Action

18.  Catumaxomab (Removab®, Fresenius Biotech, Trion Pharma,
Neopharm)
 Blinatumomab (Blincyto®, AMG 103, MT 103, MEDI 538,
Amgen)
 Emicizumab (Hemlibra, RG6013, ACE910, RO5534262,
Roche)
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Approved Bispecific antibody

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BsAbs scaffold/Structural formats

20. Immuno- Checkpoint Therapy
 The therapy targets immune checkpoints, key regulators of
the immune system that stimulate or inhibit its actions, which
tumors can use to protect themselves from attacks by the immune
system.
 Checkpoint therapy can block inhibitory checkpoints, restoring
immune system function.
 The first anti-cancer drug targeting an immune checkpoint
was Ipilimumab, a CTLA4 blocker approved in the United States
in 2011
 Currently approved checkpoint inhibitors target the
molecules CTLA4, PD-1, and PD-L1.
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21. 21Mechanism of Action

22. Approved Checkpoint Inhibitors
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Name Target Year of approval
Ipilimumab CTLA-4 2011
Nivolumab PD-1 2014
Pembrolizumab PD-1 2014
Atezolizumab PD-1 2016
Avelumab PD-1 2017
Durvalumab PD-1 2017

23. References
 Dimond Patricia, “Antibody-Drug Conjugates Stage a Comeback -
Technology improvements yield fresh line of anticancer clinical
candidates”, 09 March, 2010.
 Trail Pamela A. et al., “Antibody drug conjugates for treatment of
breast cancer: Novel targets and diverse approaches in ADC
design”, Pharmacology & Therapeutics, Volume 181, January
2018.
 Lambert John M. et al., “Antibody-Drug Conjugates for Cancer
Treatment”, Annual Review of Medicine, 29 January 2018.
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 Marin-Acevedo Julian A. et al., “Next generation of immune
checkpoint therapy in cancer: new developments and challenges”,
Journal of hematology and oncology, 15 March 2018.
 Spiess Christoph et al., “Alternative molecular formats and
therapeutic applications for bi-specific antibodies”, Molecular
Immunology, 27 January 2015.
 Sedykh Sergey E. et al., “Bispecific antibodies: design, therapy,
perspectives”, Drug Design Development Therapy, 22 January 2018.
References

25. Thank You
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