2. Historical Perspective
• Oldest description of cancer was discovered in Egypt and dates back
to about 3000 BC.
• 1777 Nooth, surgeon to Duke of Kent, inoculated himself with cancer
tissue from patient.
• 1808 Alibert, physician to Louis XVIII, received an injection of breast
cancer material.
• In 1970s, scientists mass produced monoclonal antibodies that are
specifically targeted against cancer cells.
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4. INTRODUCTION
• The aim of cancer vaccines is to stimulate the immune system to be
able to recognise cancer cells as abnormal and destroy them.
• There are two major categories that cancer vaccines fit into:
1.Specific cancer vaccine
2.Universal cancer vaccine
• Each type of cancer vaccine works on the same basic idea that the
vaccine, which contains tumor cells or antigens, stimulates the
patient's immune system, which produces special cells that kill
cancer cells and prevent relapses of the cancer. (In Animation)
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5. Cancer vaccines are medicines that belong to a class of substances known as
biological response modifiers. Biological response modifiers work by
stimulating or restoring the immune system’s ability to fight infections and
disease.
Two broad types of cancer vaccines:
•Preventive (or prophylactic) vaccines
prevent cancer from developing in healthy people.
•Treatment (or therapeutic) vaccines
treat an existing cancer by strengthening the
body’s natural defenses against the cancer.
Cancer vaccines
6. Antitumor response of prophylactic vaccine
• Given to people who have very high risk of developing cancers that have
been diagnosed with premalignant changes in tissues
• Vaccine based antigen along with immunomodulatory is introduced that
activate the Langerhan's cells.
• T cells are activated when the tumor antigen is presented to them along
with B cells that produce tumor specific antibodies
• Clonal expansion is the next process that occurs along with the memory cell
formation.
• In future if tumor start its growth tumor specific memory cells will be
reactivated by the tumor antigen reaching lymph nodes
• Secondary immune response
1.Large number of effector T cells
2.High titer of antibodies
3.Continues activation of DC at the site
• Tumor will not be allowed to grow large and is easily eliminated as a result
of secondary immune response.
7.
8. Anti tumor response of therapeutic
vaccine
• Administered after tumor diagnosis when tumor is interacting with
immune system.
• Vaccine (autologous/defined tumor antigen + immunomodulators) to
activate Langerhan’s cells.
• Taken up by activated Langerhan's cells and presented to T cells
• B-cell activated, clonal expansion, production of tumor specific
antibodies.
• Migration of tumor sensitive T cells at site of tumor metastasis.(attempt
to kill tumor cells expressing vaccine Ag.)
• Immunosuppressive tumor microenvironment suppresses their function.
• Establishment of tumor heterogeneity. Leading to lost of tumor antigen
expression or resistance immune effectors mechanism evading immune
evasion.
• Tumor cells with antigen not recognized by T-cells and Ab. They are
resistant to immune destruction.
9.
10. TYPES OF CANCER VACCINES:
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Types of
Cancer
Vaccines
Types of
Cancer
Vaccines
Dendritic
cell
vaccines
Antigen
vaccines
Tumour
cell
vaccine
DNA
vaccine
Anti
idiotype
vaccine
11. Antigen vaccine
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• These use tumor-specific antigens - proteins displayed on a tumor
cell - to stimulate the immune system.
• By injecting these antigens into the cancerous area of the patient,
the immune system will produce an increased amount of antibodies
or cytotoxic T lymphocytes, also known as killer T cells, to attack
cancer cells that carry that specific antigen.
• Multiple antigens can be used in this type of vaccine to vary the
immune system response.
12. Anti-idiotype Vaccines:
• Some antibodies, called idiotype antibodies, act as antigens,
triggering an immune response.
• Primary target is LYMPHOMA.
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13. Dendritic Cell Vaccines:
• Dendritic cells break the antigens on the cancer
cell surfaces into smaller pieces.
• The dendritic cells then act as most-wanted posters for the immune
system, displaying those antigen pieces to the killer T cells.
• In order to make dendritic cell vaccines some of the patient's
dendritic cells are extracted and immune cell stimulants are used to
reproduce large amounts of dendritic cells in the lab.
• These dendritic cells are then exposed to antigens from the patient's
cancer cells.
• This combination of dendritic cells and antigens is then injected into
the patient and the dendritic cells work to program the T cells.
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14. Tumor Cell Vaccines (Autologous
/Allogeneic
Tumor Cells):
• Autologous and allogeneic tumor cells were one of the first types of
tumor vaccines to be used.
• The main advantage of tumor cell vaccines is that they have all the
relevant tumor antigens needed by the immune system to mount an
effective antitumor response.
• A second advantage is that tumor cell-based immunization allows the
development of cancer vaccines without knowing the specific
antigens.
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15. DNA Vaccines
• Bits of DNA from the patient's cells are injected into the patient,
which instructs the other cells to continuously produce certain
antigens.
• This DNA vaccine increases production of antigens, which forces the
immune system to respond by producing more T cells.
• The idea of these vaccines is that the body would be provided with a
constant supply of antigens to allow the immune response to continue
against the cancer.
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16. Cancer Vaccine Preparation:
• Cancer vaccines are made from the person’s own cancer cells or from
cells that are grown in a laboratory.
• The cancer cells are treated with heat or radiation, then they
become inactive and can be used for vaccine preparation.
• Certain proteins may then be taken from the cancer cells and used to
make a cancer vaccine.
• Often a cancer vaccine will also contain substances that are already
known to boost the immune system, such as BCG.
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18. • Mode of Delivery: Cancer vaccines are usually a liquid which is given
by an intradermal injection.
• The Possible Side Effects: The possible side effects of cancer vaccines
include a skin reaction at the injection site, a skin rash or mild flu-like
symptoms.
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19. Cancer Vaccines Which Are Currently
under Clinical Trials:
• Onyvax: (a monoclonal antibody 105AD7 anti-idiotype vaccine)
• It is used for the treatment of advanced colorectal adenocarcinoma.
• The vaccine is administered endemic together with the BCG vaccine
or intramuscularly together with the alum adjuvant.
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• OncoVAX
• Autologous vaccine for Stage II colon
cancer.
• Received fast-track status from FDA
in 2006.
• STUDY: 254 patients received either
OncoVAX or placebo.
• Improves 5-year survival and
recurrence-free interval.
• 57.1% relative risk reduction.
20. Cancer VAX
• It is being used together with the surgical treatment in the treatment
of melanoma III stage.
• In order to increase the cellular immune response, this vaccine is
given together with the BCG Vaccine.
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NY-ESO-1 Peptide Vaccine
• It is used endermic in the treatment of Soft tissue Sarcoma Stage II-
IV expressing NY-ESO-1,LAGE antigen NY-ESO-1 or LAGE antigen .
• Granulocyte-macrophage colony stimulating factor (GM- CSF) is to be
injected, subcutaneous, in additional to this vaccine.
21. A Monoclonal Antibody 11D10Anti-
idiotype Vaccine and Monoclonal
Antibody 3h1 Anti-idiotype Vaccine
• They are being used in the treatment of the patients with stage II or
IIIA non-small cell lung cancer (T1-3, N1-2, M0)
• It is administered starting from the 14-45 days after operation.
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22. GP100 AND MART-1
• A vaccine therapy using Tyrosinase, GP100 and MART-1
peptides together with the alum adjuvant is being used for the
treatment of the patients with IIB IIC, III, or IV cutaneous
melanoma OR stage III or IV ocular or mucosal melanoma.
• Interleukin-12 and the granulocyte-macrophage colony-
stimulating factor (GM-CSF) are also used beside the vaccine.
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23. ALVAC-CEA/B7.1
• A deactivated strain of a virus, is being tested for the treatment
of metastatic colorectal cancer.
• Virus antigens are identical to the antigens exhibited by
colorectal tumors.
• The vaccine is administered immediately upon diagnosis along
with chemotherapy.
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24. VG-1000 Vaccine
• This vaccine is most beneficial in treating carcinomas and
melanomas.
• Patients subjected to chemotherapy or radiation respond more
slowly to VG-1000 as they have a depressed immune system,
however, patients who have had neither radiation nor
chemotherapy respond favourably indicating it as first-line
treatment for persons with recently diagnosed cancers, as well
as to help prevent recurrence.
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25. HSPPC-96, or Oncophage®
• The vaccine is a heat-shock protein, a class of compounds that has
shown activity as autologous therapy
• The therapeutic agent is derived from and tailored to the tumors of
individual patients.
• The HSPPC-96 vaccine contains antigens extracted from melanoma.
• Some of these antigens, like MART-1 and GP100, are unique to
melanoma; others are found in many types of cancer.
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26. Sipuleucel-T
• Dendritic cell vaccine approved for treatment of
asymptomatic or minimally symptomatic metastatic
castrate-resistant (hormone refractory) prostate cancer.
• Target-prostatic acid phosphatase (PAP), which is found in
95% of prostate cancers.
27. • RESULTS
• In the sipuleucel-T group, there was a relative reduction of 22% in the risk
of death as compared with the placebo group.
• This reduction represented a 4.1-month improvement in median survival.
• The 36-month survival probability was 31.7% in the sipuleucel-T group
versus 23.0% in the placebo group.
• CONCLUSIONS
• The use of sipuleucel-T prolonged overall survival among men with
metastatic castration-resistant prostate cancer.
• No effect on the time to disease progression was observed.
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29. DOSAGE AND ADMINISTRATION
• For intravenous use only.
• Administer 3 doses at approximately 2-week intervals.
• Premedicate patients with oral acetaminophen and an antihistamine.
• Infuse Sipuleucel-T intravenously over 60 minutes.
• The most common adverse reactions (incidence ≥ 15%) are chills,
fatigue, fever, back pain, nausea, joint ache, and headache.
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Note: The three-course treatment will cost $93,000.
32. HPV Vaccine
• Gardasil: The FDA approved Gardasil for people ages 9 to 26 years to
prevent:
• Cervical, vaginal, and vulvar cancers in girls and women
• Anal cancer in women and men
• Genital warts in men and boys
• The vaccine protects against the human papillomavirus (HPV).
• Cervarix: This vaccine also protects against HPV infection. The FDA
approved it for the prevention of cervical cancer in girls and women
ages 9 to 25 years.
• The first HPV vaccine became available in 2006.
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33. • According to Centers for Disease Control and Prevention (CDC)
Guidelines and Advisory Committee on Immunization Practices
(ACIP) November 4,2016.
• HPV vaccination is not currently recommended for women over age
26 years.
• Clinical trials showed that, overall, HPV vaccination offered women
limited or no protection against HPV-related diseases.
• For women over age 26 years, the best way to prevent cervical
cancer is to get routine cervical cancer screening, as recommended.
• Available vaccines protect against either two, four, or nine types of
HPV so they are either Bivalent, Quadrivalent or Ninevalent
respectively.
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34. Gardasil 9
• Gardasil 4 got approval by FDA in 2006
Gardasil 9 in Dec,2014.
• GARDASIL 9 is a vaccine indicated in girls and women 9 through 26
years of age for the prevention of the following diseases:
• Cervical, vulvar, vaginal, and anal cancer caused by Human
Papillomavirus (HPV) types 16, 18, 31, 33, 45, 52, and 58
• Genital warts (condyloma acuminata) caused by HPV types 6 and 11
• GARDASIL 9 is indicated in boys and men 9 through 26 years of age
for the prevention of the following diseases:
• Anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58
• Genital warts (condyloma acuminata) caused by HPV types 6 and 11
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35. 35
Age Regimen Schedule
9 through 14 years 2 dose 0,6 to 12 months
3 dose 0,2,6 months
15 through 26 years 3 dose 0,2,6 months
• Each dose of GARDASIL 9 is 0.5-mL.
• GARDASIL 9 should be administered intramuscularly in the deltoid
region of the upper arm or in the higher anterolateral area of the thigh.
• All three vaccines are given through a series of three injections into
muscle tissue over a 6-month period.
• In October 2016, the FDA approved a 2-dose schedule for boys and
girls initiating vaccination with Gardasil 9 at ages 9 to 14 years (the
second dose is to be administered 6–12 months after the first)
36. Cervarix
• CERVARIX is a vaccine indicated for the prevention of the following
diseases caused by oncogenic human papillomavirus (HPV) types 16 and
18:
• Cervical cancer,
• Cervical intraepithelial neoplasia (CIN) Grade 2 or worse and
adenocarcinoma in situ, and
• Cervical intraepithelial neoplasia (CIN) Grade 1.
• CERVARIX is approved for use in females 9 through 25 years of age.
• Three doses (0.5-mL each) by intramuscular injection according to the
following schedule: 0, 1, and 6 months.
• The preferred site of administration is the deltoid region of the upper
arm.
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37. Role of Adjuvants in cancer vaccines?
• Substances known as adjuvants are often added to vaccines to boost
their ability to induce potent anticancer immune responses.
• Some microbes, such as the bacterium Bacillus Calmette-
Guérin (BCG).
• BCG is used to treat early stage bladder cancer. It is a liquid put into
the bladder through a catheter.
• BCG attracts the body’s immune system cells to the bladder, where
they can attack the bladder cancer cells.
• Treatment with BCG can cause symptoms that are like:
• Flu like symptoms such as fever, chills, and fatigue.
• It can also cause a burning feeling in the bladder.
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38. Side Effects of Cancer Vaccine
• The most commonly reported side effect of cancer vaccines is
• Inflammation at the site of injection, including redness, pain,
swelling, warming of the skin, itchiness, and occasionally a rash.
• People sometimes experience flu-like symptoms after receiving a
cancer vaccine, including fever, chills, weakness, dizziness, nausea or
vomiting, muscle ache, fatigue, headache, and occasional breathing
difficulties.
• These side effects, which usually last for only a short time, indicate
that the body is responding to the vaccine and making an immune
response, as it does when exposed to a virus.
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39. • Thalidomide:
• treatment for multiple myeloma
• Lenalidomide:
• Newer drug , treatment for multiple myeloma
• Bacille Calmette-Guérin:
• treatment of superficial forms of bladder cancer
• Colorectal cancer
• Lung cancer
• Melanoma
• Medicinal mushrooms:
• Agaricus subrufescens -anticancer properties
Other drugs that boost the immune system
42. CONCLUSION:
May be more effective in cancers that are not advanced.
More research still needs to be done including larger
studies.
Researchers are actively trying to overcome hurdles in the
making of these vaccines.
Could make a big impact on our approach to cancer.
Most importantly these vaccines could mean better
quality of life and longer survival for patients!!
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