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Cancer vaccines final

Overview on cancer vaccines, types, techniques and various methods of administering

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Cancer vaccines final

  1. 1. Dr. Ayush Garg 1 CANCER VACCINES
  2. 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. 2
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  4. 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) 4
  5. 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. 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. 7. 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.
  8. 8. TYPES OF CANCER VACCINES: 10 Types of Cancer Vaccines Types of Cancer Vaccines Dendritic cell vaccines Antigen vaccines Tumour cell vaccine DNA vaccine Anti idiotype vaccine
  9. 9. Antigen vaccine 11 • 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.
  10. 10. Anti-idiotype Vaccines: • Some antibodies, called idiotype antibodies, act as antigens, triggering an immune response. • Primary target is LYMPHOMA. 12
  11. 11. 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. 13
  12. 12. 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. 14
  13. 13. 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. 15
  14. 14. 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. 16
  16. 16. • 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. 18
  17. 17. 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. 19 • 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.
  18. 18. 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. 20 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.
  19. 19. 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. 21
  20. 20. 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. 22
  21. 21. 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. 23
  22. 22. 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. 24
  23. 23. 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. 25
  24. 24. 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.
  25. 25. • 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. 27
  26. 26. Indications (NCCN Version 1.2017) 28
  27. 27. 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. 29  Note: The three-course treatment will cost $93,000.
  28. 28.  Mechanism of action of Sipuleucel T ‑
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  30. 30. 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. 32
  31. 31. • 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. 33
  32. 32. 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 34
  33. 33. 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)
  34. 34. 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. 36
  35. 35. 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. 37
  36. 36. 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. 38
  37. 37. • 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
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  40. 40. 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!! 42
  41. 41. THANK YOU 43