by Devika Godbole and Nakiya Lokhadwala
T.Y.B.Sc Department of Biotechnology DES Fergusson College, Pune. For BTH3507
Blog Category: Cancer Biology
Cells grow, divide and replace each other in the body. As new cells form, the old ones die. The National Cancer Institute defines tumor as - ‘an abnormal mass of tissue that results when cells divide more than they should or do not die when they should. A tumor develops when cells divide too quickly. Tumors can vary in size from a tiny nodule to a large mass. There are two main types of tumors. Benign tumors are non-cancerous. The cells of this type are localized and small in size. Malignant tumors are cancerous. The cells can grow and spread to other parts of the body. A person can sometimes see a swelling or feel the lump of a tumor but others will only show up on imaging tests like MRI. A biopsy is necessary to determine the type of the lump.
Tumor vaccines represent another approach of arranging the immune system’s disease fighting forces against cancer. Some of these vaccines consist of cancer cells, parts of cells or immune stimulating proteins called antigens. Others involve removing some of a patient’s white blood cells and exposing them to a protein from the cancer, along with a stimulatory molecule. There are two types of cancer vaccines namely:
● Preventive vaccines
● Treatment vaccines
Preventive vaccines:
Usually, prevention vaccines are given to people to develop an immune response against a particular virus. Similarly, these cancer prevention vaccines are given to healthy people to avoid development of certain cancers. Like vaccines for chickenpox or the flu, these vaccines protect the body from viruses that can cause disease. A person has to get the vaccine before the virus infects him or her. Otherwise the vaccine will not work.
There are two types of cancer prevention vaccines approved by the U.S. Food and Drug Administration (FDA)
● Hepatitis B vaccine: This vaccine prevents hepatitis B virus (HBV) infection. Long lasting infection with HBV can cause liver cancer
● HPV vaccine: This vaccine protects against the human papillomavirus (HPV). If the virus is long lasting, it can cause some types of cancer like cervical cancer. The FDA has approved HPV vaccines to prevent cervical cancer, vaginal cancer, anal cancer and Genital warts.
Some examples of preventive vaccines are Cervarix, Gradasil, etc
Following diagram depicts two pathways after HPV infection via genital-to-genital contact in the cervical cells.
Treatment vaccines:
Cancer immunotherapy is the artificial stimulation of the immune system to treat cancer, improving on the immune system’s natural ability to fight the disease. Cancer treatment vaccines are also called therapeutic vaccines which is a type of immunotherapy. The vaccines work to boost the body’s natural defence to fight cancer. These vaccines are given to those who are already diagnosed with tumors. The vaccine may stop tumors from growing or spreading, destroy any cancer cells still in the body after the treatment has ended, and prevent cancer relapse. Some examples of therapeutic vaccines are Bacillus Calmette Guerin (BCG), Sipuleucel-T, etc. The two types of treatment vaccines are:-
1) Autologous cancer vaccines: Autologous means “derived from oneself” – so an autologous vaccine is a personalized vaccine made from an individual’s own cells—either cancer cells or immune system cells. To make an autologous vaccine, cells from a person’s tumor are removed from the body and treated in a way that makes them a target for the immune system. They are then injected into the body, where immune cells recognize them, disable them. Ideally, memory immune cells would persist in the body and be able to respond if cancer cells returned. The goal may be to treat the cancer present in the body or to prevent tumors from recurring after more conventional cancer treatments like surgery, radiation, or chemotherapy have eliminated most of the cancer cells. Although many clinical trials are going on and have reached phase 2 and phase 3 none of them have been licensed. Another approach towards autologous vaccines has been used. Here an individual’s own immune cells are used to make the vaccine. The US FDA has licensed one autologous vaccine made from immune cells. Sipuleucel-t (Provenge®) is an autologous immune cell prostate cancer vaccine. It has been shown in clinical trials to extend life for men with treatment-resistant metastatic prostate cancer.
Sipuleucel-T is produced and works in the following manner:
1) Patient goes to the lab to get blood drawn.
2) Lab isolates a certain type of immune cell from the patient's blood.
3) Lab technicians expose the immune cells to a prostate-cancer antigen fused with an immune-cell stimulator.
4) Treated immune cells are infused back into the patient.
5) Treated immune cells signal other immune cells to attack prostate cancer cells.
Clinical Pharmacology:-
The development of sipuleucel-T vaccine was based on the concept of antigen-presenting cells (APCs). These cells “present” antigens in a form that T cells can recognize. APCs are a group of white blood cells (WBCs) that include dendritic cells, macrophages, and B lymphocytes (B cells). These cells express major histocompatibility complex (MHC) class II and MHC class I molecules, which can stimulate CD4+ T-helper cells and CD8+ T cytotoxic cells, respectively. Invaders are first engulfed and brought inside the cell. They are then broken down into their antigens and are moved to the cell surface, where they are recognized by T-cell receptors.
After a certain type of immune cells have been isolated from the patient the immune cells are exposed to a prostate cancer fusion protein which is prostatic acid phosphatase (PAP), and it is infused with an immune- cell stimulator, granulocyte–macrophage colony-stimulating factor (GM–CSF). After this they are cultured and then they are infused back into the patient.
Image courtesy: www.urotoday.com
2) Allogeneic cancer vaccines: Allo means “other” Allogeneic cancer vaccines are made by growing non-self-cancer cells in a laboratory. Several allogeneic cell vaccines have been tested and are being tested, including the vaccines used to treat melanoma (skin cancer), pancreatic cancer, leukemia and prostate cancer. Allogeneic vaccines are appealing because they are less costly to develop and produce compared to autologous vaccines. So far, none has shown to be effective enough to be licensed. Several allogeneic vaccines are tested at early stages.
The autologous and allogeneic vaccines are whole-cell vaccines i.e. they are made up from entire cancer cells or immune system cells. But some cancer cells in development are made up from parts of cancer cells. These parts are proteins from cells or even short chains called peptides. The proteins or peptides can be delivered as vaccines coupled with carriers or in combination with immune-stimulating molecules. These vaccines are still in the clinical trial phase.
Some researchers think cancer treatment vaccines may work better for smaller tumors or early-stage cancers. Clinical trials are important for learning more about cancer vaccines. Researchers are testing vaccines for several types of cancers .In summary, a host of commercial, manufacturing, regulatory, clinical, laboratory and operational issues need to be addressed during the typical clinical development path for a novel cancer vaccine product demanding careful and continuous risk evaluation and considerable expertise from developers.
References:
● Chunqing Guo, Masoud H. Manjili, John R. Subjeck, Devanand Sarkar, Paul B. Fisher, Xiang-Yang Wang, 2013, Therapeutic Vaccines: Past, Present and Future, doi: 10.1016/B978-0-12-407190-2.00007-1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721379/
● Alex Kudrin, Human Vaccines and Immunotherapeutics, 2012 sept , 1335–1353. doi: 10.4161/hv.20518 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579919/
● Olivera J. Finn, 2015 Aug 1, Vaccines for cancer prevention: A practical and feasible approach to the cancer epidemic, doi: 10.1158/2326-6066, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163937/
● E. Nößner, D. J. Schende, 1999 Gene Therapy, chapter Autologous and Allogeneic Tumor Cell Vaccines
● Video: Made on Windows Live Movie Maker.
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