Therapeutic vaccines

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A therapeutic vaccine is a vaccine which is administered after a disease or infection has already occurred. A therapeutic vaccine works by activating the immune system of a patient to fight an infection. A therapeutic vaccine differs from a prophylactic vaccine in that prophylactic vaccines are administered to individuals as a precautionary measure to avoid the infection or disease while therapeutic vaccines are administered after the individual is already affected by the disease or infection. A therapeutic vaccine fights an existing infection in the body rather than immunizing the body for protection against future diseases and infections. [1] Therapeutic vaccines are mostly used against viral infections. Patients affected with chronic viral infections are administered with therapeutic vaccines, as their immune system is not able to produce enough efficient antibodies. [2]

Contents

Provenge, developed by Dendreon, was the first therapeutic vaccine approved by the FDA in 2010. This therapeutic vaccine helped in treating prostate cancer where patients' own white blood cells (WBCs) were taken and treated with drug (vaccine) to train them to differentiate and fight cancer cells. [3]

Functionality

Therapeutic vaccines are a new form of vaccines that are mostly being used for viral infections and various types of cancers. A therapeutic vaccine helps an immune system to recognise a foreign agent such as cancerous cells or a virus. The specific type of therapeutic vaccines include antigen vaccines. In case of antigen vaccines, the body is introduced to a foreign agent to activate the immune system so that it recognizes the agent when later encountered. [4]

Types

There are two types of therapeutic vaccines:

Autologous vaccines

Autologous means 'derived from oneself' – an autologous vaccine is a personalized vaccine which is made from an individual's own cells which could be either cancer cells or immune system cells. [5]

Allogeneic vaccines

Allo means 'other'. Allogeneic vaccines are primarily cancer vaccines which are made from a different individual's cancer cells which are grown in a lab. [6]

How therapeutic vaccines differ from prophylactic vaccines

The concept of therapeutic vaccines is different. When a person hears the word vaccine, the thought of prevention against a certain disease comes to mind. However, therapeutic vaccines are a method of treatment. Like any other vaccine, the immune system is regulated against a specific type of target. The main goal is to enhance the immune system activity. This type of vaccine can be employed for the treatment of various type of diseases and viral infections. [7] [8] Efforts are being made to develop vaccines against various fatal diseases such as HIV, cancer, dengue fever, cholera, Diphtheria, etc.[ citation needed ]

Therapeutic vaccines against HIV

HIV has no vaccine up until now, but therapeutic vaccines could be the breakthrough for HIV. Such vaccines would enhance affected patients immune systems to fight the disease. Many researchers are trying to develop and test therapeutic HIV vaccines in order to slow the HIV progression to AIDS. People affected with HIV normally have HIV at undetectable level, which is detected by use of antiretroviral therapy (ART). If therapeutic vaccines for HIV work out, many lives will be saved. [9] Many clinical trials are being conducted for HIV therapeutic vaccines, such as those conducted by AIDSinfo, summaries for their trials are available at their website. [10]

Therapeutic vaccine against cancer

Cancer is the major cause of deaths in the recent era. Cancer types and stages have enhanced with time and so has efforts to treat cancer. Currently, there are about 369 cancer vaccine studies ongoing all around the world. [11]

There are three cancer therapeutic vaccines which are approved by USA Food and Drug Administration, as following;

Provenge is Sipuleucel-T, a dendritic cell based vaccine for prostate cancer. [12] Bacillus Calmettle-Guerin (TheraCys) is a live attenuated vaccine which makes use of Mycobacterium bovis strain for bladder invasive cancer. Talimogene laherparepvec (T-VEC or Imlygic) is a vaccine for advanced oncolytic melanoma [13]

Related Research Articles

<span class="mw-page-title-main">Natural killer cell</span> Type of cytotoxic lymphocyte

Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system. They belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, stressed cells, tumor cells, and other intracellular pathogens based on signals from several activating and inhibitory receptors. Most immune cells detect the antigen presented on major histocompatibility complex I (MHC-I) on infected cell surfaces, but NK cells can recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class I. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.

An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune system responses. Oncolytic viruses also have the ability to affect the tumor micro-environment in multiple ways.

Leukapheresis is a laboratory procedure in which white blood cells are separated from a sample of blood. It is a specific type of apheresis, the more general term for separating out one particular constituent of blood and returning the remainder to the circulation.

<span class="mw-page-title-main">Viral vector</span> Biotechnology to deliver genetic material into a cell

Viral vectors are modified viruses designed to deliver genetic material into cells. This process can be performed inside an organism or in cell culture. Viral vectors have widespread applications in basic research, agriculture, and medicine.

CD4 immunoadhesin is a recombinant fusion protein consisting of a combination of CD4 and the fragment crystallizable region, similarly known as immunoglobulin. It belongs to the antibody (Ig) gene family. CD4 is a surface receptor for human immunodeficiency virus (HIV). The CD4 immunoadhesin molecular fusion allow the protein to possess key functions from each independent subunit. The CD4 specific properties include the gp120-binding and HIV-blocking capabilities. Properties specific to immunoglobulin are the long plasma half-life and Fc receptor binding. The properties of the protein means that it has potential to be used in AIDS therapy as of 2017. Specifically, CD4 immunoadhesin plays a role in antibody-dependent cell-mediated cytotoxicity (ADCC) towards HIV-infected cells. While natural anti-gp120 antibodies exhibit a response towards uninfected CD4-expressing cells that have a soluble gp120 bound to the CD4 on the cell surface, CD4 immunoadhesin, however, will not exhibit a response. One of the most relevant of these possibilities is its ability to cross the placenta.

Vaccine therapy is a type of treatment that uses a substance or group of substances to stimulate the immune system to destroy a tumor or infectious microorganisms such as bacteria or viruses.

Dendreon is a biotechnology company. Its lead product, Provenge, is an immunotherapy for prostate cancer. It consists of a mixture of the patient's own blood cells that have been incubated with the Dendreon PAP-GM-CSF fusion protein. Phase III clinical trial results demonstrating a survival benefit for prostate cancer patients receiving the drug were presented at the AUA meeting on April 28, 2009. After going through the approval process, Provenge was given full approval by the FDA on April 29, 2010. Dendreon's stock value fell 66% on August 4, 2011, after abandoning its forecast for its debut drug Provenge.

Active immunotherapy is a type of immunotherapy that aims to stimulate the host's immune system or a specific immune response to a disease or pathogen and is most commonly used in cancer treatments. Active immunotherapy is also used for treatment of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion disease, and multiple sclerosis. Active immunotherapies induce an immune response through direct immune system stimulation, while immunotherapies that administer antibodies directly to the system are classified as passive immunotherapies. Active immunotherapies can elicit generic and specific immune responses depending on the goal of the treatment. The categories of active immunotherapy divide into:

Sipuleucel-T, sold under the brand name Provenge, developed by Dendreon Pharmaceuticals, LLC, is a cell-based cancer immunotherapy for prostate cancer (CaP). It is an autologous cellular immunotherapy.

Neuvenge, Lapuleucel-T, is a therapeutic cancer vaccine (TCV) in development by Dendreon (DNDN). It uses the "immunotherapy platform approach" first successfully demonstrated on the U.S. Food and Drug Administration (FDA)-approved TCV Provenge. It was first tested on breast cancer patients with tumors expressing HER2/neu, and is now scheduled to be tested on bladder cancer patients.

Gustav Gaudernack is a scientist working in the development of cancer vaccines and cancer immunotherapy. He has developed various strategies in immunological treatment of cancer. He is involved in several ongoing cellular and immuno-gene therapeutic clinical trials and his research group has put major efforts into the development of various T cell-based immunotherapeutic strategies.

<span class="mw-page-title-main">Talimogene laherparepvec</span> Gene therapy medication

Talimogene laherparepvec, sold under the brand name Imlygic, is a biopharmaceutical medication used to treat melanoma that cannot be operated on; it is injected directly into a subset of lesions which generates a systemic immune response against the recipient's cancer. The final four year analysis from the pivotal phase 3 study upon which TVEC was approved by the FDA showed a 31.5% response rate with a 16.9% complete response (CR) rate. There was also a substantial and statistically significant survival benefit in patients with earlier metastatic disease and in patients who hadn't received prior systemic treatment for melanoma. The earlier stage group had a reduction in the risk of death of approximately 50% with one in four patients appearing to have met, or be close to be reaching, the medical definition of cure. Real world use of talimogene laherparepvec have shown response rates of up to 88.5% with CR rates of up to 61.5%.

<span class="mw-page-title-main">Lauren V. Wood</span> American allergist, immunologist

Lauren V. Wood is an American allergist, immunologist, and staff physician at the National Cancer Institute (NCI) at the National Institutes of Health (NIH) in Bethesda, Maryland, where she has served as a principal investigator. She is known for conducting studies of vaccines for cancer, Human papillomavirus (HPV), Hepatitis C, and HIV especially for use with children, teens and young adults. She holds the rank of captain in the U.S. Public Health Service (PHS).

Cryoimmunotherapy, also referred to as cryoimmunology, is an oncological treatment for various cancers that combines cryoablation of tumor with immunotherapy treatment. In-vivo cryoablation of a tumor, alone, can induce an immunostimulatory, systemic anti-tumor response, resulting in a cancer vaccine—the abscopal effect. Thus, cryoablation of tumors is a way of achieving autologous, in-vivo tumor lysate vaccine and treat metastatic disease. However, cryoablation alone may produce an insufficient immune response, depending on various factors, such as high freeze rate. Combining cryotherapy with immunotherapy enhances the immunostimulating response and has synergistic effects for cancer treatment.

The dendritic cell-based cancer vaccine is an innovation in therapeutic strategy for cancer patients.

Julianna Lisziewicz is a Hungarian immunologist. Lisziewicz headed many research teams that have discovered and produced immunotheraputic drugs to treat diseases like cancer and chronic infections like HIV/AIDS. Some of these drugs have been successfully used in clinical trials.

The Immune Response Corporation (IRC) was a pharmaceutical company that worked in the development immunotherapeutic products. The firm was founded by Jonas Salk and Kevin Kimberlin when Kimberlin, "asked Salk to become lead scientific advisor for a new biotech company specializing in 'anti-idiotypes,' a novel vaccine technology." Salk called the proposal "liberating."

References

  1. ↑ "Preventive vaccine vs therapeutic vaccine | Fondation québecoise du Sida". Archived from the original on 2019-11-10. Retrieved 2019-11-10.
  2. ↑ Shimasaki, Craig (2014). "Understanding Biotechnology Product Sectors". Biotechnology Entrepreneurship. pp. 113–138. doi:10.1016/B978-0-12-404730-3.00009-9. ISBN   9780124047303. S2CID   107391475.
  3. ↑ Gulley, James (2012). "Therapeutic vaccines The ultimate personalized therapy?". Human Vaccines & Immunotherapeutics. 9 (1): 219–221. doi:10.4161/hv.22106. PMC   3667942 . PMID   22995839.
  4. ↑ Madan RA, Gulley JL, Fojo T, Dahut WL (2010). "Therapeutic cancer vaccines in prostate cancer: the paradox of improved survival without changes in time to progression". Oncologist. 15 (9): 969–975. doi:10.1634/theoncologist.2010-0129. PMC   3228037 . PMID   20798195.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ↑ Sondak, Vernon K.; Sabel, Michael S.; Mulé, James J. (1 April 2006). "Allogeneic and Autologous Melanoma Vaccines: Where Have We Been and Where Are We Going?". Clinical Cancer Research. 12 (7): 2337s–2341s. doi: 10.1158/1078-0432.CCR-05-2555 . hdl: 2027.42/39209 . PMID   16609055.
  6. ↑ Hanna, Michael G. (27 October 2014). "Immunotherapy with autologous tumor cell vaccines for treatment of occult disease in early stage colon cancer". Human Vaccines & Immunotherapeutics. 8 (8): 1156–1160. doi:10.4161/hv.20740. PMC   3551893 . PMID   22854664.
  7. ↑ Griffin, R. Morgan (2006). "Treating Disease With Vaccines". WebMD. Archived from the original on 2021-11-01. Retrieved 2021-04-21.
  8. ↑ Dr. James W. Hodge, Dr. Chandan Guha, Dr. Jacques Neefjes (2008). "Synergizing Radiation Therapy and Immunotherapy for Curing Incurable Cancers: Opportunities and Challenges". Oncology. 22 (9): 1064–1084. PMC   3474236 . PMID   18777956.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ↑ Gina M Graziani, Jonathan B Angel (2015). "Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions". Journal of the International AIDS Society. 18 (1): 20497. doi:10.7448/IAS.18.1.20497. PMC   4641978 . PMID   26561337.
  10. ↑ Clinical trial number NCT01103687 for "Evaluating the Safety and Immune Response of an Adenovirus-Based HIV Vaccine in HIV-Uninfected Adults" at ClinicalTrials.gov
  11. ↑ Margaret E. Gatti-Mays, Jason M. Redman, Julie M. Collins, Marijo Bilusic (2017). "Cancer vaccines: Enhanced immunogenic modulation through therapeutic combinations". Human Vaccines & Immunotherapeutics. 13 (11): 2561–2574. doi:10.1080/21645515.2017.1364322. PMC   5703410 . PMID   28857666.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ↑ Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators (2010). "Sipuleucel-T immunotherapy for castration-resistant prostate cancer". New England Journal of Medicine. 363 (5): 411–22. doi: 10.1056/NEJMoa1001294 . PMID   20818862. S2CID   12168204.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ↑ Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS (2015). "Talimogene laherparepvec improves durable response rate in patients with advanced melanoma". Journal of Clinical Oncology. 33 (25): 2780–88. doi: 10.1200/JCO.2014.58.3377 . PMID   26014293. S2CID   23663167.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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