Cancer Vaccines - Innate Immunity

Dr. Catanzaro posted and edited
Written By: Preeti Gokal Kochar

As noted in the previous post, the immune system can be divided into two branches; innate and adaptive, both are involved in fighting cancer.  In this post, the focus will be on the innate branch of the immune system.

Innate immunity is the first line of defense against infectious agents and consists of natural anatomical barriers, such as skin and mucous membranes, physiological barriers like elevation of temperature and acid in the stomach to digest harmful bacteria.  It provides immediate and non-specific defense against infectious organisms.

First characteristic of innate immunity:

It contains phagocytic cells that identifies common features of infectious agents and responds by engulfing bacterial and damaged cells. Phagocytic cells, namely, natural killer cells, dendritic cells and macrophages are the components of the innate immune system most directly involved in tumor immunology.

Second characteristic of innate immunity:

It contains a group of inactive proteins, also known as the complement system, in the blood that is activated in the presence of pathogens and cause cell lysis (cell destruction).  Tumor cells have complement regulatory proteins on their cell surface – proteins that inhibit the activation of complement- and thus escape complement-mediated lysis.

Pattern-recognition receptors, present on the cell surface, and antimicrobial proteins present inside cells, are part of the innate immunity and both target pathogenic bacteria.  

 

The cells of the innate branch have specific roles: 

(1) Natural Killer (NK) Cells
Target cells for NK cells include virally-infected cells and tumor cells.  NK cells don’t require a previous encounter in order to kill tumor cells. These cells have killer activating receptors and cause lysis of target cells using specialized enzymes, perforin and granzymes. Killer inhibitory receptors are also present on the NK cell surface, which prevent lysis of cells with MHC molecules.

 (2) Dendritic Cells (DCs)
Using their pattern-recognition receptors (e.g. toll-like receptors) they detect bacteria and viruses. When encountered, the pathogens are phagocytosed and their proteins are processed and inserted into the DC surface to be presented to T cells. Dendritic cells are professional antigen-presenting cells (APC). They activate helper T cells and Cytotoxic T cells and also activate B cells. They are the first line of defense, because they are found in tissue, i.e. skin, mucosal and respiratory membranes. In the blood, DCs are found in the immature state. 

(3) Macrophages
Macrophages have granules filled with digestive enzymes making it possible for them to fight bacteria and also ingest damaged cells by phagocytosis. In addition to being strongly phagocytic, they present antigens to T cells and thus have a role in adaptive immunity. Macrophages can destroy tumor cells and play a crucial role in the inflammatory response. They are derived from monocytes and have several different names (e.g. Kupffer's cells, histiocytes, alveolar macrophages) depending on the tissue in which tissue they are found.

Cancer Vaccines Con't

Cancer Vaccines con't 

Dr. Catanzaro posted and edited
Written By: Preeti Gokal Kochar



The idea behind the first cancer vaccine is attributed to Coley who, a century ago, observed that his cancer patients benefited from bacterial infection. This prompted him to treat the patients with bacterial extracts. It was not till the 1980s that development of cancer vaccines progressed further. While certain cancers have been successfully treated, progress has been relatively slow. The pace should increase substantially as scientists gain a deeper understanding of how the immune system fights tumors and as the success of the cancer vaccines now available is evaluated.

To learn how cancer vaccines work it is essential to start with insight into the working of the immune system. This review begins with a primer on tumor immunology: the identity and role of each cell involved in recognizing and fighting cancer. The next section explains how tumors actively try to evade the immune system, while the concluding section highlights the strategies used in designing cancer vaccines.

REVIEW SUMMARY

Immunology Primer

The immune system can be divided into two branches; both are involved in fighting cancer.

Innate: Barriers that human beings are born with, including special cells, to fight specific bacteria and other invaders. Natural killer cells are the most significant innate cells that fight cancer directly.

Adaptive: Response that the immune system generates to fight threats as they occur. Lymphocytes are cells involved in fighting these threats. There are two types of lymphocytes, B cells and T cells. Some lymphocytes are cells that trigger immunity, while other lymphocytes are memory cells that allow this adaptive response to occur repeatedly. Cytotoxic T cells are the adaptive cells that directly fight cancer. However, they cannot always recognize cancers and need antigen-presenting cells, dendritic cells, to help them do so.

Properties of Tumors

• Since they resemble normal cells, tumors tend not to trigger the immune system.
• Tumors also actively evade the immune system in different ways.
• Immune cells are not very efficient in detecting tumor growth.

Cancer Vaccines

• Vaccines boost the immune system.
• Preventive vaccines may be used to prevent cancers induced by viruses, such as cervical cancer.
• Most cancer vaccines will probably be therapeutic, used for patients who already have cancer.
• Cancer vaccines modify the immune system response to evoke a strong and specific immune response.
• Types of cancer vaccines include:
  - Tumor antigens used to familiarize the body against the cancer
  - Monoclonal antibodies to mimic tumor antigens
  - Stimulation of the cytotoxic T cells to fight the cancer

Cancer Vaccines

Review Article By Preeti GokalKochar

Cancer Vaccines

Introduction
It is believed that any person who lives long enough will eventually get cancer. In the past, cancer was thought to be invincible. Today with advances in surgery, chemotherapy and radiation therapy, mortality has been reduced. Still, world wide 7 million deaths per year can be attributed to cancer, 12.5% of total deaths. More recently traditional treatments have been supplemented with newer treatments like chemoprevention and cancer vaccines.  The immune system has developed to protect the body against invasion by microorganisms and prevent disease. As more information about immune cells is discovered, scientists have realized that the immune system plays a crucial role in preventing cancer.¹ The implication of this finding is that, by designing cancer vaccines, it is possible to boost the immune system to enable it to combat cancer more effectively.

Traditional vaccines have successfully prevented infectious diseases like small pox. Recently, great progress has been made in the development of vaccines against cervical cancer, caused by human papilloma virus. However, vaccine development of other types of cancers poses more challenges, since most cancers are believed not to be caused by infectious agents, but rather, defects in cellular proteins. Since these proteins are very similar to those found in normal cells, it is difficult to develop vaccines targeting the cancer cells while sparing normal cells. Indeed, most cancer vaccines will be useful for treating cancers in patients already afflicted and not for preventing cancers. The concept of a universal vaccine against cancer is not realistic since there are many types and many causes of cancers.

 To Be Continued