Immunology

The immune system is complex and pervasive. It rests on two major pillars: the innate, general immune system and the adaptive, specialized immune system. Both systems work closely and take on different tasks.  The immune system includes numerous cell types that either circulate throughout the body or reside in a particular tissue. Each cell type plays a specific role, with different ways of recognizing problems, communicating with other cells, and performing their functions to prevent or limit infection and tumorigenesis.

 

The innate system is the first line of defense, fast and broadly effective, it consists of several elements: 1) The skin and mucous membranes (external barriers); 2) Leukocytes such as natural killer (NK) cells; 3)Various substances in the blood and in the body fluids such as the complement system.

 

The adaptive immune system is the second line of defense, precision and a long memory, it includes: T and B lymphocytes; Antibodies as soluble proteins in the blood; and Cytokines in the blood and tissue as hormone-like messenger substances.

 

Cancer immunotherapy

Cancer immunotherapy is an emerging form of cancer treatment that uses the power of the body’s own immune system to prevent, control, and eliminate cancer. Furthermore, immunotherapy can educate 1) the immune system to recognize and attack specific cancer cells; 2) Boost immune cells to eliminate cancer; 3) Provide the body with additional components to enhance the immune response against cancer.

Wherever you are on your cancer treatment journey, you may want information on the types of immunotherapy available today. Here we describe some promising approaches that are currently approved by the FDA or being tested in clinical trials.

 

Adoptive cell therapy

Adoptive cell therapy (cellular immunotherapy), is a form of treatment that uses the cells of our immune system to eliminate cancer. Some of the approaches involve directly isolating the immune cells and simply expanding their numbers, whereas other approaches involve genetically engineering the immune cells to enhance their cancer-fighting capabilities. Examples of these type of novel therapies include:

  • TIL – Tumor-infiltrating lymphocyte therapy

  • TCR – Engineered T cell receptor therapy

  • CAR-T – Chimeric antigen receptor T cell therapy

  • NK – Natural killer cell therapy

  • CAR-NK – Chimeric antigen receptor NK cell therapy

 

Antibody therapy

Antibody drugs are a form of cancer immunotherapy treatment that can disrupt cancer cell activity and alert the immune system to target and eliminate cancer cells. Antibodies are proteins that are naturally produced by B cells and serve to protect us against a variety of threats, such as bacteria, viruses, and cancer cells. Antibodies do this by precisely targeting and binding to cell surface markers known as antigens. Mainly three types of monoclonal antibody drugs are currently in clinical use:

  • Monoclonal antibodies (mAbs)

  • Antibody-Drug Conjugates (ADCs)

  • Bispecific antibodies

 

Immunomodulators

Immunomodulators are molecules that act on the pathways that regulate the immune system’s activity. They include checkpoint inhibitors such as PD-1 and CTLA-4 inhibitors (antibodies), cytokines, agonists, and adjuvants.

 

Oncolytic virus therapy

Oncolytic viruses are a form of immunotherapy that uses viruses to infect and destroy cancer cells.

 

Cancer vaccines

Cancer vaccines are a form of immunotherapy that can help educate the immune system about the cancer cell biomarkers or flags so that it can recognize and eliminate them. They include preventive cancer vaccines such as Cervarix® (prevents HPV16/18), therapeutic vaccines such as Sipuleucel-T to treat prostate cancer,  and personalized neoantigen vaccines such as peptide vaccines for melanoma, currently in clinical trials.

 

Immunotherapy for infectious diseases such as COVID-19

Severe cases of COVID-19 exhibit various acute respiratory distress syndrome (ARDS)-like manifestations, unrestrained immune activation also called “cytokine storm”, systematic inflammatory reactions, coagulopathy, etc. 

One of the immunotherapy drugs being tested is a monoclonal antibody against interleukin-6 receptor (IL-6R) called tolucizumab. Excessive IL-6 can cause a “cytokine storm” that activates the coagulation pathway and vascular endothelial cells, while inhibiting myocardial function. Infections by the related SARS-CoV induces a dose-dependent production of IL-6 from bronchial epithelial cells.

 

Vaccines for COVID-19 are being extensively developed in both preclinical and clinical trials. The types of vaccine include: 1) inactivated or weakened virus; 2)viral-vector vaccine, such as measles or adenovirus genetically engineered to produce coronavirus proteins in the body; 3)nucleic acid DNA or RNA vaccine; and 4) protein-based vaccine (protein subunit or virus-like particles). Clinical trials start with small safety studies followed by much larger trials to determine whether a vaccine generates an effective immune response. Hopefully a COVID-19 vaccine can be ready by the end of 2020.

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