A Cure Within: Scientists Unleashing the Immune System to Kill Cancers


A Cure Within: Scientists Unleashing the Immune System to Kill Cancer


Activation-induced cytidine deaminase (AICDA): An enzyme that catalyzes the removal of amino groups from the nucleotide base cytosine, converting it to the base uracil.

Adaptive immune response: The arm of the immune system that responds specifically after it encounters a pathogen (as opposed to the innate immune response, which is always primed and ready for general threats).

Allogeneic: Cells or tissues from genetically different individuals of the same species.

Alternative pathway: One of the three complement pathways, it is activated by C3 hydrolysis in the presence of pathogens or foreign materials. Activation does not require formation of an antigen–antibody complex.

Amino acids: The basic building block of proteins. They are characterized by an amine group (–NH2–) and carboxyl group (–COOH–), along with a functional group (–R). Proteins are formed by peptide bonds between amino acids.

Amyotrophic Lateral Sclerosis (ALS): A disease affecting the motor nerve cells of the brain and spinal cord that causes a loss of voluntary muscle function over time.

Antibody: A Y-shaped protein that is produced by B cells in response to a specific antigen. These proteins have the ability to bind to harmful substances produced by pathogens.

Antigen: Any external or internal protein that can cause the production of antibodies by the immune system.

Antigen-presenting cell (APC): An immune cell that has the ability to internalize pathogens and display antigens on its surface. The antigens are presented bound to MHC class II molecules.

Arthus Reaction: A hyper-sensitive reaction to intradermal injection of antigens resulting in inflammation and fluid build-up at the site of injection.

Autocrine: A form of cell signaling in which the cell produces hormones or chemical agents that bind to the same cell’s receptors and cause an effect in that cell.

Autoimmune: A condition wherein the immune system regards a ‘self’ antigen as non-self and causes an immune response.

Autologous: Cells or tissues isolated from a person that are re-introduced back into the same person after manipulation.

B Cells: A type of lymphocyte produced in the bone marrow. These cells have the ability to produce antibodies.

Biomarker: A substance in the body that can be measured to indicate the body’s state.

CD4: A surface marker present on a subset of T cells known as T helper cells. It acts as a co-receptor for the T-cell receptor by binding to MHC class II molecules on cells.

CD8: A surface marker present on a subset of T cells known as cytotoxic T cells. It acts as a co-receptor for the T-cell receptor by binding to MHC class I molecules on cells.

CD19: A surface marker on B cells that functions as a co-receptor for B-cell antigen receptor to reduce the signaling once the B-cell antigen receptor is bound by antigens.

CD28: A surface marker present on T cells that is needed for T-cell activation. In addition to the T-cell receptor binding MHC class II on target cells, CD28 needs to bind its partner molecule (B7 ligands) on the same target cell.

Cancer immunoediting: The process of the immune system fighting and sculpting tumor growth. It consists of three phases: elimination (wherein the immune system removes most of the cancerous cells); equilibrium (wherein the remaining tumor cells co-exist with the immune system); and escape (in which the tumor cells start forming tumor masses aided by the immune system).

cDNA library: A library of complementary DNA (cDNA) fragments that represent the expressed genome of an organism. cDNA fragments are inserted into a vector and cloned to create a cDNA library.

Chemokine: A messenger protein that belongs to the cytokine family of signaling molecules. It can act on neighboring cells to guide them to the target site.

Chimeric antigen receptor: T-cell receptors that are engineered using viral vectors to be specific for a desired antigen. It is composed of protein fragments from different animal species.

Cloning: To make a copy.

Complementary: A nucleotide on one strand with an appropriate nucleotide base on the other: adenine (A) binds to thymine (T; in DNA) or uracil (U; in RNA) and vice versa; guanine (G) binds to cytosine (C) and vice versa. If the nucleotide sequence of one strand is –AGCTGCTTAC–, then the complementary strand would be –TCGACGAATG–.

CRISPR/Cas9: A gene editing technique that allows researchers to manipulate target genes.

Cross-presentation: When antigen-presenting cells present an antigen bound to MHC class I molecules to CD8+ cytotoxic T cells.

Cross-priming: Stimulation of cytotoxic CD8+ T cells by antigen-presenting cells. The outcome of cross-presentation.

CTLA4: The inhibitory homologue of CD28. This molecule can bind to B7 ligands with higher affinity and avidity than CD28, and inhibits T-cell activation.

Cyclosporin: An anti-fungal compound produced by fungi that can suppress the immune system.

Cytokine: A family of signaling molecules that have a conserved structure. These molecules are involved in immune cell signaling.

Cytoplasm: The non-nucleated part of a cell’s interior, which contains proteins, glucose and other nutrients, along with organelles.

Cytotoxic T cells: A subset of T cells that are CD8+ (i.e., express CD8) and can kill damaged or infected cells once activated.

Darwin, Charles: An English scientist who proposed the theory of natural selection to explain the change in species over time.

Dendritic cell: An immune cell that can phagocytize pathogens and dead cells. It also functions as an antigen-presenting cell.

Deoxyribonucleic acid (DNA): Deoxyribonucleic acid is the genetic informational code that dictates gene expression and hence all a cell’s characteristics. Each strand of DNA is composed of multiple subunits (nucleotides), each composed of a sugar molecule (deoxyribose), a phosphate molecule, and one of four nucleotide bases (adenine, guanine, cytosine and thymine).

Expressed sequence tags: Fragments of cDNA clones.

Fab (fragment, antigen binding): The upper, and variable, portion of Y-shaped antibodies. They bind to, and are specific for, specific antigens.

Fc receptor: A receptor present on the surface of some cells capable of binding to the lower portion of Y-shaped antibodies (i.e., the Fc [fragment, crystallizable]).

Gene: A specific set of DNA code that dictates the expression of a specific protein. For gene expression to occur, the information in DNA is transcribed to RNA, which acts as a messenger to translate the genetic code to form a protein.

Graft vs. host disease (GvHD): A medical complication that can arise when tissue from a genetically different person is transplanted to a new host. The donor’s immune cells in the tissue graft recognize the host’s cells as non-self and begin attacking them.

Granulocyte-macrophage colony-stimulating factor (GM-CSF): A cytokine released by immune cells that promotes the proliferation and maturation of macrophages and granulocytes.

HeLa cells: An immortalized line of cervical cancer cells isolated from a person named Henrietta Lacks that have been used for several years by researchers to study human cell biology and cancer biology.

Hematopoietic stem cell: A stem cell found in small numbers in the bone marrow that gives rise to all immune and red blood cells.

Humanized antibody: An antibody isolated from an animal that has been manipulated to contain fragments of human antibodies to reduce immune rejection when administered in humans.

Hybridoma : The technology by which monoclonal antibodies are generated. The method involves fusing a B cell that can produce antibodies towards a specific antigen with a cancer cell myeloma to produce a cancerous B cell that will generate antibodies indefinitely.

Immortalized cells: Cells that can grow and multiple indefinitely because of a mutation.

Immune surveillance: A surveillance process used by the immune system to monitor any abnormal cells. 

Immunoglobulin: Another name for antibody.

In vitro: Literally, in glass (Latin). A process that takes place outside a living organism, e.g., in a test tube or culture dish.

Induced pluripotent stem cells (iPSCs): Differentiated cells that can be regressed to a pluripotent state by the overexpression of certain genes.

Inflammation: A response of the immune system to a pathogen or foreign intruder. The response is mounted to remove the insult.

Innate immune response: The arm of the immune system that is always prepared for an attack and can respond to general threats. It is not specific or selective to threats (as is the adaptive immune response).

Interferon gamma: A damage-signaling cytokine that is released by cells in response to an insult such as a pathogen or virus. This cytokine signals the immune cells to mount an immune response.

Interleukin 2 (IL-2): A cytokine released by T helper cells that is necessary for T cell proliferation, activation, and maturation.

Islet cell: A cell in the pancreas that is found in the pancreatic Islets of Langerhans. These cells produce important hormones that regulate glucose metabolism and growth.

Kinase: An enzyme that can add a phosphate group (from ATP) to another molecule.

Knockout: An organism is which a gene is replaced or disrupted such that it is inactive.

Lamarck, Jean-Baptiste: A French biologist who expanded the field of biology by emphasizing the importance of invertebrates and suggesting that genetic traits are inherited.

Leukapheresis: The process of separating white blood cells from a sample of blood.

Library (phage): A library of proteins that are screened using bacteriophages (i.e., viruses that infect bacteria). A gene of interest is inserted into a virus such that the protein encoded by that gene is displayed on the surface of the virus; the protein thus displayed can then be used as a probe to detect its interactions with other genes and/or proteins.

Ligand: A signaling molecule that can bind to a receptor to initiate intracellular events.

Lupus erythematosus: A disease in which the body’s immune cells attack other body cells (e.g., in the skin, joints, etc.). A telltale characteristic of this disease is the development of a rash shaped in the form of a butterfly on the person’s face.

Lymphocyte: A type of white blood cell. It applies to all cells derived from a common lymphoid progenitor: B cells, T cells and NK cells. B and T cells are involved in the adaptive immune response, whereas NK cells are part of the innate immune response.

Lymphokine-activated killer (LAK) cells: Natural killer cells that target and kill tumor cells after exposure to the cytokine IL-2.

Macrophage: A type of white blood cell. A common myeloid progenitor gives rise to monocytes, which circulate in the blood before residing and maturing in the tissue to give rise to macrophages. These cells are antigen-presenting cells.

Major histocompatibility complex (MHC): A set of protein complexes involved in presenting antigens to T cells. These protein complexes can be different in individuals and determine if the tissue from a donor will be compatible with the recipient.

Mast cells: A type of white blood cell derived from a common myeloid progenitor. These cells have granules that can release histamine and play a role in the allergic response.

Meselson–Stahl experiment: An experiment conducted by Matthew Meselson and Franklin Stahl that demonstrated that DNA replication is semi-conservative i.e., when DNA replicates, each new double-strand of DNA is composed of one original strand, and one newly synthesized.

Metastasis: The process of tumor cells traveling in the body to form secondary tumors in other sites.

Microbiome: The combined genetic material of micro-organisms in an environment.

Monoclonal antibody: An antibody that is specific to a target site on the antigen.

Mutant: Refers to the phenotype of an abnormal form of a naturally occurring (i.e., wild-type) species.

Natural killer (NK) cells: A type of white blood cell derived from the common lymphoid progenitor. It can directly bind to pathogens, tumor cells, and virally infected cells, and kill them.

Neutralizing antibodies: Antibodies that can bind to proteins and inhibit the binding of those proteins to receptors.

Neutrophil: A type of white blood cell derived from the common myeloid progenitor. It is the first responder to injury and can recruit other immune cells to the site of injury. It is the most common type of white blood cell found in the body.

NF-kB: A transcription factor that is involved in cytokine production and cell survival.

Oncogene: A gene that is associated with a high risk of cancer when overexpressed or mutated in the body.

Paracrine: A form of cell signaling in which the cell produces chemical signals that bind to a nearby cell’s receptors and causes an effect in that cell.

Phagocytosis: The process by which a cell engulfs/ingests a pathogen or abnormal cell and breaks it down within the cell to inactivate it.

Pharmacokinetics: The branch of pharmacology that examines how the body reacts to the administration of drugs.

Phosphorylation: The process of adding a phosphate group to a molecule (usually protein).

Pipette: An instrument used to measure out precisely small volumes of liquids, usually in the 0.1–1000-microliter range.

Plasma: The fluid component of blood in which cells are suspended. It accounts for 55% of blood’s total volume and contains dissolved substances such as oxygen, glucose, and proteins.

Protein: A macromolecule composed of amino acids linked together to form complex structures. These are the end products of the instructions of genes.

Receptor: A protein on the surface of a cell or within its nucleus that can bind a ligand to cause signaling events in the cell.

Recombinant (DNA, protein): Not naturally occurring. Usually refers to molecules that are engineered outside the body.

Response Evaluation Criteria In Solid Tumors (RECIST) criteria: A set of rules to characterize how tumors progress during clinical treatment.

Retrovirus: Viruses that have RNA as their genetic material. These viruses contain the enzyme reverse transcriptase that can synthesize a single cDNA strand from the RNA. That single strand of viral cDNA is then converted via the infected cell’s machinery to a double-stranded sequence, and expression of the viral gene then proceeds by the normal cellular mechanisms.

Ribonucleic acid (RNA): RNAs are nucleotides composed of a sugar molecule (ribose), a phosphate molecule, and one of four nucleotide bases (adenine, guanine, cytosine and uracil [as opposed to thymine, as in DNA]). For gene expression to occur, the information in DNA (in the cell’s nucleus) is transcribed to a complementary sequence of RNA, which transports the code to the cytoplasm where it can be used to instruct the cell to form a protein.

Sequence (DNA; amino acid): A particular order of the building blocks of DNA (nucleotide bases) or proteins (amino acids).

Stem cell: An undifferentiated cell that can produce copies of itself or differentiate into a defined cell type.

Subtractive hybridization: A technique to identify and characterize differences between nucleic acid sequences in cells from different tissues, different growth phases, or after treatment with a drug.

T Cells : A type of lymphocyte.

T helper cells: A subset of T cells that are CD4+ (i.e., express CD4) and necessary for activation of cytotoxic T cells.

T-cell receptor (TCR): A receptor present on T cells needed for T-cell activation. The TCR on T cells binds to MHC class I/II molecules on other cells and initiates signaling events in the T cells.

Th17 cells: A subset of T helper cells characterized by their production of the cytokine interleukin-17. These cells are involved in the adaptive immune response.

Thymic selection: A selection process that takes place in the thymus eliminating strongly self-reacting T cells.

Toll-like receptor (TLR): A class of proteins present on immune cells that can recognize structurally conserved molecules released by pathogens. They play a key role in the activation of the innate immune response.

Transcription factor: A type of protein present in the nucleus that can promote or repress transcriptional activity of target proteins.

Translation (clinical): Taking a process or technology from the laboratory bench to the bedside.

Tumor microenvironment: The cellular environment surrounding a tumor, which contains many cell types, stroma, immune cells, and blood vessels.

Tumor-infiltrating lymphocytes (TILs): T cells that have migrated from the blood circulation into the tumor tissue. 

Type I interferon: Proteins released by leukocytes in response to viral infection. This protein enhances the activation of NK cells and macrophages to kill the infected cells.

Type 1 diabetes: A metabolic disease in which the body cannot produce sufficient insulin to regulate glucose levels in the body.

Vector (viral): The DNA backbone of a virus that acts as a vehicle to deliver foreign genetic material into cells, after the harmful viral parts have been removed.

V(D)J recombination: Variable (V), diversity (D) and joining (J) genes can assemble themselves randomly (i.e., recombination) to generate a diverse set of antigen receptors. This recombination process allows B cells and T cells to recognize and battle an indefinite number of antigens.