CAR T Glossary

(American Cancer Society).
ACT (adoptive cell transfer).
Term coined to encompass CAR T cells and related cellular therapies such as tumor-infiltrating lymphocytes (TIL) and T-cell receptors (TCRs).
adaptive immune system.
Defense employing two types of antigen-specific lymphocytes, B cells and T cells. B cells produce antibodies that combat pathogens in blood plasma and extracellular fluids. T cells combat intracellular pathogens (all viruses, some bacteria and parasites), which can’t be detected by antibodies.
axicabtagene ciloleucel (axi-cel; Kite Pharma).
Also known as KTE-C19. CAR T-cell therapy targeting CD19. In late stages of development; FDA approval anticipated in late 2017, likely as first in class.
ALL (acute lymphoblastic leukemia, acute lymphyocytic leukemia).
Originates in immature lymphocytes in bone marrow, then quickly spreads into blood and beyond (lymph nodes, liver, spleen, CNS). For 2017, ACS estimates 5,970 new cases of ALL and 1,440 deaths in the United States.
AML (acute myeloid leukemia).
Cancer of bone marrow and blood that progresses rapidly without treatment, primarily affecting cells that aren’t fully developed. Accounts for about a third of all cases of adult cases of leukemia in the United States. For 2017, ACS estimates 21,380 new cases, mostly in adults, and 10,590 deaths, nearly all in adults.
Investigational autologous CAR T-cell therapy being developed as treatment for multiple myeloma by bluebird bio. Targets B-cell maturation antigen.
B cells.
Together with T cells, a lymphocyte that is a mainstay of the adaptive immune system, mediating the humoral response involving antibodies.
BPDCN (blastic plasmacytoid dendritic cell neoplasm).
Formerly natural killer cell leukemia/lymphoma. Form of AML, usually with features of lymphoma and leukemia. No established first-line treatment. No current treatments result in prolonged remission.
CD3-zeta (CD3ζ).
A component of T-cell receptors (TCR) that is nearly always present. In CAR T cells, CD3 ITAMs are a very commonly employed module for signal transduction, in conjunction with one or more co-stimulatory signaling modules.
Expressed on healthy and cancerous B cells alike. Acts a co-receptor with CD 21 and CD81. Targeted by numerous investigational CAR T cells.
Expressed on B cells. Facilitates B-cell development and differentiation. Targeted by rituximab (Rituxan).
Expressed on most B-cell malignancies, including ALL cancer cells that have lost CD19. Target of Juno’s JCAR018.
Co-stimulatory molecule used to enhance signaling power of CAR T cells.
Also known as IL-3Rα, as it is the IL-3 receptor α chain. Expressed on bone marrow stem cells, granulocytes, monocytes, megakaryocytes. Also expressed on malignant cells in AML and BPDCN. Target of UCART123.
Also known as 4-1BB. Co-stimulatory molecule whose signaling domain has been used to enhance the signaling power and clinical effect of CAR T cells. Component of CART19 T cells developed by June and colleagues at University of Pennsylvania.
Also known as L1-CAM. Cell-surface adhesion molecule important for normal nervous system development but overexpressed in neuroblastoma.
CLL (chronic lymphocytic leukemia).
Cancer cells in CLL are called small lymphocytes, found in blood and bone marrow. For 2017, ACS estimates 20,110 new cases and 4,660 deaths from CLL in the United States.
Inhibitory receptor expressed by T cells; binding of CTLA-4 inhibits T-cell activation.
CRS (cytokine release syndrome).
Most serious complication of CAR T-cell therapy. Also seen with other cancer therapies involving T cells. Syndrome may include high fever, unstable hypotension, respiratory failure, myalgias. Severe CRS can be treated with tocilizumab (Actemra).
CTL019 (tisagenlecleucel-T; Novartis).
CAR T-cell therapy developed at University of Pennsylvania. Targets CD19, a cell-surface molecule expressed on malignant B cells and normal B cells. In March 2017, the FDA granted CTL019 priority review for treatment of pediatric and young adult patients with relapsed/refractory B-cell ALL.
durvalumab (MEDI4736).
Investigational monoclonal antibody that blocks PD–L1 binding to PD-1 and CD80, thereby preventing PD–L1-mediated suppression of T-cell activation.
Rare tumor arising from nerve tissues in children. Usually less aggressive than neuroblastoma.
Cytokine produced by some T cells and natural killer cells. Activates macrophages. Produced at high levels in early days following CAR T-cell infusion. May help predict patients at high risk of CRS.
IL-1RA (interleukin-1 receptor antagonist).
Antagonist of function of interleukin 1 (IL-1), which promotes T-cell activation. Could serve as biomarker predicting risk of CRS.
IL-6 (interleukin 6).
Cytokine central to development and progression of inflammatory diseases, cardiovascular disease, and cancer.
IL-13 (interleukin 13).
Produced by T cells, and at high levels in early days following CAR T-cell infusion. May help predict patients at high risk of CRS.
ITAM (immunoreceptor tyrosine-based activation motif).
Intracellular portion of T-cell receptors essential for signaling, found in various CD3 chains. CD3ζ ITAMs are used in CAR T cells.
Investigational autologous CAR T-cell product targeting CD19 whose development was halted by Juno Therapeutics in March 2017 after 5 deaths from cerebral edema in phase 2 trial, enrolling patients with relapsed/refractory ALL.
Investigational autologous CAR T-cell product targeting CD19 being developed by Juno Therapeutics. Has different construct from JCAR015, such as 1:1 ratio of CD8+:CD4+ CAR T cells (vs CD3+ enriched peripheral blood mono­nuclear cells), CD28 co-stimulatory domain (vs CD137). Also incorporates ablative technology (“suicide switch”), truncated form of epidermal growth factor receptor (EGFRt) that can be targeted with cetuximab (Erbitux) if rapid killing of CAR T cells is required.
Juno’s investigational CAR T-cell product targeting CD22. CD22 is present on most B-cell malignancies but also persists on cancerous B cells that have lost CD19.
Juno’s investigational “armored” CAR T-cell product targeting MUC-16, a protein overexpressed in about 70% of ovarian cancers but not found on surface of normal ovary cells. Originally developed by Memorial Sloan Kettering Cancer Center.
Juno’s investigational CAR T-cell product targeting ROR-1, expressed on all CLL and MCL cells and in subsets of ALL and several solid tumors. Originally developed by Fred Hutchinson Cancer Research Center.
Kite’s axicabtagene.
Any white blood cell.
Class of white blood cells bearing variable receptors for antigens on their surface. The two main types are T cells and B cells.
MCL (mantle cell lymphoma).
Represents about 5% of lymphomas. Most common in men (early 60s). Often advanced by time of diagnosis. Originates in lymphocyte in mantle zone of lymph node.
MHC (major histocompatibility complex).
MHC class I molecules are cell-surface molecules that present intracellular antigenic peptides (fragments of pathogens that have entered the cell, such as viruses) to T cells bearing CD8. MHC class II molecules present T cells bearing CD4 with antigenic peptides that are fragments of extracellular pathogens that have been brought into the cell.
MIP-1α (macrophage inflammatory protein 1α).
A proinflammatory chemokine. Expressed at high levels during first few days after CAR T-cell infusion; may help predict patients at high risk of cytokine release syndrome.
MM (multiple myeloma).
Second-most prevalent hematopoietic malignancy. Results in excessive numbers of plasma cells in bone marrow, osteolytic bone lesions. Disease recurrence is common despite advances in treatment (5-year relative survival rate now 50%, vs 25% in 1977). ACS predicts 30,280 new cases (male, 58%) and 12,590 deaths (male, 52%) from MM in 2017.
Cancer originating in neuroblasts of sympathetic nervous system. About a third begin in nerve-like cells in medulla of adrenal glands and about a fourth in the abdominal ganglia. Nearly always occurs in infants and children aged <10 years. Most common cancer in infants.
NHL (non-Hodgkin lymphoma).
Seventh-leading cause of new cancer cases in US, representing about 4% of all cancers. Nearly always originates in B lymphocytes, found in lymph nodes and other lymphoid tissues (spleen, thymus, adenoids & tonsils, digestive tract, bone marrow). For 2017, ACS projects 72,480 new diagnoses and 20,140 deaths the United States.
PD-1 (programmed death-1).
Inhibitory receptor specifically expressed on activated T cells. Its signaling domain is being studied as a component in a novel approach to avoiding off-target immunotherapy responses. See also CTLA-4.
PD–L1 (programmed death ligand-1).
Receptor that binds to inhibitory receptor PD-1. Upregulated by inflammatory cytokines. Inhibition of PD–L1 may enhance effectiveness of T cells attacking cancer cells.
PMBCL (primary mediastinal B-cell lymphoma).
Subtype of DLBCL, representing 2% of all lymphomas. Named for site of origin (mediastinum, behind sternum). Most common in young women (30s).
Protein overexpressed on many cancer cells, including all B-cell CLL and MCL cells and a subset of NSCLC, TNBC, pancreatic cancer, prostate cancer, and ALL. Target of JCAR24.
scFv (single-chain variable fragment).
Extracellular module of chimeric antigen receptor that lets it bind a specific antigen expressed on the surface of a cell). Upon binding to the scFV, intracellular signaling domains within the CAR T cell are triggered.
sgp130 (soluble glycoprotein 130).
Inhibitor of trans IL-6 signaling. High levels of sgp130 have been found in patients within a few days of CAR T-cell infusion. May be helpful in predicting which patients are at high risk of CRS.
T cells (T lymphocytes).
Together with B cells, a mainstay of the adaptive immune system. T cells originate in bone marrow and mature in thymus, from which they get their name.
TCR (T-cell receptor, T-cell antigen receptor).
Cell-surface receptor for antigen. Some TCRs have two variable chains, α (TCRα) and β (TCRβ), and T cells with this TCR thus are known as α:β T cells. Other TCRs have different variable chains, γ and δ. In either TCR, the constant portion, which executes the signaling function of the receptor, consists of CD3 and ζ proteins. Engineered TCRs can recognize a specific MHC/peptide combination of interest (e.g., cancer-associated proteins) and act like the patient’s T cells upon re-infusion, resulting in lysis of tumor cells.
TNBC (triple-negative breast cancer).
Breast cancer that is estrogen-receptor (ER) negative (≤10%), progesterone-receptor (PR) negative (≤10%), and human epidermal growth factor-receptor 2 (HER2) negative. Metastatic TNBC is target of JCAR20.
tocilizumab (Actemra).
IL-6 receptor antagonist indicated for treatment of rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis. Used off-label as first-line treatment for cytokine release syndrome (CRS).
Allogeneic CAR T-cell product targeting CD19. Being co­developed by Servier (Suresnes, France) and Pfizer. In 2015 Servier gained exclusive rights to UCART19 from Cellectis (France). Pfizer acquired a minority stake in Cellectis in 2014 and is working with Servier to advance UCART19.
Allogeneic CAR T-cell product (Cellectis) targeting CD123. Expected to begin phase 1 trials in AML and BPDCN in 2017.

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