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Results: 4

1.
Figure 1

Figure 1. Components of the innate and adaptive immune system. From: Immunotherapy of Childhood Cancer: From Biologic Understanding to Clinical Application.

Adapted from: Mackall CL, Sondel PM: Tumor immunology and pediatric cancer. In Pizzo, P.A. and Poplack, D.G. (eds) Principles and Practice of Pediatric Oncology, 6th edition. Philadelphia, PA, Lippincott Raven Publishers, 2009 (in press).6

Alan S. Wayne, et al. Curr Opin Pediatr. ;22(1):2-11.
2.
Figure 2

Figure 2. Structure of immunoglobin and monoclonal antibody fragments. From: Immunotherapy of Childhood Cancer: From Biologic Understanding to Clinical Application.

The immunoglobulin-G (IgG) molecule is composed of two longer (heavy) chains and two shorter (light) chains that are connected by disulfide bonds. The amino acid sequence of the variable (v) ends of each of the four chains determines the specificity of antigen binding. Humanized monoclonal antibody constructs consist predominantly of human amino acid sequences, with the exception of the three hypervariable complementarity-determining regions (CDR), which retain the foreign-specie sequences critical for antigen binding. The CDR domains are indicated by the dark bands at the end of the antigen-binding portion of the molecule.
Fab: Antigen binding fragment; Fc: Crystallizable or complement fixing fragment; Fv: Variable fragment

Alan S. Wayne, et al. Curr Opin Pediatr. ;22(1):2-11.
3.
Figure 3

Figure 3. Pseudomonas-based immunotoxins: structure and mechanism of cytotoxicity Inset:. From: Immunotherapy of Childhood Cancer: From Biologic Understanding to Clinical Application.

Full-length Pseudomonas exotoxin A (PE) protein contains three functional domains that mediate antigen binding, cytosolic translocation, and cytotoxicity. The recombinant anti-CD22 immunotoxin RFB4(dsFv)-PE38 consists of cloned disulfide-stabilized single chain variable fragment (Fv) from the anti-CD22 monoclonal antibody RFB4 and the PE translocation and killing domains (PE38).
Immunotoxin binding to surface CD22 is followed by internalization through endocytosis. Immunotoxin cleavage occurs in the endosome and the C-terminal fragment is transported to the cytosol. ADP ribosylation (ADP-r) inactivates elongation factor-2 (EF2), which inhibits protein synthesis causing cell death.
Adapted from: Wayne AS. Application of immunotherapy in pediatric leukemias. Curr Hematol Malig Reports 2009;4(3):159-166.17

Alan S. Wayne, et al. Curr Opin Pediatr. ;22(1):2-11.
4.
Figure 4

Figure 4. The T cell immune response. From: Immunotherapy of Childhood Cancer: From Biologic Understanding to Clinical Application.

T cells recognize antigen as small peptides derived from the breakdown of intracellular proteins displayed on the surface of antigen presenting cells in the context of major histocompatibility (MHC) antigens. Tumor antigens are cleaved by the proteasome into fragment peptides. The peptides transported by the transporter associated with antigen processing (TAP) into the endoplasmic reticulum, where they are loaded onto MHC molecules that are assembled and transported to the cell surface.
Activation of naïve T cells requires the interaction of an appropriate T cell receptor (TCR) and MHC-presented peptide antigen (Signal #1) and a co-stimulatory signal (Signal #2).
β2M: beta-2 microglobulin
Adapted from: Kong HT, Restifo NP: Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nature Immunol 2002;3:999-1005.12

Alan S. Wayne, et al. Curr Opin Pediatr. ;22(1):2-11.

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