Cytotoxic T cells play an important role in the immune defense mechanism by identifying and eliminating malignant target cells.³

T cells are constantly circulating through blood, lymph, and tissues in search of malignant target cells.² T cells are activated when T-cell receptors bind to antigens on the surface of target cells.⁴

Activated T cells use a variety of mechanisms to eliminate malignant
target cells, inducing the release of cytotoxic components^3,4:

1. After target cell binding, T cells release perforins, which cause cell lysis by forming pores in the membrane of target cells^2-4
2. Cytotoxic serine proteases, or granzymes, are also released from the active T cells and degrade vital cell structures^2,3
3. T cells may also initiate apoptosis via engagement of the Fas ligand^3,4

This immune response can be induced by T cells engaged with target cells at different stages of the cell cycle which may allow for the killing of slowly dividing, stem, or progenitor cells.^5,6 T cell mediated cytotoxicity may help facilitate expansion of a local T-cell population.^2,11

Malignant cells can evade destruction by cytotoxic T cells.^2,7 Mechanisms
of evading the immune system can include:

• Genetic mutations and deletions that impair antigen presentation⁷
• Blockade of cytotoxic T-cell receptor signaling processes that lead
  to cell lysis⁷
• Loss of regulatory control of negative costimulatory signals that
  down-regulate T-cell immune responses⁷
• Secretion of immunosuppressive factors such as TGF-ß, IL-10, PGE₂,
  and sialomucins⁷
  • The release of TGF-beta may result in the inhibition of T cell activation, proliferation, and differentiation⁷

Bispecific T cell Engager (BiTE^®) technology is designed to bind polyclonal cytotoxic T cells and targeted malignant cells^1,2,8

The BiTE^® antibody construct is engineered from two flexibly linked,
single-chain antibodies²:

• One antibody is specific for a selected surface antigen on targeted
  malignant cells²
• The other antibody is specific for CD3—tied to the T-cell receptor complex on the surface of T cells²

BiTE^® represents an innovative area of research
in the evolution of antibody-based immune therapeutics
whose clinical effectiveness is currently being
investigated by Amgen.^2,8