© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999

10.4.1.2 Phagocytic Flagging

Target cells may be flagged with biochemical substances capable of triggering a reaction by the body's natural defensive or scavenging systems. For example, novel recognition molecules are expressed on the surface of apoptotic cells. In the case of T lymphocytes, one such molecule is phosphatidylserine, a lipid that is normally restricted to the inner side of the plasma membrane (Section 8.5.3.2) but, after the induction of apoptosis, appears on the outside.²¹¹⁷ Cells bearing this novel surface molecule are then capable of being recognized and removed by phagocytic cells. Seeding the outer wall of a target cell with phosphatidylserine or other molecules with similar action could activate phagocytic behavior by macrophages which had mistakenly identified the target cell as apoptotic. Loading the target cell membrane surface with B7 costimulator molecules permits T-cell recognition, allowing an immunologic response¹⁵⁵⁶ via what has been termed the immunological synapse.^{2930,2931,3453} This tagging operation should work well against cells which have an apoptotic response which can be triggered by cytotoxic T cells -- such as human cancer cells and cysts.

Aside from false apoptosis, removal or destruction of cell-surface MHC class I receptors might convince the immune system that the target cell was not native (e.g., "self"), making the target susceptible to attack by natural killer NK lymphocytes.²¹³⁰ (Macrophages should be able to engulf a eukaryotic cell, as they are large enough to absorb protozoa.⁵³¹) Alternatively, the target cell's surface would be salted with a non-self antigen-containing MHC Class I molecule, or with self MHC Class I molecules with foreign peptide attached (particularly one for which the patient has already been vaccinated), with the expectation that the cell would mistakenly be identified as foreign, and thus be phagocytosed. Other methods of engineering chemical reactivity by cell surface remodeling²¹²⁷ are readily envisioned, such as flagging with lymphokines or oligohistidine-tagged fusion proteins.²²⁷⁴ But the best approach may be to seed the target cell with antigens for which the patient already has a high titer of circulating antibodies, which then will bind to the antigens and attract the immune system. Antibodies occur in higher concentrations than B/T cells and therefore would presumably trigger a faster response. As a general rule, cells with bad MHC molecules are targeted for apoptosis, while cells with antibodies attached are targeted for phagocytosis.

Last updated on 24 February 2003