CD4-Pseudomonas Exotoxin: A Strategy for AIDS Therapy Based on Selective Killing of HIV-Infected Cells
The receptor for human immunodeficiency virus (HIV) is CD4, a 55 kD glycoprotein expressed on the surface of certain human lymphoid and monocytic cell types1. The finding2–7 that recombinant soluble forms of CD4 retain the capacity for high affinity binding to gp120 (the external subunit of the HIV envelope glycoprotein) has suggested potential therapeutic uses of CD4 derivatives. For example, soluble truncated forms of CD4 (sCD4) are able to neutralize HIV infectivity in vitro 2–6,suggesting they may have specific anti-viral activity in HIV-infected individuals. Several “second-generation” applications of this neutralizing concept are under development, including attachment of the CD4 to immunoglobulin constant region sequences8–12, or presentation of the CD4 in association with erythrocytes13. These modifications provide the advantages of increased plasma half-life compared to sCD4, and possibly enhanced efficiency of neutralization due to multivalency.
KeywordsHuman Immunodeficiency Virus Human Immunodeficiency Virus Infection Infected Cell Line Selective Killing Human Immunodeficiency Virus Spread
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