The effects of an immunomodulatory LFA3-IgG1 fusion protein on nonhuman primates.
LFA3TIP, a fusion protein comprised of the first extracellular domain of LFA-3 fused to the hinge, CH2 and CH3 domains of human IgG1, inhibits proliferation of human T cells in vitro. LFA3TIP also inhibits responses of human CD2 transgenic mice by rapidly and totally depleting peripheral T cells. These effects require binding of the LFA-3 and CH2 domains of LFA3TIP to CD2+ T cells and Fc gamma R+ accessory cells, respectively. As CD2 is well conserved in primate species, we evaluated the effects of LFA3TIP in nonhuman primates. We report in vitro results leading to the selection of the baboon as a model for analysis of LFA3TIP, and in vivo effects of single and multidose regimens of LFA3TIP administration. This is the first report of the in vivo administration of an immunomodulatory fusion protein to primates. LFA3TIP is shown to mediate effects on primate T lymphocytes without apparent related toxicities or immunogenicity. Results are discussed in context of potential mechanisms of LFA3TIP immunotherapy.
Chisholm
P L
PL
Biogen, Cambridge, MA 02142, USA.
Williams
C A
CA
Jones
W E
WE
Majeau
G R
GR
Oleson
F B
FB
Burrus-Fischer
B
B
Meier
W
W
Hochman
P S
PS
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D018801:CD2 Antigens / Q000378:metabolism; D018968:CD58 Antigens / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005260:Female; D007074:Immunoglobulin G / Q000737:chemistry; D007166:Immunosuppressive Agents; D007958:Leukocyte Count / Q000187:drug effects; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008252:Macaca fascicularis; D008253:Macaca mulatta; D010215:Papio; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D018801:CD2 Antigens; D018968:CD58 Antigens; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins