Specific thermal ablation of tumor cells using single-walled carbon nanotubes targeted by covalently-coupled monoclonal antibodies.
CD22 is broadly expressed on human B cell lymphomas. Monoclonal anti-CD22 antibodies alone, or coupled to toxins, have been used to selectively target these tumors both in SCID mice with xenografted human lymphoma cell lines and in patients with B cell lymphomas. Single-walled carbon nanotubes (CNTs) attached to antibodies or peptides represent another approach to targeting cancer cells. CNTs convert absorbed near-infrared (NIR) light to heat, which can thermally ablate cells that have bound the CNTs. We have previously demonstrated that monoclonal antibodies (MAbs) noncovalently coupled to CNTs can specifically target and kill cells in vitro. Here, we describe the preparation of conjugates in which the MAbs are covalently conjugated to the CNTs. The specificity of both the binding and NIR-mediated killing of the tumor cells by the MAb-CNTs is demonstrated by using CD22+CD25- Daudi cells, CD22-CD25+ phytohemagglutinin-activated normal human peripheral blood mononuclear cells, and CNTs covalently modified with either anti-CD22 or anti-CD25. We further demonstrate that the stability and specificity of the MAb-CNT conjugates are preserved following incubation in either sodium dodecyl sulfate or mouse serum, indicating that they should be stable for in vivo use.
Marches
Radu
R
The Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-8576, USA.
Chakravarty
Pavitra
P
Musselman
Inga H
IH
Bajaj
Pooja
P
Azad
Robert N
RN
Pantano
Paul
P
Draper
Rockford K
RK
Vitetta
Ellen S
ES
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006358:Hot Temperature; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000627:therapeutic use*; D007259:Infrared Rays; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000528:radiation effects; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D037742:Nanotubes, Carbon; D010835:Phytohemagglutinins / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D037742:Nanotubes, Carbon; D010835:Phytohemagglutinins; D051918:Sialic Acid Binding Ig-like Lectin 2