Marches Radu, Chakravarty Pavitra, Musselman Inga H, Bajaj Pooja, Azad Robert N, Pantano Paul, Draper Rockford K, Vitetta Ellen S
The Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-8576, USA.
Int J Cancer. 2009 Dec 15;125(12):2970-7. doi: 10.1002/ijc.24659.
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.
CD22在人类B细胞淋巴瘤中广泛表达。单独的单克隆抗CD22抗体或与毒素偶联的单克隆抗CD22抗体，已被用于在移植了人类淋巴瘤细胞系的SCID小鼠以及B细胞淋巴瘤患者体内选择性地靶向这些肿瘤。附着有抗体或肽的单壁碳纳米管（CNT）代表了另一种靶向癌细胞的方法。CNT可将吸收的近红外（NIR）光转化为热量，从而热消融结合了CNT的细胞。我们之前已经证明，非共价偶联到CNT的单克隆抗体（MAb）在体外能够特异性地靶向并杀死细胞。在此，我们描述了MAb与CNT共价偶联的缀合物的制备方法。通过使用CD22+CD25-的Daudi细胞、CD22-CD25+的植物血凝素激活的正常人外周血单个核细胞，以及用抗CD22或抗CD25共价修饰的CNT，证明了MAb-CNT对肿瘤细胞的结合特异性和近红外介导的杀伤作用。我们进一步证明，在十二烷基硫酸钠或小鼠血清中孵育后，MAb-CNT缀合物的稳定性和特异性得以保留，这表明它们在体内使用时应该是稳定的。
