Table 2.
Some examples of strategies for modification of Ad tropism.
| Ad vector | Tropism altering modification | Basis of altered tropism | Cell type | Response | References |
|---|---|---|---|---|---|
| Ad5-pk7 | Polylysine (pK7) motif on HAd5 knob | Enhanced transduction of cancer cells with high surface HSPGs | Human glioma xenografts in mouse model | Higher transduction and marker gene expression | Zheng et al. (2007) |
| Ad5/3-RGD | HAd5 with HAd3 knob containing RGD domain | Enhanced transduction of cancer cells with high integrin expression | Human glioma xenografts in mouse model | 1000-fold increased infectivity | Ulasov et al. (2006) |
| Ad5Luc1-CK1 | HAd5 containing CAV-1 knob | Enhanced CAV knob-mediated, CAR-independent vector transduction | Ovarian cancer cell lines/ovarian cancer patients | Superior transduction of cancer cells | Stoff-Khalili et al. (2005) |
| Primary tissue slice samples | |||||
| CAV-2 (canine Ad) | Nonhuman Ad with alternate tropism | Use of alternate/distinct receptors | In vivo mouse respiratory tract | Efficient transduction of respiratory epithelia | Keriel et al. (2006) |
| Ex vivo human pulmonary epithelia | Escape HAd5 immunity | ||||
| Low inflammation | |||||
| HAd5 | mEGF-polymer coating | Selective transduction of EGFR rich cancer cells | Peritoneal xenograft model of human ovarian cancer in mouse model | Restricted vector tropism and toxicity and enhanced antitumor efficacy | Morrison et al. (2008) |
| HAd5 | Bispecific antibody (Ab) targeting HAd fiber knob and human endoglin | Bispecific Ab bridge Ad to vascular endoglin upregulated in angiogenic areas of tumors | Primary endothelial cells and HUVEC cell line | Enhanced, selective and CAR-independent transduction of HUVEC | Nettelbeck et al. (2001) |
Abbreviations: CAV: canine adenovirus; mEGF: murine epidermal growth factor; EGFR: EGF receptor; HUVEC: human umbilical vein endothelial cells; HSPG: heparan sulfate proteoglycans; Ab: antibody.