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| Content Provider | Springer Nature Link |
|---|---|
| Author | Yang, Qin Larsen, Stine K. Mi, Zhibao Robbins, Paul D. Basse, Per H. |
| Copyright Year | 2008 |
| Abstract | Using the approach of peptide transduction domain (PTD)-mediated loading of interleukin-2(IL-2)-activated natural killer (A-NK) cells, tumor-seeking lymphocytes, with prodrug-activating enzymes, we primarily aim to generate a cytotoxic drug selectively within tumors and minimize damage to normal tissues. A-NK cells are able to accumulate selectively at tumor sites. While these cells by themselves possess significant antitumor effect in vivo, we suggest that they can also serve as Trojan horses, by bringing anticancer agents, such as prodrug-activating enzymes, selectively to tumors. We have successfully demonstrated in a mouse model that A-NK cells can be rapidly loaded with prodrug-activating enzymes, such as alkaline phosphatase (AP) and beta-galactosidase (beta-gal), in vitro using enzyme-conjugated peptide PTD5. Upon adoptive transfer into lung-tumor-bearing animals, the loaded A-NK cells are able to bring their cargo of the prodrug-activating enzymes selectively to pulmonary metastases. The targeting of the AP to the tumor tissues is highly specific, since more than a fivefold higher concentration of AP was found in the tumor tissues compared to the surrounding normal lung tissue at 24 h after injection. The approach of transporting prodrug-activating enzymes selectively into tumors clearly shows potential for future targeted chemotherapy. Ongoing studies in our laboratory are evaluating the antitumor efficacy of cellular-dependent enzyme prodrug therapy. |
| Starting Page | 614 |
| Ending Page | 621 |
| Page Count | 8 |
| File Format | |
| ISSN | 12341234 |
| Journal | The AAPS Journal |
| Volume Number | 10 |
| Issue Number | 4 |
| e-ISSN | 15507416 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2008-12-23 |
| Publisher Institution | American Association of Pharmaceutical Scientists |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | activated natural killer cells delivery metastases in vivo prodrug enzymes protein transduction domain Pharmacy Biotechnology Biochemistry Pharmacology/Toxicology |
| Content Type | Text |
| Resource Type | Article |
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