Biodistribution of charged F(ab')2 photoimmunoconjugates in a xenograft model of ovarian cancer

Duska, Linda R.; Hamblin, Michael R.; Bamberg, M.; Hasan, Tayyaba

doi:10.1038/bjc.1997.149

Cited by 50 publications

(53 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, these conjugate preparations often contained significant amounts of impurities. A more refined method for conjugation to polymeric cationic and anionic carriers was later developed by Hamblin et al (1996) and was used successfully in vitro and in vivo (Duska et al, 1997). Within these studies, a chlorin e6-NHS ester is used without purification prior to attachment to the macromolecule.…”

Section: Discussionmentioning

confidence: 99%

The development and characterisation of porphyrin isothiocyanate–monoclonal antibody conjugates for photoimmunotherapy

et al. 2005

View full text Add to dashboard Cite

A promising approach to increase the specificity of photosensitisers used in photodynamic therapy has been through conjugation to monoclonal antibodies (MAb) directed against tumour-associated antigens. Many of the conjugations performed to date have relied on the activated ester method, which can lead to impure conjugate preparations and antibody crosslinking. Here, we report the development of photosensitiser -MAb conjugates utilising two porphyrin isothiocyanates. The presence of a single reactive isothiocyanate allowed facile conjugation to MAb FSP 77 and 17.1A directed against internalising antigens, and MAb 35A7 that binds to a non-internalising antigen. The photosensitiser -MAb conjugates substituted with 1 -3 mol of photosensitiser were characterised in vitro. No appreciable loss of immunoreactivity was observed and binding specificity was comparable to that of the unconjugated MAb. Substitution with photosensitiser had a minimal effect on antibody biodistribution in vivo for the majority of the conjugates, although a decreased serum half-life was observed using a cationic photosensitiser at the higher loading ratios. Tumour-to-normal tissue ratios as high as 33.5 were observed using MAb 35A7 conjugates. The internalising conjugate showed a higher level of phototoxicity as compared with the non-internalising reagent, using a cell line engineered to express both target antigens. These data demonstrate the applicability of the isothiocyanate group for the development of high-quality conjugates, and the use of internalising MAb to significantly increase the photodynamic efficiency of conjugates during photoimmunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

The development and characterisation of porphyrin isothiocyanate–monoclonal antibody conjugates for photoimmunotherapy

et al. 2005

View full text Add to dashboard Cite

show abstract

“…These targeting species include monoclonal antibodies (Duska et al, 1997), lipoproteins (Hamblin and Newman, 1994b), microspheres (Bachor et al, 1991), liposomes (Cuomo et al, 1990) and polymers (Krinick et al, 1994). The latter may be either natural polymers such as dextran (Rakestraw et al, 1990) and polyamino-acids (Goff et al, 1991;Soukos et al, 1997) or synthetic polymers such as N-(2-hydroxypropyl)-methacrylamide (Seymour et al, 1987) and polyvinyl alcohol (Davis et al, 1993).…”

mentioning

confidence: 99%

In vivo fluorescence imaging of the transport of charged chlorin e6 conjugates in a rat orthotopic prostate tumour

et al. 1999

Self Cite

View full text Add to dashboard Cite

Summary Polymeric drug conjugates are used in cancer therapy and, varying their molecular size and charge, will affect their in vivo transport and extravasation in tumours. Partitioning between tumour vasculature and tumour tissue will be of particular significance in the case of photosensitizer conjugates used in photodynamic therapy, where this partitioning can lead to different therapeutic effects. Poly-l-lysine chlorin e6 conjugates (derived from polymers of average M r 5000 and 25 000) were prepared both in a cationic state and by poly-succinylation in an anionic state. A fluorescence scanning laser microscope was used to follow the pharmacokinetics of these conjugates in vivo in an orthotopic rat prostate cancer model obtained with MatLyLu cells. Fluorescence was excited with the 454-528 nm group of lines of an argon laser and a 570 nm long pass filter used to isolate the emission. Results showed that the conjugates initially bound to the walls of the vasculature, before extravasating into the tissue, and eventually increasing in fluorescence. The anionic conjugates produced tissue fluorescence faster than the cationic ones, and surprisingly, the larger M r conjugates produced tissue fluorescence faster than the smaller ones with the same charge. These results are consistent with differences in aggregation state between conjugates.

show abstract

“…In the NIH-OVCAR-5 human ovarian tumor xenograft, the i.p.-administered positively charged immunoconjugate delivered much higher amounts of chlorin e6 to the tumor tissue than the negatively charged immunoconjugate and a nontargeted immunoconjugate prepared with a nonspecific IgG and free chlorin e6. 78 Multiple intraperitoneal PDT performed at 3 hours after photosensitizer administration (i.p.) in the same tumor model demonstrated that tumor-bearing animals tolerated the repeated PDT treatments well, and tumor responses (residual tumor weight and animal survival time) to the positively charged conjugate were much better than responses to the negatively charged or free chlorin e6.…”

Section: Tumor Surface Proteins or Peptidesmentioning

confidence: 99%

Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

Chen¹,

He²

2006

View full text Add to dashboard Cite

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERUniversity of the Sciences in Philadelphia Philadelphia, PA 19104 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel CommandFort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTESOriginal contains colored plates: ALL DTIC reproductions will be in black and white.14. ABSTRACT An obstacle for successful drug therapy for cancer is the existence of drug delivery barriers, which causes insufficient drug delivery to the tumor tissue. Because of inadequate drug delivery to the tumor tissue, the drug dose has to be increased, which leads to normal tissue toxicity. This delivery problem not only limits the clinical application of existing chemotherapeutics, but also decreases the effectiveness of many new drugs under development for prostate cancer. We found that vascular targeting photodynamic therapy (PDT), a modality involving the combination of a photosensitizer and laser light, is able to disrupt tumor vascular barrier, a significant hindrance to drug delivery. Therefore, tumor accumulation of circulating molecules is significantly enhanced, as demonstrated by intravital fluorescence microscopy and whole-body fluorescence imaging techniques. Immunofluorescence staining of endothelial cytoskeleton structure further indicates microtubule depolymerization, stress actin fiber formation and intercellular gap formation. Based on these results, we propose to use this laser-based therapy to enhance anticancer drug effectiveness. PDT is currently in worldwide multicenter clinical trials for the localized prostate cancer therapy. The available results indicate that PDT employing advanced laser fiber technology and sophisticated light dosimetry is able to treat localized prostate cancer in an effective and safe way. The combination of photosensitization with current chemotherapy or other new drug therapies will greatly improve clinical...

show abstract

Biodistribution of charged F(ab')2 photoimmunoconjugates in a xenograft model of ovarian cancer

Cited by 50 publications

References 21 publications

The development and characterisation of porphyrin isothiocyanate–monoclonal antibody conjugates for photoimmunotherapy

The development and characterisation of porphyrin isothiocyanate–monoclonal antibody conjugates for photoimmunotherapy

In vivo fluorescence imaging of the transport of charged chlorin e6 conjugates in a rat orthotopic prostate tumour

Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

Contact Info

Product

Resources

About