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Immuno-adjuvant PDT treatment of metastatic tumors

Inactive Publication Date: 2002-02-21
QLT INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The use of this adjuvant may result in serious side effects including organ injury via granuloma formation and autoimmune disease, and its use is restricted even in experimental animals.
Incomplete Freund's Adjuvant (IFA), which lacks the mycobacterial component of CFA, is less toxic but does not enhance cell-mediated immunity.
Thus experimental combinations of immuno-adjuvants and PDT were attempted with little predictability as to actual efficacy and general application.

Method used

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  • Immuno-adjuvant PDT treatment of metastatic tumors
  • Immuno-adjuvant PDT treatment of metastatic tumors
  • Immuno-adjuvant PDT treatment of metastatic tumors

Examples

Experimental program
Comparison scheme
Effect test

example 1

Sample Animals and Tumor Model

[0150] Male, C57BL / 6 mice were obtained from Charles River Canada (Montreal, QC) at 6 to 8 weeks of age. The B16-F0 and B16-F1 melanoma cell lines were obtained from the American Type Tissue Collection (Manassas, Va.) and grown as cell cultures in Dulbecco's Modified Eagle Medium (DMEM) (Gibco) supplemented with 10% fetal bovine serum (Sigma). The cells adhered to tissue culture plates, were removed for passage with 0.25% trypsin with 1.0 mM ethylenediaminetetraacetic acid (EDTA) (Gibco), and were cryo-preserved in liquid nitrogen in DMEM plus 40% FBS and 10% DMSO. Mice were injected with 5.times.10.sup.5 tumor cells in a total volume of 50 .mu.L subcutaneously into the shaved, right flank. The tumor size was monitored daily by measuring the diameter with vernier calipers and were treated when the tumors reached approximately 5 mm in diameter. In initial experiments, the B16-F0 and B16-F1 were characterized with respect to in vivo growth rates and metas...

example 2

Sample Immuno-Adjuvant PDT

[0151] PDT treatment of mice bearing the B 16-F1 tumor was performed as previously described for the M1 rhabdomyosarcoma mouse tumor (Richter et al., 1987; Richter et al., 1988; Richter et al., 1991). Each mouse was weighed, warmed under infrared light for less than 5 min to dilate the blood vessels, restrained, and injected intravenously (tail vein) with Verteporfin at a concentration of 1.0 mg / kg body weight using a 28G needle. Thirty minutes later, animals were restrained and half of the animals were injected intratumorally with 50 .mu.L of Titermax adjuvant (Sigma) prepared as an emulsion with sterile phosphate buffered saline (PBS) according to the manufacturers specifications. Animals were then exposed to a light dose of 100 J / cm.sup.2 in a circular area encompassing the tumor of 1 cm diameter at 688 nm wavelength. The power density was 70 mW / cm.sup.2 and resulted in treatment times of 24 min per animal. Following treatment, animals were monitored dai...

example 3

Sample Experimental Metastases

[0152] Pulmonary metastases were generated by intravenous injection of tumor cells according to standard methods described by several groups (Chapoval et al., 1998; Lin et al., 1998; Volpert et al., 1998; Wang et al., 1998). Pulmonary metastases were initiated in each group of treated mice, as described in Example 2 above, when the tumor was considered cured. This involved multiple treatments in some of the mice and all test animals were injected intravenously with tumor cells on the same day. Following PDT or immuno-adjuvant PDT animals were monitored for tumor response and if positive, Test (PDT and immuno-adjuvant PDT) and Control (naive) animals were injected with 5.times.10.sup.5 tumor cells in 250 .mu.l PBS via the lateral tail vein. The animals were monitored for tumor recurrence and general health for 14 days after which the animals were sacrificed using CO.sub.2 inhalation and their lungs removed. Pulmonary metastases were clearly visible as bl...

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Abstract

Immuno-adjuvant photodynamic therapy to treat and prevent metastatic cancer is effected using photosensitizers in combination with immuno-adjuvants to destroy metastatic tumor cells.

Description

[0001] This application is a continuation-in-part application of U.S. patent application Ser. No. 09 / 556,833, filed Apr. 21, 2000, which claims benefit of priority from U.S. Provisional Application 60 / 130,519, filed Apr. 23, 1999, both of which are hereby incorporated by reference as if fully set forth.[0002] The invention relates to the use of photodynamic therapy (PDT) treatment in combination with immuno-adjuvants to treat metastatic tumors. This provides a novel treatment modality termed photodynamic vaccination, or PDV. The PDV may be conducted with any photosensitizer, but combinations comprising a benzoporphyrin derivative (BPD) are preferred for such PDV treatment.DESCRIPTION OF THE RELATED ART[0003] This invention relates to metastatic cancer. The metastatic process, which results in the growth of secondary tumors at sites distal to the primary tumor, is the cause of death in most cancers (Poste and Fidler, 1980). Although most patients with newly diagnosed solid tumors are...

Claims

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Application Information

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IPC IPC(8): A61K41/00
CPCA61K41/0057A61K41/0071
Inventor CURRY, PATRICK MARKRICHTER, ANNA M.LEVY, JULIA G.HUNT, DAVID W.C.
Owner QLT INC
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