Over two hundred thousand Americans are diagnosed each year with potentially deadly locally advanced cancers, representing a huge potential for improving treatment, as well as a multi-billion dollar undeveloped local-regional chemotherapy market.
For locally advanced cancers HylaPharm‘s patent-protected anti-cancer drug technology appears to be safer and more effective based on several mouse studies. In dogs intra-tumoral HylaPlat delivers over 100x more drug to tumors and draining nodes, allowing for lower overall dosing. Our drug has worked safely and successfully treated a pet dog with a large cancer in his mouth (see photos at our Benefits page). Kansas BioScience Authority has funded upcoming FDA IND-enabling animal trials. The platform may also be applicable for systemic chemotherapy with a better therapeutic index; experiments are ongoing.
Three key attributes are:
- Size: The 20nm size allows for penetration into tumors and retention in adjacent lymph nodes where cancers metastasize.
- Drug: This platform allows packaging of systemically toxic chemotherapeutics into a nanoparticle that can be locally delivered with minimal local toxicity. Cisplatin, doxorubicin, and docetaxol have been tested with encouraging results. The platform is generalizable to a broader list of agents over a wide molecular weight range (up to small antibodies).
- Hyaluronan conjugation allows local injection directly into the tumor, and also targets a key cancer receptor, CD44. Higher CD44 expression is associated with aggression and with so-called “cancer stem cell” status.
Transmission electron microscopy picture showing HA and cisplatin condense into a <100 nm particle.
To date, 17 peer-reviewed publications have been based on the nanoconjugate technology. HylaPharm’s technology has shown success in xenograft models of locally advanced / regionally metastatic melanoma, head and neck cancer, and breast cancer, as well as lymphoma. It has been used with various anticancer drugs including cisplatin, doxorubicin, and multiple taxanes. This technology also has been applied to anti-infective agents and for locoregional immune suppression. Some highlights are below.
Drug travels from injection site into local lymph nodes
|HylaPharm nanoconjugate is injected into tumor, after which it drains into local lymph nodes where cancer cells generally spread first.||HylaPharm coated imaging agent injected into mouse footpad, traveling to lymph nodes.|
Efficacy in Murine Xenograft of human head and neck squamous cell carcinoma (MDA1986)
Animals received 3 doses (1/week) once tumors researched 50 mm2. All drugs/controls (n=6-8/group) dosed at 3 mg/kg on a platinum basis.
Efficacy in Murine Xenograft of breast cancer (locoregional with lymphatic mets, MDA-MB-468LN)Animals received 3 doses (1/wk) once tumors researched 100 mm2. All drugs/controls (n=6-8/group) dosed at 2 mg/kg on a doxorubicin basis.Canine Pharmacokinetics 96 hours after a single 10 mg/kg injection of HylaPlatCanines presented with spontaneous leg sarcomas. After 96 hrs, legs were amputated and drug levels in the tumor and sentinel lymph node were determined by ICP-MS. I.v. data were taken from historic files at Colorado State University.
|Cmax, ng/mL||81.6 ± 40.4||1793.8 ± 359|
|t1/2, hrs||51.2 ± 29.1||0.49 ± 0.03|
|AUC0-inf, ng·hr/mL||3562.1 ± 2031.1||1240 ± 200|
|Tumor, ng/g at 96 hrs||5650.0 (3324.5 – 8228.8)||–|
|Lymph node draining tumor, ng/g at 96 hrs||2485.0 (129.5 – 6066.0)||5|
Data from Dr. Deanna Worley, DVM, Colorado State University. Am. J. Vet. Res. 73(12):1969-76 (2012).