Publications by authors named "Alyson Marin"

4 Publications

  • Page 1 of 1

Submicron particle docetaxel intratumoral injection in combination with anti-mCTLA-4 into 4T1-Luc orthotopic implants reduces primary tumor and metastatic pulmonary lesions.

Med Oncol 2021 Jul 31;38(9):106. Epub 2021 Jul 31.

US Biotest, Inc., 231 Bonetti Drive, Suite 240, San Luis Obispo, CA, USA.

We describe here characterization of the response of local and metastatic disease and immunomodulation following intratumoral (IT) injection of submicron particle docetaxel (SPD) administered alone or in combination with systemic antibody anti-mCTLA-4 (anti-mCTLA-4) in the metastatic 4T1-Luc2-1A4 (4T1) murine breast cancer model. In-life assessments of treatment tolerance, tumor volume (TV), and metastasis were performed (n = 10 animals/group). At study end, immune cell populations in tumor-site tissues and peripheral blood were analyzed using flow cytometry. Signs of distress typical of this aggressive tumor model occurred across all animals except for the combination treated which were asymptomatic and gained weight. TV at study end was significantly reduced in the combination group versus untreated [43% reduced (p < 0.05)] and vehicle controls [54% reduced (p < 0.0001)]. No evidence of thoracic metastasis was found in 40% of combination group animals and thoracic bioluminescence imaging (BLI) was reduced vs. untreated controls (p < 0.01). Significant elevations (p < 0.05) in CD4 + T, CD4 + helper T, Treg, and NKT cells were found in tumor and blood in SPD or combination treatment compared to controls or anti-mCTLA-4. Combination treatment increased tumor-associated CD8 + T cells (p < 0.01), peripheral B cells (p < 0.01), and tumor associated and circulating dendritic cells (DC) (p < 0.05). Tumor-associated NK cells were significantly increased in SPD ± anti-mCTLA-4 treatments (p < 0.01). Myeloid-derived suppressor cells (MDSC) were reduced in bloods in SPD ± anti-mCTLA-4 groups (p < 0.05). These data demonstrate that both SPD and anti-mCTLA-4 produce local anti-tumor effects as well as reductions in metastasis which are significantly enhanced when administered in combination.
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http://dx.doi.org/10.1007/s12032-021-01555-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325653PMC
July 2021

Local administration of submicron particle paclitaxel to solid carcinomas induces direct cytotoxicity and immune-mediated tumoricidal effects without local or systemic toxicity: preclinical and clinical studies.

Drug Deliv Transl Res 2021 Oct 6;11(5):1806-1817. Epub 2020 Nov 6.

US Biotest, Inc. 231 Bonetti Drive, Suite 240, San Luis Obispo, CA, 93401,, USA.

This report describes local administration of submicron particle paclitaxel (SPP) (NanoPac®: ~ 800-nm-sized particles with high relative surface area with each particle containing ~ 2 billion molecules of paclitaxel) in preclinical models and clinical trials evaluating treatment of carcinomas. Paclitaxel is active in the treatment of epithelial solid tumors including ovarian, peritoneal, pancreatic, breast, esophageal, prostate, and non-small cell lung cancer. SPP has been delivered directly to solid tumors, where the particles are retained and continuously release the drug, exposing primary tumors to high, therapeutic levels of paclitaxel for several weeks. As a result, tumor cell death shifts from primarily apoptosis to both apoptosis and necroptosis. Direct local tumoricidal effects of paclitaxel, as well as stimulation of innate and adaptive immune responses, contribute to antineoplastic effects. Local administration of SPP may facilitate tumor response to systemically administered chemotherapy, targeted therapy, or immunotherapy without contributing to systemic toxicity. Results of preclinical and clinical investigations described here suggest that local administration of SPP achieves clinical benefit with negligible toxicity and may complement standard treatments for metastatic disease.
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http://dx.doi.org/10.1007/s13346-020-00868-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421313PMC
October 2021

Phase II study of intraperitoneal submicron particle paclitaxel (SPP) plus IV carboplatin and paclitaxel in patients with epithelial ovarian cancersurgery.

Gynecol Oncol Rep 2020 Nov 28;34:100627. Epub 2020 Aug 28.

US Biotest Inc., 231 Bonetti Dr # 240, San Luis Obispo, CA 93401, USA.

Submicron particles (~800 nm) of paclitaxel (SPP) contain 1-2 billion molecules of pure drug that release tumoricidal levels of paclitaxel over many weeks. This study compared two dose-levels of SPP instilled into the peritoneal cavity (IP) in 200 ml of saline post-cytoreductive surgery. Eligible patients with primary (n = 6) or recurrent (n = 4) epithelial ovarian cancer who underwent complete cytoreductive surgery were enrolled to receive a single instillation of IP SPP followed by standard IV carboplatin and paclitaxel. Endpoints were PFS and evaluation of treatment emergent adverse events. Clinical response was determined by symptoms, physical exams, CT scans, and serum CA-125 measurements. Of the 24 subjects screened, 10 were enrolled and received treatment: seven patients received 100 mg/m and three received 200 mg/m. Seven subjects completed the 12-month follow-up period. Six patients were evaluable due to one subject who had unevaluable scans throughout the follow-up period and was thus excluded from PFS determination. Upon completion of planned chemotherapy post-SPP instillation, the PFS at 6 months was 66% (4/6) and at 12-months 66% (4/6) using RECIST 1.1. One subject had a complete response at the end of IV treatment but died (unrelated to study treatment) before PFS evaluation. There was one case of incision dehiscence and one case of vaginal cuff leakage after surgery. This pilot study supports further evaluation of IP SPP to treat peritoneal carcinomas.
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http://dx.doi.org/10.1016/j.gore.2020.100627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486435PMC
November 2020

Intratumoral submicron particle docetaxel inhibits syngeneic Renca renal cancer growth and increases CD4+, CD8+, and Treg levels in peripheral blood.

Invest New Drugs 2020 10 20;38(5):1618-1626. Epub 2020 Mar 20.

US Biotest, Inc., 231 Bonetti Drive, Suite 240, San Luis Obispo, CA, 93401, USA.

Administration of chemotherapeutics as direct injections into tumors offers increased anti-tumor activity and reduced systemic toxicity. In this study, the Renca syngeneic murine xenograft model of renal cancer was used to evaluate the effects of intratumoral (IT) submicron particle docetaxel (NanoDoce®) on tumor growth and immunomodulation. Tumor volume (TV) was compared to controls, including intravenous (IV) chemotherapy. Flow cytometry of peripheral bloods and tumors was used to evaluate immune cell populations. Groups of animals were inoculated with a second Renca tumor at a site distant from the primary tumor. IT NanoDoce significantly reduced primary TV and reduced the growth rates of untreated secondary tumors. CD4+, CD8+ and Treg populations were increased in peripheral bloods from animals administered IT NanoDoce. Additional evaluation of the effect of IT NanoDoce on peripheral and local immune cell populations as well as the impact on sites of distant tumor growth are warranted.
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http://dx.doi.org/10.1007/s10637-020-00922-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497695PMC
October 2020
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