Intratumoral Injection of Large Surface Area Microparticle Taxanes in Carcinomas Increases Immune Effector Cell Concentrations, Checkpoint Expression, and Synergy with Checkpoint Inhibitors: A Review of Preclinical and Clinical Studies.

This review summarizes development of large surface area microparticle paclitaxel (LSAM-PTX) and docetaxel (LSAM-DTX) for local treatment of primary carcinomas with emphasis on immunomodulation. Intratumoral (IT) delivery of LSAM-PTX and LSAM-DTX provides continuous, therapeutic drug levels for several weeks. Preclinical studies and clinical trials reported a reduction in tumor volume (TV) and immunomodulation in primary tumor and peripheral blood with increases in innate and adaptive immune cells and decreases in suppressor cells.

Intratumoral Treatment of Melanoma Tumors with Large Surface Area Microparticle Paclitaxel and Synergy with Immune Checkpoint Inhibition.

The effects of intratumoral (IT) large surface area microparticle paclitaxel (LSAM-PTX) alone and in combination with systemic administration of the programmed cell death protein antibody (anti-mPD-1) were evaluated in a syngeneic murine model of melanoma. Groups of mice with subcutaneously implanted Clone M3 (Cloudman S91) tumors were treated with single and combination therapies. Tumor volume (TV) measurements, body weights, and clinical observations were followed in-life.

Response of Locally Advanced Pancreatic Cancer to Intratumoral Injection of Large Surface Area Microparticle Paclitaxel: Initial Report of Safety and Clinical Outcome.

Objectives: Large surface area microparticle paclitaxel (LSAM-PTX) provides an intratumoral (IT) chemotherapeutic depot. Safety, tolerability, and tumor response to IT LSAM-PTX delivered by endoscopic ultrasound-fine needle injection were evaluated in subjects with unresectable locally advanced pancreatic cancer (LAPC).

Methods: Ten subjects treated in a dose escalation phase and 22 additional subjects receiving 2 injections, 4 weeks apart, of 15 mg/mL LSAM-PTX were followed for 12 months.

Early phase trial of intracystic injection of large surface area microparticle paclitaxel for treatment of mucinous pancreatic cysts.

Mucinous pancreatic cystic lesions (PCLs) have the potential for malignant transformation, for which the only accepted curative modality is surgery. A novel intracystic therapy with large surface area microparticle paclitaxel (LSAM-PTX) may treat PCLs without local or systemic toxicities. Safety and preliminary efficacy of LSAM-PTX for the treatment of PCLs administered by endoscopic ultrasound-guided fine-needle injection (EUS-FNI) was evaluated.

Local administration of large surface area microparticle docetaxel to solid carcinomas induces direct cytotoxicity and immune-mediated tumoricidal effects: preclinical and clinical studies.

This report describes local administration of large surface area microparticle docetaxel (LSAM-DTX: ~ 3.5- to 7.5-µm-sized particles with high relative surface area) in preclinical oncology models and in a clinical trial in urothelial carcinoma.