Anti-tumor Immunomodulation

Concentrated, sustained local delivery of large surface area microparticles (LSAMs) results in immunogenic tumor cell death with preclinical and clinical evidence of local/peripheral anti-tumor immunomodulation.

Clinical Examples of Increased Anti-tumor Immunomodulation in Pancreatic Cancer

Immune characterization: Increased tumor infiltration of CD4+ Helper T and CD8+ Cytotoxic T cells into the tumor following NanoPac® injections

Pre-Injection Biopsy

10858930-02, R000

Pre-Injection Biopsy

10858934-03, R007

CD3+ CD4+ CD8+ PanCK: T helper cells are in yellow and T cytotoxic cells are in magenta

ROI selected based on maximum density of CD8+ T Cells

Immune characterization in a subject with no evidence of primary tumor resection

Tumor Microenvironment

 

Favorable changes in innate and adaptive immunity following IT NanoPac® treatment

  • Increase in CD4+ Helper T, CD8+ Cytotoxic T cells (including PD-1+), Memory Tregs in TME

  • Decrease in PD-L1+ Tumor Cells

  • Decrease in Myeloid, MDSC

  • Increase in tumor-associated NK Cells

Preclinical Example of IT NanoDoce® ± IO Combination Treatment

Metastatic Breast Cancer (4T1-Luc) treated with IT NanoDoce systemic anti-mPD-L1 combo or IT NanoDoce & systemic anti‑mCTLA‑4

API Crystals

IT NanoDoce: 50 mg/kg; Q4D x 4
IP anti-mPD-L1: 10 mg/kg Q3Dx2; 3, QDx1
IP anti-mCTLA-4: 10 mg/kg (Q3Dx2; 3) x2

Preclinical Examples of Increased Immune Response

Bladder Cancer (UMUC-3/Mice) Treated with Intratumoral NanoDoce
F4-80 brown stain shows macrophages in and around dead and dying tumor. Negative control shows viable tumor cells.

NANO_IT-NanoDoce-UMUC-3-cell-line-F4-80-stainNOARROWS

Negative Control

Bladder Cancer (UMUC-3/Mice)
Treated with Intratumoral NanoDoce
CD16 brown stain shows admixture of natural killers, macrophages, monocytes in and around dead and dying tumor. Negative control shows viable tumor cells.

NANO_IT-NanoDoce-UMUC-3-cell-line-CD16-stain5_29

Negative Control

Non-Small Cell Lung Cancer (Calu-3/Rat) Treated with Inhaled NanoPac
CD11b brown stain shows admixture of natural killers, macrophages, dendritic cells in and around dead and dying tumor. Negative control shows viable tumor cells.

NANO_IH-NanoPac-Calu-3-cell-line-CDllb-stain5_29

Negative Control

Publications Demonstrating Immunogenic Effects of NanoPac and NanoDoce

NanoPac Review Paper: Preclinical and Clinical Evidence

Intratumoral NanoDoce Preclinical Immunogenic Response in Syngeneic Renal Tumors

NanoDoce + anti-mCTLA-4 Preclinical Combination Study in Metastatic Breast Tumors

 

References:  Maulhardt et al, Cancers, 2019.  Verco et al, JAMPDD, 2019. NanOlogy internal data, 2015-2022.