Person:
Pfirschke, Christina

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Pfirschke

First Name

Christina

Name

Pfirschke, Christina

Filters

2015 - 20172

Settings

Author's Publications: search.filters.isAuthorOfPublication.650a26f0-3ab3-4f9f-aae1-a844ad26b9f1

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging
    (Nature Publishing Group, 2017) Cuccarese, Michael F.; Dubach, J. Matthew; Pfirschke, Christina; Engblom, Camilla; Garris, Christopher; Miller, Miles; Pittet, Mikael; Weissleder, Ralph
    Involvement of the immune system in tumour progression is at the forefront of cancer research. Analysis of the tumour immune microenvironment has yielded a wealth of information on tumour biology, and alterations in some immune subtypes, such as tumour-associated macrophages (TAM), can be strong prognostic indicators. Here, we use optical tissue clearing and a TAM-targeting injectable fluorescent nanoparticle (NP) to examine three-dimensional TAM composition, tumour-to-tumour heterogeneity, response to colony-stimulating factor 1 receptor (CSF-1R) blockade and nanoparticle-based drug delivery in murine pulmonary carcinoma. The method allows for rapid tumour volume assessment and spatial information on TAM infiltration at the cellular level in entire lungs. This method reveals that TAM density was heterogeneous across tumours in the same animal, overall TAM density is different among separate pulmonary tumour models, nanotherapeutic drug delivery correlated with TAM heterogeneity, and successful response to CSF-1R blockade is characterized by enhanced TAM penetration throughout and within tumours.
  • Thumbnail Image
    Publication
    Tumor associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug
    (2015) Miller, Miles; Zheng, Yao-Rong; Gadde, Suresh; Pfirschke, Christina; Zope, Harshal; Engblom, Camilla; Kohler, Rainer; Iwamoto, Yoshiko; Yang, Katherine; Askevold, Bjorn; Kolishetti, Nagesh; Pittet, Mikael; Lippard, Stephen J.; Farokhzad, Omid; Weissleder, Ralph
    Therapeutic nanoparticles (TNPs) aim to deliver drugs more safely and effectively to cancers, yet clinical results have been unpredictable owing to limited in vivo understanding. Here we use single-cell imaging of intratumoral TNP pharmacokinetics and pharmacodynamics to better comprehend their heterogeneous behavior. Model TNPs comprised of a fluorescent platinum(IV) pro-drug and a clinically-tested polymer platform (PLGA-b-PEG) promote long drug circulation and alter accumulation by directing cellular uptake toward tumor associated macrophages (TAMs). Simultaneous imaging of TNP vehicle, its drug payload, and single-cell DNA damage response reveals that TAMs serve as a local drug depot that accumulates significant vehicle from which DNA damaging Pt payload gradually releases to neighboring tumor cells. Correspondingly, TAM depletion reduces intratumoral TNP accumulation and efficacy. Thus, nanotherapeutics co-opt TAMs for drug delivery, which has implications for TNP design and for selecting patients into trials.