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Updated: Aug 7, 2026
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase
Dmitri B Kirpotin1, Daryl C Drummond, Yi Shao
1Hermes Biosciences Inc., South San Francisco, CA, USA.
Abstract:
We describe evidence for a novel mechanism of monoclonal antibody (MAb)-directed nanoparticle (immunoliposome) targeting to solid tumors in vivo. Long-circulating immunoliposomes targeted to HER2 (ErbB2, Neu) were prepared by the conjugation of anti-HER2 MAb fragments (Fab' or single chain Fv) to liposome-grafted polyethylene glycol chains. MAb fragment conjugation did not affect the biodistribution or long-circulating properties of i.v.-administered liposomes. However, antibody-directed targeting also did not increase the tumor localization of immunoliposomes, as both targeted and nontargeted liposomes achieved similarly high levels (7-8% injected dose/g tumor tissue) of tumor tissue accumulation in HER2-overexpressing breast cancer xenografts (BT-474). Studies using colloidal gold-labeled liposomes showed the accumulation of anti-HER2 immunoliposomes within cancer cells, whereas matched nontargeted liposomes were located predominantly in extracellular stroma or within macrophages. A similar pattern of stromal accumulation without cancer cell internalization was observed for anti-HER2 immunoliposomes in non-HER2-overexpressing breast cancer xenografts (MCF-7). Flow cytometry of disaggregated tumors posttreatment with either liposomes or immunoliposomes showed up to 6-fold greater intracellular uptake in cancer cells due to targeting. Thus, in contrast to nontargeted liposomes, anti-HER2 immunoliposomes achieved intracellular drug delivery via MAb-mediated endocytosis, and this, rather than increased uptake in tumor tissue, was correlated with superior antitumor activity. Immunoliposomes capable of selective internalization in cancer cells in vivo may provide new opportunities for drug delivery.
Insights
Monoclonal antibody-directed immunoliposomes achieve superior antitumor activity by enabling intracellular drug delivery into cancer cells, not by increasing overall tumor accumulation. This novel targeting mechanism enhances therapeutic potential for solid tumors.
Area of Science:
- Nanomedicine
- Oncology
- Immunology
Background:
- Monoclonal antibodies (MAbs) are utilized for targeted drug delivery.
- Immunoliposomes are nanoparticles engineered for targeted delivery.
- HER2 (ErbB2, Neu) is a target in some breast cancers.
Purpose of the Study:
- To investigate a novel mechanism of MAb-directed nanoparticle targeting to solid tumors.
- To evaluate the in vivo tumor targeting and intracellular delivery of HER2-targeted immunoliposomes.
- To correlate targeting mechanisms with antitumor activity.
Main Methods:
- Preparation of long-circulating immunoliposomes by conjugating anti-HER2 MAb fragments to liposome-grafted polyethylene glycol chains.
- Assessment of liposome biodistribution, tumor localization, and cellular uptake in HER2-overexpressing and non-overexpressing breast cancer xenografts using colloidal gold labeling and flow cytometry.
- Evaluation of antitumor activity in vivo.
Main Results:
- MAb fragment conjugation did not alter liposome biodistribution or circulation time.
- Both targeted and nontargeted liposomes showed similar high tumor tissue accumulation.
- Anti-HER2 immunoliposomes demonstrated MAb-mediated endocytosis and intracellular accumulation within cancer cells, unlike nontargeted liposomes.
- Targeting resulted in up to 6-fold greater intracellular uptake in cancer cells.
- Superior antitumor activity was correlated with intracellular drug delivery, not increased tumor uptake.
Conclusions:
- Anti-HER2 immunoliposomes achieve selective intracellular drug delivery via MAb-mediated endocytosis.
- This intracellular delivery mechanism, rather than enhanced tumor accumulation, drives superior antitumor efficacy.
- Immunoliposomes capable of selective cancer cell internalization offer promising new avenues for cancer drug delivery.
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