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Development and Evaluation of Tri-Functional Immunoliposomes for the Treatment of HER2 Positive Breast Cancer

  • Tanaya Vaidya
  • Robert M. Straubinger
  • Sihem Ait-Oudhia
Research Paper
  • 236 Downloads

Abstract

Purpose

Trastuzumab combined with Doxorubicin (DOX) demonstrates significant clinical activity in human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC). However, emergence of treatment resistance and trastuzumab associated cardiotoxicity remain clinical challenges. In an effort to improve patient outcome, we have developed and evaluated novel tri-functional immunoliposomes (TFIL) that target HER2-receptors on BC cells and CD3-receptors on T-lymphocytes, and deliver DOX.

Methods

Trastuzumab (anti-HER2) and OKT-3 (anti-CD3) antibodies were conjugated to liposomes using a micelle-transfer method. Cytotoxicity of targeted immunoliposomes loaded with DOX was examined in vitro on HER2-positive BC cells (BT474), with peripheral blood monocytic cells (PBMC) as immune effector cells.

Results

TFIL demonstrated high antibody-liposome conjugation ratios (100–130 μg protein/μmol phospholipid) and cargo capacity (0.21 mol:mol drug:lipid), highly efficient DOX loading (>90%), a particle size favorable for extended circulation (~150 nm), and good stability (up to 3 months at 4°C). In the presence of PBMCs, TFIL showed complete killing of BT474 cells, and were superior to mono-targeted trastuzumab-bearing liposomes, non-targeted liposomes, and free Trastuzumab and DOX.

Conclusions

Novel anti-HER2xCD3 + DOX TFIL show promise as a means to both engage immune cells against HER2 positive breast cancer cells and deliver chemotherapy, and have the potential to improve clinical outcomes.

KEY WORDS

anti-CD3 HER2-positive breast cancer immunoliposomes trastuzumab doxorubicin 

Abbreviations

BC

Breast Cancer

CD3

Cluster of Differentiation Receptor Type 3

CTLs

Cytotoxic T Lymphocytes

DOX

Doxorubicin

HER2

Human Epidermal Growth Factor Receptor Type 2

PBMCs

Peripheral Blood Mononuclear Cells

TFIL

Tri-Functional Immunoliposomes

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tanaya Vaidya
    • 1
  • Robert M. Straubinger
    • 2
  • Sihem Ait-Oudhia
    • 1
  1. 1.Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of PharmacyUniversity of FloridaOrlandoUSA
  2. 2.Department of Pharmaceutical SciencesUniversity at Buffalo, State University of New YorkBuffaloUSA

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