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Full Remission of CAR-Deficient Tumors by DOTAP-Folate Liposome Encapsulation of Adenovirus

Ching-Hsin Huang1, Tao Dong1, Abraham T Phung1

  • 1Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, California 92037, United States.

ACS Biomaterials Science & Engineering
|November 17, 2022
PubMed

Insights

DOTAP-folate liposomes enhance adenovirus gene therapy in CAR-deficient cancers. This novel delivery system improved cancer cell killing and achieved significant tumor remission in preclinical models, offering a promising cancer treatment strategy.

Area of Science:

  • Biotechnology
  • Gene Therapy
  • Oncolytic Viruses

Background:

  • Adenovirus (Ad) vectors are promising for gene therapy but require the coxsackievirus and adenovirus receptor (CAR) for efficient cell entry.
  • Low CAR expression in many human cancers limits the efficacy of adenoviral gene therapies.

Purpose of the Study:

  • To develop and evaluate DOTAP-folate liposomes as a delivery system to enhance Ad transfection efficiency in CAR-deficient cells.
  • To assess the therapeutic potential of oncolytic Ad encapsulated in DOTAP-folate liposomes for cancer treatment.

Main Methods:

  • Synthesis of cationic 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-folate liposomes encapsulating replication-deficient and replication-competent Ad.
  • Evaluation of transfection efficiency in CAR-deficient cell lines.
  • Assessment of tumor cell killing ability and in vivo efficacy in a CT26 colon carcinoma murine model.

Main Results:

  • DOTAP-folate liposomes significantly improved Ad transfection efficiency in various CAR-deficient cell lines.
  • Encapsulation of oncolytic Ad (TAV255) in DOTAP-folate liposomes (TAV255-Df) resulted in a 5-fold increase in tumor cell killing ability.
  • Intratumoral injection of TAV255-Df led to 67% tumor remission, prolonged survival, and induced anti-cancer immunity in mice.

Conclusions:

  • DOTAP-folate liposomes represent a feasible strategy to overcome CAR-deficiency limitations for Ad-based gene therapy.
  • This liposomal delivery system holds significant potential for enhancing the efficacy of oncolytic adenoviruses in cancer treatment.
Keywords:
DOTAPcoxsackievirus and adenovirus receptorfolate targetingliposomeoncolytic virus

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