INGN-225: A Dendritic Cell-Based p53 Vaccine (Ad.p53-DC) in Small Cell Lung Cancer: Observed Association Between Immune Response and Enhanced Chemotherapy Effect

Expert Opin Biol Ther. 2010 Jun;10(6):983-91. doi: 10.1517/14712598.2010.484801.

Abstract

Importance of the field: Novel approaches are needed for patients with small cell lung cancer (SCLC), as response after relapse is poor with standard therapies. p53 gene mutations often occur, resulting in tumoral protein overexpression and allowing for their recognition by p53-specific cytotoxic T cells.

Areas covered in this review: We describe the characteristics and manufacturing of INGN-225, a p53-modified adenovirus-tranduced dendritic cell vaccine, and review available data, to understand INGN-225's role in SCLC treatment. We discuss our pre-clinical, early Phase I/II, and ongoing randomized Phase II studies.

What the reader will gain: INGN-225 was well tolerated (all toxicities <or=grade 2) in the Phase I/II trial (54 patients receiving at least 1 dose). Specific anti-p53 immune response was positive in 18/43 (41.8%) patients, with overall post-INGN-225 response observed in 17/33 (51.5%) and immune response data available in 29 (14 positive, 15 negative). Post-INGN-225 response was observed in 11/14 (78.6%) and 5/15 (33%) patients with positive and negative immune responses, respectively.

Take home message: INGN-225 is safe, induces a significant immune response, and appears to sensitize SCLC to subsequent chemotherapy. Improvements in immune response induction and understanding the chemotherapy-immunotherapy synergism will determine INGN-225's future role as an anticancer therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use*
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Dendritic Cells / immunology*
  • Humans
  • Immunotherapy*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / therapy*
  • Randomized Controlled Trials as Topic
  • Small Cell Lung Carcinoma / immunology*
  • Small Cell Lung Carcinoma / therapy*
  • Tumor Suppressor Protein p53 / immunology*

Substances

  • Cancer Vaccines
  • INGN 225
  • Tumor Suppressor Protein p53