Adenoviral vectors expressing lymphotactin and interleukin 2 or lymphotactin and interleukin 12 synergize to facilitate tumor regression in murine breast cancer models

Hum Gene Ther. 1999 Mar 20;10(5):697-709. doi: 10.1089/10430349950018463.


We have previously demonstrated that intratumoral injection with Ad vectors expressing IL-2 or IL-12 can induce regression in a murine breast cancer model. These IL-2- or IL-12-induced antitumor responses were mainly mediated by Ag-specific T cells. Lymphotactin is a novel lymphocyte chemokine that can cause local accumulation of CD4+, CD8+, and NK cells. We hypothesized that addition of lymphotactin may enhance the antitumor immune responses induced by locally produced IL-2 and IL-12 as we have previously shown. To this end we constructed two double-recombinant adenoviral vectors expressing lymphotactin along with either IL-2 (Ad5 Lym/IL-2) or IL-12 (Ad5 Lym/IL-12). Subcutaneous injection of polyoma middle T (PyMT) or Neu (8142) transgenically derived breast adenocarcinoma cells, in the hind flank of FVB/n mice, results in the formation of tumor nodules in 14-21 days. We show that these constructs elicit potent antitumor responses when administered intratumorally. The antitumor responses are long lasting as determined by rechallenge experiments and hence demonstrate a protective immunity. These observations indicate that by augmenting the antitumor response with adenoviral vectors expressing lymphotactin in combination with IL-2 or IL-12 is a novel way to enhance immunotherapeutic approaches.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / metabolism
  • Animals
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line
  • Chemokines, C*
  • Cytotoxicity Tests, Immunologic
  • Drug Therapy, Combination
  • Genetic Therapy*
  • Genetic Vectors
  • Immunohistochemistry
  • Interferon-gamma / metabolism
  • Interleukin-12 / genetics*
  • Interleukin-12 / therapeutic use
  • Interleukin-2 / genetics*
  • Interleukin-2 / therapeutic use
  • Interleukin-4 / metabolism
  • Lymphokines / genetics*
  • Lymphokines / therapeutic use
  • Mammary Neoplasms, Experimental / therapy*
  • Mice
  • Mice, Transgenic
  • Models, Genetic
  • Sialoglycoproteins / genetics*
  • Sialoglycoproteins / therapeutic use
  • Time Factors


  • CD3 Complex
  • Chemokines, C
  • Interleukin-2
  • Lymphokines
  • Sialoglycoproteins
  • Xcl1 protein, mouse
  • lymphotactin
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma