Treatment of squamous carcinoma in mice with a vaccine enriched for cells that induce immunity to squamous carcinoma - A new vaccination strategy

Amla Chopra, Tae Sung Kim, InSug O-Sullivan, Don Martinez, Edward P. Cohen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We report a new vaccination strategy for squamous cell carcinoma (SCC). The vaccine was prepared by transfer of unfractionated DNA-fragments (25 kb) from squamous carcinoma cells (KLN205, DBA/2 origin (H-2d)) into LM mouse fibroblasts (C3H/He origin; H-2k), a highly immunogenic cell line. To enhance their nonspecific immunogenic properties, the fibroblasts were modified before DNA transfer to secrete IL-2 and to express additional allogeneic MHC class I determinants. As the transferred DNA integrates into the genome of the recipient cells, and is replicated as the cells divide, sufficient DNA to prepare the vaccine could be obtained from as few as 107 squamous carcinoma cells (4 mm tumor). Since only a small proportion of the transfected cell-population was expected to have incorporated genes specifying antigens associated with the squamous carcinoma cells (TAA), we devised a novel approach to enrich the vaccine for cells that induce immunity to the SCC.Aliquots of the transfected population were divided into 10 small pools (initial inoculums = 1 × 103). We reasoned that if the starting inoculums were sufficiently small, then the distribution of highly immunogenic and weakly immunogenic cells in each pool would not be the same. Cells from individual pools were allowed to increase in number. A portion of the expanded cell populations were maintained frozen/viable for later recovery. The remaining portions were used to immunize naïve DBA/2 mice. Pools containing greater numbers of immunogenic cells were identified by 2 independent assays. Frozen aliquots of cells from the pool that stimulated immunity to the squamous carcinoma to the greatest extent were recovered and subdivided for additional rounds of immune selection. Enhanced immunity to squamous carcinoma mediated by CD8+ T cells was induced in tumor-bearing mice treated solely by immunization with the enriched cell-population.

Original languageEnglish
Pages (from-to)339-348
Number of pages10
JournalInternational Journal of Cancer
Volume119
Issue number2
DOIs
Publication statusPublished - 2006 Jul 15

Fingerprint

Squamous Cell Carcinoma
Immunity
Vaccination
Vaccines
Therapeutics
DNA
Population
Fibroblasts
Inbred DBA Mouse
Inbred C3H Mouse
Interleukin-2
Immunization
Neoplasms
Cell Count
Genome
T-Lymphocytes
Antigens
Cell Line
Genes

Keywords

  • CTLs
  • DNA-based vaccine
  • Immunotherapy
  • Lung cancer
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Treatment of squamous carcinoma in mice with a vaccine enriched for cells that induce immunity to squamous carcinoma - A new vaccination strategy. / Chopra, Amla; Kim, Tae Sung; O-Sullivan, InSug; Martinez, Don; Cohen, Edward P.

In: International Journal of Cancer, Vol. 119, No. 2, 15.07.2006, p. 339-348.

Research output: Contribution to journalArticle

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