Enrichment of a squamous carcinoma vaccine.
We describe a new vaccination strategy for squamous cell carcinoma. In a mouse model, the vaccine is prepared by transfer of unfractionated DNA-fragments (25 kb) from KLN205 cells, a squamous carcinoma cell line (DBA/2 mouse origin [H-2(d)]) into LM cells, a highly immunogenic mouse fibroblast cell line that expresses allogeneic major histocompatibility complex (MHC) class I-determinants (H-2(k)). The number of vaccine cells can then be expanded for multiple immunizations, as desired. As only a small proportion of the transfected cell population was expected to have incorporated DNA segments that included genes specifying antigens associated with the squamous carcinoma cells, we devised a novel strategy to enrich the vaccine for cells that induced immunity to the squamous carcinoma cells. Twenty-five percent of tumor-bearing mice treated by immunization with the vaccine appeared to have rejected the squamous carcinoma cells; they survived indefinitely (more than 70 days). The therapeutic benefits of the enriched vaccine could be further enhanced by treating the tumor-bearing mice with paclitaxel, a chemotherapeutic agent, followed by immunization with the enriched vaccine. Under these circumstances, 75% of mice with squamous carcinoma appeared to have rejected the squamous carcinoma cells. Toxic effects including the development of autoimmune disease were not detected in tumor-bearing mice receiving the combined therapy.
O-Sullivan
InSug
I
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.
Chopra
Amla
A
Cohen
Edward P
EP
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019496:Cancer Vaccines / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D017024:Chemotherapy, Adjuvant; D005347:Fibroblasts / Q000276:immunology / Q000637:transplantation*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D017239:Paclitaxel / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D019444:Vaccines, DNA; D017239:Paclitaxel