Contribution of dead cells to the immunogenicity of an autologous, hapten-modified melanoma vaccine.
We have reported that treatment of melanoma patients with a vaccine consisting of autologous tumor cells modified with the hapten, dinitrophenyl (DNP), induced delayed-type hypersensitivity (DTH) to autologous, unmodified tumor cells. Moreover, this response was a significant and independent predictor of survival. We analyzed the vaccines prepared for 284 patients who were treated following resection of regional or distant metastases to determine whether the dose and composition correlated with immunological response. Regression analysis showed no significant association between the magnitude of this DTH response and the number of live (trypan blue-excluding) melanoma cells per dose. In fact, vaccines containing higher numbers or higher proportions of dead, but intact, tumor cells induced larger DTH responses to autologous unmodified tumor. The observation that dead tumor cells are immunogenic may be applicable to other cellular human cancer vaccines and underscores the need for applying pharmacological principles to cancer immunotherapy.
Berd
David
D
Department of Medicine, Division of Medical Oncology of Thomas Jefferson University, 1015 Walnut Street, Suite 1024, Philadelphia, PA 19107, USA. d_berd@mail.jci.tju.edu
D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002452:Cell Count; D002469:Cell Separation; D002470:Cell Survival; D004136:Dinitrobenzenes / Q000276:immunology; D006241:Haptens; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007271:Injections, Intradermal; D008545:Melanoma / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D009362:Neoplasm Metastasis; D015996:Survival Rate
D019496:Cancer Vaccines; D004136:Dinitrobenzenes; D006241:Haptens