Effect of linkage of transduction domain sequences to a lymphoma idiotype DNA vaccine on vaccine effectiveness.
Patient idiotype-specific vaccines for treatment of non-Hodgkin's lymphoma have shown promise in clinical trials, encouraging efforts to enhance the effectiveness of idiotype vaccines further. It has previously been found that for some other types of experimental vaccines, the addition of transduction domains has improved vaccine immunogenicity. Transduction domains are short amino acid sequences that are capable of increasing transport through cellular membranes. In this study, we tested murine B cell 38C13 lymphoma idiotype DNA vaccines with human immunodeficiency virus (HIV) Tat-derived transduction sequences for efficacy against 38C13 challenge. The rate of tumor onset was similar for the idiotype and transduction domain-conjugated idiotype vaccine groups. At days 22-23 postchallenge, the number of surviving mice was significantly higher in the group that had received a DNA vaccine consisting of the 38C13 idiotype sequence plus modified Tat transduction sequence, in comparison with the group that received idiotype-only vaccines. Although the overall survival difference was not statistically significant following day 24, a trend toward an increased survival rate for mice receiving idiotype plus Tat-derived transduction domains was maintained through day 106 postchallenge. Thus, the addition to idiotype vaccines of specific sequences that facilitate intracellular transport may have potential to improve the effectiveness of such vaccines.
Ashour
Abdel-Kader
AK
Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Petersen
Jason L
JL
McIlhaney
Mary M
MM
Vose
Julie M
JM
Solheim
Joyce C
JC
D000818:Animals; D018033:Antibodies, Bispecific; D000912:Antibodies, Neoplasm / Q000096:biosynthesis*; D019496:Cancer Vaccines / Q000627:therapeutic use; D006678:HIV / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000627:therapeutic use*; D016233:Immunotherapy, Active; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D051379:Mice; D017434:Protein Structure, Tertiary; D016019:Survival Analysis; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000627:therapeutic use
D018033:Antibodies, Bispecific; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D019444:Vaccines, DNA