Chemically linked phage idiotype vaccination in the murine B cell lymphoma 1 model

Background: B cell malignancies are characterized by clonal
expansion of B cells expressing tumor-specific idiotypes on their
surface. These idiotypes are ideal target antigens for an
individualized immunotherapy. However, previous idiotype vaccines
mostly lacked efficiency due to a low immunogenicity of the
idiotype. The objective of the present study was the determination
of the feasibility, safety and immunogenicity of a novel chemically
linked phage idiotype vaccine. Methods: In the murine B cell
lymphoma 1 model, tumor idiotypes were chemically linked to phage
particles used as immunological carriers. For comparison, the
idiotype was genetically expressed on the major phage coat protein
g8 or linked to keyhole limpet hemocynanin. After intradermal
immunizations with idiotype vaccines, tolerability and humoral
immune responses were assessed. Results: Feasibility and
tolerability of the chemically linked phage idiotype vaccine was
demonstrated. Vaccination with B cell lymphoma 1 idiotype
expressing phage resulted in a significant survival benefit in the
murine B cell lymphoma 1 protection model (60.2 +/- 23.8 days vs.
41.8 +/- 1.6 days and 39.8 +/- 3.8 days after vaccination with wild
type phage or phosphate buffered saline, respectively). Superior
immunogenicity of the chemically linked phage idiotype vaccine
compared to the genetically engineered phage idiotype and keyhole
limpet hemocynanin-coupled idiotype vaccine was demonstrated by
significantly higher B cell lymphoma 1 idiotype-specific IgG levels
after vaccination with chemically linked phage idiotype.
Conclusion: We present a novel, simple, time-and cost-efficient
phage idiotype vaccination strategy, which represents a safe and
feasible therapy and may produce a superior immune response
compared to previously employed idiotype vaccination strategies.