Affiliations: [a] Department of Surgery, University of Calgary, Calgary, AB, Canada | [b] Department of Neurosurgery, University of Utah, Salt Lake City, UT, USA | [c] Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA | [d] BioSante Pharmaceuticals, Inc., Doylestown, PA, USA
Correspondence:
[*]
Corresponding author: Arpad Z. Barabas, Department of Surgery, University of Calgary, B702 Health Sciences Centre, 3330 Hospital Dr. NW, Calgary, AB, T2N 4N1 Canada. Tel.: +1 403 220 8901; Fax: +1 403 270 8795; E-mail:barabas@ucalgary.ca
Abstract: Objectives were to: 1) induce a lytic IgG antibody (ab) response (via the so
called `third vaccination method') against CD38 antigen (ag) residing on the
extra-cellular domain of multiple myeloma (MM) cells in recipient rabbits,
by combining the CD38 ag with donor-derived anti-CD38 ag lytic IgG ab into
an immune complex (IC); and 2) determine whether abs produced would cause
complement-mediated lysis (in vitro) of human MM cells containing CD38 ag. The
vaccine was created in a two-step process. First, ab (rabbit anti-CD38 ag
IgG ab) was raised in donor rabbits by injections of low molecular weight
soluble CD38 ag in Freund's complete adjuvant (FCA) and aqueous solution.
Second, transfer of pathogenic lytic IgG ab response into recipient rabbits
was achieved by injections of ICs composed of CD38 ag and homologous
anti-CD38 ag IgG ab. Consequently, recipient rabbits produced the same ab
with the same specificity against the target ag as was present in the
inoculum, namely agglutinating, precipitating and lytic (as demonstrated in vitro).
In an in vitro study, in the presence of complement, donor and recipient rabbits'
immune sera caused lysis of CD38 ag associated human MM cells. The most
effective lytic ab response causing sera were those from donor rabbits
injected with CD38 ag in FCA and those from rabbits injected with ICs,
especially when they were administered in adjuvants. These results provided
proof of concept that the third vaccination method has good potential as a
stand-alone and efficacious method of controlling cancer.
