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.
BarabasA.Z., WeirD.M., ColeC.D., BarabasA.D., BahlisN.J., GraeffR.M. et al., Preventing and treating chronic disorders using the modified vaccination technique, Front Biosci (2009), 143892-143898.
2.
BarabasA.Z., ColeC.D., BarabasA.D., GraeffR.M., LafreniereR. and WeirD.M., Correcting autoimmune anomalies in autoimmune disorders by immunological means, employing the modified vaccination technique, Autoimmun Rev8(7) (2009), 552-557.
3.
BerinsteinN.L., Enhancing cancer vaccines with immunomodulators, Vaccine25(Suppl 2) (2007), 2B72-2B88.
4.
FeldmannM. and SteinmanL., Design of effective immunotherapy for human autoimmunity, Nature435(7042) (2005), 612-619.
5.
LolliniP.L. and ForniG., Antitumor vaccines: is it possible to prevent a tumor?Cancer Immunol Immunother51(8) (2002), 409-416.
6.
MilsteinC. and WaldmannH., Optimism after much pessimism: what next?Curr Opin Immunol11(5) (1999), 589-591.
7.
PetrovskyN. and AguilarJ.C., Vaccine adjuvants: current state and future trends, Immunol Cell Biol82(5) (2004), 488-496.
8.
RosenbergS.A., YangJ.C. and RestifoN.P., Cancer immunotherapy: moving beyond current vaccines, Nat Med10(9) (2004), 909-9915.
9.
SioudM., Does our current understanding of immune tolerance, autoimmunity, and immunosuppressive mechanisms facilitate the design of efficient cancer vaccines?Scand J Immunol70(6) (2009), 516-525.
10.
BarabasA.Z., ColeC.D., BarabasA.D., BahlisN.J. and LafreniereR., New vaccination technology for endogenous antigen-derived ailments, IDrugs11(2) (2008), 111-115.
11.
CopeA.P. and FeldmannM., Emerging approaches for the therapy of autoimmune and chronic inflammatory disease, Curr Opin Immunol16(6) (2004), 780-786.
12.
ReffM.E., CarnerK., ChambersK.S., ChinnP.C., LeonardJ.E., RaabR. et al., Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20, Blood83(2) (1994), 435-445.
13.
RomondE.H., PerezE.A., BryantJ., SumanV.J., Geyer Jr.C.E., DavidsonN.E. et al., Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer, N Engl J Med353(16) (2005), 1673-1684.
14.
SlamonD.J., Leyland-JonesB., ShakS., FuchsH., PatonV., BajamondeA. et al., Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2, N Engl J Med344(11) (2001), 783-792.
15.
BarabasA.Z. and LafreniereR., Antigen-specific down-regulation of immunopathological events in an experimental autoimmune kidney disease, Autoimmun Rev4(8) (2005), 565-570.
16.
BarabasA.Z., ColeC.D., BarabasA.D. and LafreniereR., Down-regulation of pathogenic autoantibody response in a slowly progressive Heymann nephritis kidney disease model, Int J Exp Pathol85(6) (2004), 321-334.
17.
BarabasA.Z., ColeC.D., BarabasA.D. and LafreniereR., Downregulation of a pathogenic autoantibody response by IgM autoantibodies directed against the nephritogenic antigen in slowly progressive Heymann nephritis, Pathol Int56(4) (2006), 181-190.
18.
BarabasA.Z., ColeC.D., BarabasA.D. and LafreniereR., A modified vaccination technique for the prevention and treatment of an experimental autoimmune kidney disease, Ann NY Acad Sci (2007), 1110619-1110629.
19.
LiuQ., KriksunovI.A., GraeffR., MunshiC., LeeH.C. and HaoQ., Crystal structure of human CD38 extracellular domain, Structure13(9) (2005), 1331-1339.
20.
MunshiC.B., FryxellK.B., LeeH.C. and BrantonW.D., Large-scale production of human CD38 in yeast by fermentation, Methods Enzymol (1997), 280318-280330.
21.
MunshiC., AarhusR., GraeffR., WalsethT.F., LevittD. and LeeH.C., Identification of the enzymatic active site of CD38 by site-directed mutagenesis, J Biol Chem275(28) (2000), 21566-21571.
22.
BlattmanJ.N. and GreenbergP.D., Cancer immunotherapy: A treatment for the masses, Science305(5681) (2004), 200-205.
23.
RoyR., New trends in carbohydrate-based vaccines, Drug Discovery Today: Technologies1(3) (2004), 327-336.
24.
EngelhardV.H., BullockT.N., ColellaT.A., SheasleyS.L. and MullinsD.W., Antigens derived from melanocyte differentiation proteins: Self-tolerance, autoimmunity, and use for cancer immunotherapy, Immunol Rev (2002), 188136-188146.
25.
GirolomoniG. and Ricciardi-CastagnoliP., Dendritic cells hold promise for immunotherapy, Immunol Today18(3) (1997), 102-104.
26.
GoforthR., SalemA.K., ZhuX., MilesS., ZhangX.Q., LeeJ.H. et al., Immune stimulatory antigen loaded particles combined with depletion of regulatory T-cells induce potent tumor specific immunity in a mouse model of melanoma, Cancer Immunol Immunother58(4) (2009), 517-530.
27.
GunzerM. and GrabbeS., Dendritic cells in cancer immunotherapy, Crit Rev Immunol21(1-3) (2001), 133-145.
28.
SatoT., Active specific immunotherapy with hapten-modified autologous melanoma cell vaccine, Cancer Immunol Immunother43(3) (1996), 174-179.
29.
SerreK., MachyP., GrivelJ.C., JollyG., BrunN., BarbetJ. et al., Efficient presentation of multivalent antigens targeted to various cell surface molecules of dendritic cells and surface Ig of antigen-specific B cells, J Immunol161(11) (1998), 6059-6067.
30.
CzuraA.W. and CzuraC.J., CD38 and CD157: biological observations to clinical therapeutic targets, Mol Med12(11-12) (2006), 309-311.
31.
EllisJ.H., BarberK.A., TuttA., HaleC., LewisA.P., GlennieM.J. et al., Engineered anti-CD38 monoclonal antibodies for immunotherapy of multiple myeloma, J Immunol155(2) (1995), 925-937.
32.
StevensonF.K., BellA.J., CusackR., HamblinT.J., SladeC.J., SpellerbergM.B. et al., Preliminary studies for an immunotherapeutic approach to the treatment of human myeloma using chimeric anti-CD38 antibody, Blood77(5) (1991), 1071-1079.
33.
McLaughlinP., Grillo-LopezA.J., LinkB.K., LevyR., CzuczmanM.S., WilliamsM.E. et al., Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program, J Clin Oncol16(8) (1998), 2825-2833.
34.
HainsworthJ.D., Rituximab as first-line and maintenance therapy for patients with indolent non-Hodgkin's lymphoma: Interim follow-up of a multicenter phase II trial, Semin Oncol29(1 Suppl 2) (2002), 25-29.
35.
DornerT., RadbruchA. and BurmesterG.R., B-cell-directed therapies for autoimmune disease, Nat Rev Rheumatol5(8) (2009), 433-441.
36.
LevesqueM.C., Translational Mini-Review Series on B Cell-Directed Therapies: Recent advances in B cell-directed biological therapies for autoimmune disorders, Clin Exp Immunol157(2) (2009), 198-208.
37.
ByrdJ.C., WaselenkoJ.K., ManeatisT.J., MurphyT., WardF.T., MonahanB.P. et al., Rituximab therapy in hematologic malignancy patients with circulating blood tumor cells: association with increased infusion-related side effects and rapid blood tumor clearance, J Clin Oncol17(3) (1999), 791-795.
38.
BarabasA.Z., ColeC.D., BarabasA.D. and LafreniereR., Production of a new model of slowly progressive Heymann nephritis, Int J Exp Pathol84(6) (2003), 245-258.
39.
BarabasA.Z., ColeC.D., LafreniereR. and WeirD.M., Regaining tolerance to a self-antigen by the modified vaccination technique, Clin Rev Allergy Immunol45(2) (2013), 193-201.
