Combined vaccination with idiotype-pulsed allogeneic dendritic cells and soluble protein idiotype for multiple myeloma patients relapsing after reduced-intensity conditioning allogeneic stem cell transplantation.
OBJECTIVE
To combine the use of idiotype-pulsed allogeneic dendritic cells (alloDC) and soluble protein Id conjugated with KLH (Id-KLH) in a vaccine strategy for multiple myeloma (MM).


METHODS
Four MM patients received the combined vaccine after having experienced disease relapse/progression following reduced intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) and failure to rescue therapy with donor lymphocyte infusion or chemotherapy (CHT).


RESULTS
Vaccination was well tolerated and induced an anti-KLH antibody response in all 4 patients as well as substantial cell proliferation. In contrast, no case showed similar effects against either tumor-specific Id or irrelevant isotype control immunoglobulins (Ig). In turn, vaccination was associated with modulation of biological responses linked to both inflammatory and T-cell activation, with secretion of effector Th1 cytokines. In particular, an important increase in the spontaneous ex vivo secretion of TNFalpha, IL-6 and IFNgamma as well as IL-2 and IL-10 was frequently observed prior to the fourth vaccination. Moreover, in vitro stimulation with Id-KLH and Id-KLH plus alloDC, but not with alloDC alone was associated with an enhanced number of TNF-alpha+ T-cells and an increased secretion of IFNgamma and IL-2 before the third and fourth vaccination. From a clinical standpoint, 2 patients had a transient response and 1 has stable disease after stopping vaccination, while 3 of them ultimately progressed.


CONCLUSIONS
The results show for the first time that the use of Id-pulsed alloDC following RIC alloSCT is safe and feasible. However, crucial strategy improvements are warranted to possibly achieve clinical benefit.
Bendandi
Maurizio
M
Laboratory of Immunology, Cell Therapy Area, University Clinic, Center for Applied Medical Research (CIMA), School of Medicine, University of Navarre, Pamplona, Spain. mbendandi@unav.es
Rodríguez-Calvillo
Mercedes
M
Inogés
Susana
S
López-Díaz de Cerio
Ascensión
A
Pérez-Simón
José Antonio
JA
Rodríguez-Caballero
Arancha
A
García-Montero
Andres
A
Almeida
Julia
J
Zabalegui
Natalia
N
Giraldo
Pilar
P
San Miguel
Jesús
J
Orfao
Alberto
A
D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006433:Hemocyanins / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology* / Q000302:isolation & purification; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D010865:Pilot Projects; D012008:Recurrence; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
D019496:Cancer Vaccines; D016207:Cytokines; D007130:Immunoglobulin Idiotypes; D018074:Vaccines, Conjugate; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin