Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen.
OBJECTIVE
The idiotype (Id) of the immunoglobulin on a given B-cell malignancy is a clonal marker that can serve as a tumor-specific antigen. We developed a novel vaccine formulation by incorporating Id protein with liposomal lymphokine that was more potent than a prototype, carrier-conjugated Id protein vaccine in preclinical studies. In the present study, we evaluated the safety and immunogenicity of this vaccine in follicular lymphoma patients.


METHODS
Ten patients with advanced-stage follicular lymphoma were treated with five doses of this second generation vaccine after chemotherapy-induced clinical remission. All patients were evaluated for cellular and humoral immune responses.


RESULTS
Autologous tumor and Id-specific type I cytokine responses were induced by vaccination in 10 and 9 patients, respectively. Antitumor immune responses were mediated by both CD4+ and CD8+ T cells, were human lymphocyte antigen class I and II associated, and persisted 18 months beyond the completion of vaccination. Specific anti-Id antibody responses were detected in four patients. After a median follow-up of 50 months, 6 of the 10 patients remain in continuous first complete remission.


CONCLUSIONS
This first clinical report of a liposomal cancer vaccine demonstrates that liposomal delivery is safe, induces sustained tumor-specific CD4+ and CD8+ T-cell responses in lymphoma patients, and may serve as a model for vaccine development against other human cancers and infectious pathogens.
Neelapu
Sattva S
SS
Experimental and Transplantation Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. sneelapu@mdanderson.org
Baskar
Sivasubramanian
S
Gause
Barry L
BL
Kobrin
Carol B
CB
Watson
Thelma M
TM
Frye
Andrea Robin
AR
Pennington
Robin
R
Harvey
Linda
L
Jaffe
Elaine S
ES
Robb
Richard J
RJ
Popescu
Mircea C
MC
Kwak
Larry W
LW
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D051798:Inhibitor of Differentiation Protein 1; D008081:Liposomes; D008224:Lymphoma, Follicular / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018448:Models, Immunological; D012074:Remission Induction; D012097:Repressor Proteins / Q000008:administration & dosage* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000008:administration & dosage* / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; C497453:ID1 protein, human; D007130:Immunoglobulin Idiotypes; D051798:Inhibitor of Differentiation Protein 1; D008081:Liposomes; D012097:Repressor Proteins; D014157:Transcription Factors