Immunogenicity of allo-vesicle carrying ERBB2 tumor antigen for dendritic cell-based anti-tumor immunotherapy.
Dendritic cells (DCs) are able to orchestrate innate and acquired immunity and can activate and sustain a long-lasting anti-tumor immune response in vivo when used as anti-tumor cell therapy. The selection of the antigen and the choice of its formulation are key points in designing anti-cancer DC-based vaccines. Cell released vesicles/exosomes have been shown to transfer antigens, HLAI/peptide complexes and co-stimulatory molecules to recipient cells. In this study we describe the generation of an allogenic microvesicle cell factory in which the expression of a specific tumor antigen was combined to the expression of co-stimulatory and allogeneic molecules. The DG75 lymphoblastoid cell line was selected as microvesicle producer and transfected with ErbB2, as tumor antigen prototype. The shed microvesicles transferred antigenic components to recipient DCs, increasing their immunogenicity. DC pulsing resulted in cross-presentation of ErbB2 both in HLAI and HLAII compartments, and ErbB2-specific CD8+ T cells from cancer patients were activated by DCs pulsed with vesicle-bound ErbB2. The microvesicle cell factory proposed may represent a source of cell free immunogen to be used for DC-based cancer therapy.
Napoletano
C
C
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Rughetti
A
A
Landi
R
R
Pinto
D
D
Bellati
F
F
Rahimi
H
H
Spinelli
G P
GP
Pauselli
S
S
Sale
P
P
Dolo
V
V
De Lorenzo
F
F
Tomao
F
F
Benedetti-Panici
P
P
Frati
L
L
Nuti
M
M
D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D022161:Transport Vesicles / Q000276:immunology / Q000637:transplantation*
D000951:Antigens, Neoplasm; D006680:HLA Antigens; D007371:Interferon-gamma; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human