Targeting of Antigens to Activated Dendritic Cells In vivo Cures Metastatic Melanoma in Mice

Abstract

Anti (A)-DEC-205 antibodies target to the DEC-205 receptor that mediates antigen presentation to T cells by dendritic cells. To exploit these properties for immunization purposes, we conjugated the melanoma antigen tyrosinase-related protein (TRP)-2 to ADEC-205 antibodies and immunized mice with these conjugates together with dendritic cell-activating oligonucleotides (CpG). Upon injection of the melanoma cell line B16, ADEC-TRP immunized mice were protected against tumor growth. Even more important for clinical applications, we were able to substantially slow the growth of implanted B16 cells by injection of ADEC-TRP2 conjugates into tumor bearing hosts. Approximately 70% of the animals were cured from existing tumors by treatment with ADEC conjugates carrying two different melanoma antigens (TRP-2 and gp100). This protection was due to induction of melanoma-specific CD4 and CD8 responses. Thus, these data show that targeting of dendritic cells in situ by the means of antibody-antigen conjugates may be a novel way to induce long-lasting antitumor immunity. (Cancer Res 2005; 65(15): 7007-12)

Selection of an Antibody Library Identifies a Pathway to Induce Immunity by Targeting CD36 on Steady-State CD8α+ Dendritic Cells

“…Indeed, a clear comparison of the long-term effects triggered by different receptors remains an open issue. The C-type lectin DEC205 has been the prototype DC target receptor to induce immune responses against various Ags (7,32,33). However, targeting DEC205 leads to tolerance unless a second maturation signal such as CD40L is provided (5).…”

“…In brief, 10 7 BMDCs or BO9 T cells were surface biotinylated (EZ-Link Sulfo-NHS-biotinylation kit) and lysed. Cell debris were spun out (12,000 rpm, 15 min) and supernatants were precleared with 10 g of anti-SV5tag mAb (20) and 200 l of 50% protein A-Sepharose CL-4B beads (Amersham Biosciences) for 2 h at 4°C.…”

Antibody-targeted vaccines

“…Furthermore, administration of this ATV 1 week posttumor challenge resulted in a more significant delay of tumor progression compared to other popular methods of vaccinating. Mahnke et al (2005) developed DEC-205 targeted ATVs with the melanoma antigen tyrosinase-related protein-2 and used a vaccination strategy combined with cytosine-guanosine oligonucleotide (CpG) oligodeoxynucleotides to investigate the effect on tumor challenge with the melanoma cell line B16. The DEC-205-targeted vaccination protected mice against tumor growth and substantially slowed the growth of previously implanted B16 cells.…”

Vaccination with filamentous bacteriophages targeting DEC‐205 induces DC maturation and potent anti‐tumor T‐cell responses in the absence of adjuvants

“…The anti-DEC-205 mAb has been used to deliver antigens to DCs. While delivering DEC-205 targeted antigen in conjugation with DC activation/maturation agents (such as anti-CD40 mAb, poly I:C and LPS) has been reported to result in a potent immune response [6][7][8][9][10][11][12], targeting DEC-205 in the absence of such maturation signals has been described to result in T-cell tolerance [13][14][15]. The development of vaccines able to access DCs, thereby eliciting more efficient immune responses, is one of the aims of immune therapy starting from the recent past [16,17].…”