Cell-free tumor antigen peptide-based cancer vaccines

Schmidt, W.; Buschle, Michael; Zauner, Wolfgang; Kirlappos, Helen; Mechtler, Karl; Trska, Barbara; Birnstiel, Max L.

doi:10.1073/pnas.94.7.3262

Cited by 53 publications

(29 citation statements)

References 51 publications

(45 reference statements)

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“…Even if applied in an optimized formulation, a combination of immunodominant melanoma Ag was less potent in inducing systemic antitumor immunity than cellular vaccines consisting of irradiated IL-2-or GM-CSF-secreting tumor variants. 32 The efficiency of peptide vaccines may be improved as soon as more immunodominant peptides have been identified and their introduction in the host Ag-presenting system is optimized.…”

Section: Resultsmentioning

confidence: 99%

Potential of CD80-transfected human breast carcinoma cells to induce peptide-specific T lymphocytes in an allogeneic human histocompatibility leukocyte antigens (HLA)-A2.1+-matched situation

et al. 1999

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Allogeneic human histocompatibility leukocyte antigen (HLA)-matched tumor cell lines that have been made immunogenic by the transfer of genes encoding for costimulatory molecules such as CD80 are considered to be potential vaccines for the induction of systemic immune reactions in cancer patients. We used a human HLA-A2.1 ϩ CD80-transfected breast carcinoma cell line (KS-CD80) and investigated in vitro the efficiency at which antigen (Ag)-specific responses were induced following the stimulation of allogeneic HLA-A2.1-matched T lymphocytes. The influenza matrix protein M1 was used as a model Ag. It was either endogenously expressed or exogenously loaded as a peptide (matrix protein), and the frequency of the generated specific T cells was determined. The expression of CD80 in KS cells was required for an effective activation and expansion of Ag-specific T cells. This response was augmented following the pretreatment of KS-CD80 cells with interferon-␥ and tumor necrosis factor-␣. Interleukin-4 (IL-4), IL-7, and IL-12 further increased T-cell expansion. IL-7 was best at supporting the generation of T cells with Ag specificity. This investigation demonstrates that allogeneic CD80 ϩ tumor cells can induce Ag-specific, HLA-restricted T lymphocytes at a high frequency. Our study supports the use of allogeneic cell lines for the induction of specific T-cell responses in tumor patients.

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Section: Resultsmentioning

confidence: 99%

Potential of CD80-transfected human breast carcinoma cells to induce peptide-specific T lymphocytes in an allogeneic human histocompatibility leukocyte antigens (HLA)-A2.1+-matched situation

et al. 1999

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“…Local administration of Imiquimod induces a Th1-conducive cytokine storm that includes IFN-␣, TNF-␣, IL-1␣, IL-6, and IL-8 (28 -30), and causes the emigration of resident Langerhans cells from the treated site (31). Poly-arg was shown to enhance the immunogenicity and anticancer activities of peptide Ags (32,33). Fig.…”

Section: Immature DC Injected Into Adjuvant-treated Skin Acquire Migrmentioning

confidence: 99%

Injection of Immature Dendritic Cells into Adjuvant-Treated Skin Obviates the Need for Ex Vivo Maturation

Nair¹,

McLaughlin²,

Weizer

et al. 2003

The Journal of Immunology

153

115

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A key and limiting step in the process of generating human monocyte-derived dendritic cells (DC) for clinical applications is maturation. In the setting of immunotherapy, DC are matured ex vivo by culturing them with various agents that mimic the conditions encountered at a site of inflammation. This study examined whether the ex vivo DC maturation step could be replaced by maturing DC in situ by injecting immature DC into sites pre-exposed to agents that induce a microenvironment conducive to in situ maturation of the injected DC. The hypothesis was that recapitulation of the physiological conditions occurring during pathogen infection would lead to optimal conditions for DC maturation, migration, and function. Murine immature DC injected into adjuvant (Adjuprime, poly-arginine, or Imiquimod)-pretreated skin exhibited lymph node migratory capacity comparable to and immunostimulatory capacity equal to or exceeding that of ex vivo matured DC. Acquisition of migratory capacity did not always correlate with enhanced immunostimulatory capacity. Immunostimulatory capacity was not enhanced when mature DC were injected into adjuvant-pretreated sites and remained below that seen with immature DC matured in situ. Immature DC injected into adjuvant-pretreated sites were more effective than mature DC in stimulating antitumor immunity in mice. 111Indium-labeled human monocyte-derived immature DC injected into adjuvant (Imiquimod)-pretreated sites in cancer patients acquired lymph node migratory capacity comparable to ex vivo matured DC. This study shows that in situ maturation offers a simpler and potentially superior method to generate potent immunostimulatory DC for clinical immunotherapy.

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“…It has been shown that a complex mixture of tumor peptides conjugated to beads can prime a CTL response in healthy individuals (3), and lipid compounds have been reported to have adjuvant qualities (4). Yet, the most common adjuvant of T cell responses used to date is IFA.…”

mentioning

confidence: 99%

Cancer Vaccine Design: A Novel Bacterial Adjuvant for Peptide-Specific CTL Induction

Miconnet

Coste

Beermann

et al. 2001

The Journal of Immunology

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The recent identification of tumor Ags as potential vaccines has prompted the search for efficient adjuvants and delivery systems, especially in the case of peptide-based vaccination protocols. Here, we investigated the adjuvant potential of the recombinant 40-kDa outer membrane protein of Klebsellia pneumoniae (P40) for specific CTL induction. We studied the CTL response induced in HLA-A*0201/Kb transgenic mice immunized with peptides derived from two melanoma-associated differentiation Ags, the HLA-A*0201-restricted decapeptide Melan-A26–35 substituted at position 2 and the Kb-restricted tyrosinase-related protein 2181–188 T cell epitope. We found that both peptides are able to generate a specific CTL response when mixed with the protein in the absence of conventional adjuvant. This CTL response is a function of the amount of P40 used for immunization. Moreover, the CTL response generated against the tyrosinase-related protein 2181–188 peptide in presence of P40 is associated with tumor protection in two different experimental models and is independent of the presence of CD4+ T lymphocytes. Thus, the recombinant bacterial protein P40 functions as a potent immunological adjuvant for specific CTL induction.

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Cell-free tumor antigen peptide-based cancer vaccines

Cited by 53 publications

References 51 publications

Potential of CD80-transfected human breast carcinoma cells to induce peptide-specific T lymphocytes in an allogeneic human histocompatibility leukocyte antigens (HLA)-A2.1+-matched situation

Potential of CD80-transfected human breast carcinoma cells to induce peptide-specific T lymphocytes in an allogeneic human histocompatibility leukocyte antigens (HLA)-A2.1+-matched situation

Injection of Immature Dendritic Cells into Adjuvant-Treated Skin Obviates the Need for Ex Vivo Maturation

Cancer Vaccine Design: A Novel Bacterial Adjuvant for Peptide-Specific CTL Induction

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