Vaccination of patients with B–cell lymphoma using autologous antigen–pulsed dendritic cells

Hsu, Frank J.; Benike, Claudia; Fagnoni, Francesco; Liles, Tina Marie; Czerwinski, Debra K.; Taidi, Behnaz; Engleman, Edgar G.; Levy, Ronald

doi:10.1038/nm0196-52

Cited by 1,677 publications

(940 citation statements)

References 33 publications

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“…cancer. 10,11 However, the outcome of the clinical therapeutics targeting these TAAs is not satisfactory. In lung carcinoma, no available TAAs to target have been identified.…”

Section: Anti-m2bp Antibody In Sera From Patients With Lung Carcinomamentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9] Some TAAs had been established as targets for cancer immunotherapy in several clinical trials. 10,11 Conversely, in lung carcinoma, no available cancer immunotherapy has been established. It is necessary to define novel TAAs which are highly expressed in cancer cells and can evoke a strong antitumor immune response in patients with lung carcinoma.…”

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confidence: 99%

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Expression and immunogenicity of a tumor‐associated antigen, 90K/Mac‐2 binding protein, in lung carcinoma

Ozaki

Kontani

Hanaoka³

et al. 2002

Cancer

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BACKGROUNDThe authors attempted to obtain shared proteins among lung carcinoma cells by column chromatographies. A glycoprotein with approximately 500 kDa isolated from QG56 cells showed an identical amino acid sequence to 90K/Mac‐2 binding protein (M2BP). This protein has been reported to be highly expressed and to modulate the expression of surface molecules involved in immune responses on cultured cancer cells. Therefore, it would be beneficial for M2BP to be targeted in cancer immunotherapy.METHODSThe authors analyzed the expression of M2BP in lung carcinoma cells and M2BP's immunogenicity as a tumor antigen. Eight cultured lung carcinoma cell lines and 28 tumor tissues from patients with lung carcinoma were examined for the expression of M2BP mRNA and protein. Sera from cancer patients (n = 23) and healthy donors (n = 19) were studied for their reactivity to M2BP peptides by enzyme–linked immunosorbent assay.RESULTSSeven of the 8 (87.5%) lung carcinoma cell lines and 17 of the 28 (60.7%) tumor tissues expressed high levels of M2BP mRNA. Most of the M2BP mRNA‐positive cancer cell lines and tumors also showed M2BP protein expression. The serum levels of antibodies to M2BP were elevated in 30.4% of the patients. In addition, M2BP‐specific immunoglobulin G was observed in all patients with anti‐M2BP antibodies.CONCLUSIONSM2BP is highly expressed in lung carcinoma cells and is sufficiently immunogenic to elicit specific immunity to this molecule in patients with lung carcinoma. M2BP is expected to be useful as a tumor marker and a target antigen in cancer immunotherapy. Cancer 2002;95:1954–62. © 2002 American Cancer Society.DOI 10.1002/cncr.10899

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“…cancer. 10,11 However, the outcome of the clinical therapeutics targeting these TAAs is not satisfactory. In lung carcinoma, no available TAAs to target have been identified.…”

Section: Anti-m2bp Antibody In Sera From Patients With Lung Carcinomamentioning

confidence: 99%

mentioning

confidence: 99%

Expression and immunogenicity of a tumor‐associated antigen, 90K/Mac‐2 binding protein, in lung carcinoma

Ozaki

Kontani

Hanaoka³

et al. 2002

Cancer

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“…Immune responses system is capable of recognizing tumor specific/ to id-Ig have been demonstrated in murine and human associated antigens, whereas the generation of an effec-B cell tumors. [11][12][13][14] One approach for the treatment of tive antitumor immune response is inefficient. Transfer CML and B-CLL would thus be to use irradiated and of genes encoding for cytokines or adhesion molecules cytokine/adhesion molecule gene transduced tumor cells into syngeneic/autologous tumor cells may therefore as vaccines to augment the in vivo host immune response enhance the presentation of tumor antigens to the to cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Efficient adenovirus-mediated gene transduction of normal and leukemic hematopoietic cells

et al. 1997

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We evaluated the efficiency of adenovirus-mediated gene targeted cells. A novel protocol for the efficient transduction transfer into normal and malignant human hematopoietic of adenovirus into B-CLL cells was presented. We showed cells. An E-1 and E-3 deleted, replication-defective recomthat anti-CD40 mAb or CD40 ligand acts in synergy with binant Ad.RSV␤gal vector was used and the transduction rhIL-4 to enable the transduction of approximately 50-75% efficiency was studied at a multiplicity of infection of 13 of B-CLL cells (B-CLL, n = 6). Expression of ␤-galactop.f.u. per cell. Approximately 40-50% of normal monocytes sidase in transduced CML cells and B-CLL cells was were transduced, whereas purified normal resting T cells detected for at least 15 days after transduction. The and B cells were resistant to infection. We showed that 50-present studies underline the utility of adenovirus vectors 80% of primary chronic myeloid leukemia cells (CML, n = for the construction of cytokine gene-modified tumor vac-12) were efficiently transduced. In contrast to CML, succines for the treatment of hematopoietic malignancies such cessful transduction of resting primary chronic B lymphoas CML and B-CLL. cytic leukemia cells required appropriate preactivation of for 3 days with rhGM-CSF (100 U/ml) before infection. Activation of cells with GM-CSF did not influence the (CD14 + , 90-98%) were readily transduced and stained transduction rate (data not shown). strongly positive for ␤-galactosidase (five separate experiments). Unlike the experience with retrovirus, we rhIL-4 together with hCD40 ligand are efficient and showed that efficient transduction of normal peripheral necessary for the transduction of primary B-CLL cells blood monocytes can be achieved with adenovirus withMononuclear cells from chronic B lymphocytic leukemia out preactivation of target cells. In contrast, purified (B-CLL, n = 6) patients were studied for adenoviral vector resting T lymphocytes (CD3 + , Ͼ96%) and B lymphocytes transduction. B-CLL cells were Ig-light chain restricted (CD19 + , Ͼ95%) were, however, not permissive to transand displayed CD5 (100%) and CD19 (80-95%) on the duction (three separate experiments).cell surface. Similarly to normal resting B lymphocytes (Figure 1), Efficient transduction of primary CML cells without resting primary B-CLL cells were resistant to adenovirus preactivation of target cells infection. A number of activation protocols [15][16][17][18] were Unselected mononuclear cells from chronic myeloid leutested to improve the transduction efficacy of B-CLL kemia patients (CML, n = 12) were included in the cells. We found that neither phorbol ester induction nor present studies. Although all the CML cells were Ph + , but the combination of SAC + thioredoxin + IL-2, forskolin represented heterogeneous cell populations. CML cells nor TNF␣ were efficient in improving the transduction expressed CD13 (40-80%), CD33 (40-81%) and other cell rate. In marked contrast, approximately 70-75% B-CLL surface markers (Table 1). No sign...

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“…22 Although all of these strategies are effective in inhibiting tumor growth in experimental animal models, all require the target cells to be removed from the body, manipulated ex vivo, and returned to the tumor-bearing donor/recipient. 21,23,25,26 We now demonstrate that intratumoral injection of Ad-mFL causes the rejection of transplanted hepa 1-6 hepatoma in a syngenic model. The Ad-mFL that was constructed and used in this experiment is highly efficient in infecting tumor cells both in vitro and in vivo.…”

Section: Systemic Splenocytes Adoptive Therapymentioning

confidence: 56%

Treatment of hepatocellular carcinoma with adenoviral vector-mediated Flt3 ligand gene therapy

et al. 2005

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Fms-like tyrosine kinase 3 ligand (Flt3L) plays an important role in development and activation of dendritic cells (DCs) and natural killer cells (NK). It has been shown that administration of either tumor cells transfected in vitro with Flt3L vectors or soluble Flt3L fusion protein in a high dose can enhance host antitumor immunity in animal model systems. In this study, we developed a recombinant defective adenovirus with an insert of gene encoding extracellular domain of mouse Flt3L (Ad-mFlt3L) under control of cytomegalovirus promoter and investigated its biological efficacy in eliciting tumor-specific immune response against hepatocellular carcinoma in mouse hepatoma model. The constructed Ad-mFlt3L efficiently infected hepa 1-6 hepatoma cells both in vitro and in vivo, leading to a high production of mFlt3L proteins in association with accumulation of DCsNK cells and lymphocytes in local tumor tissues. Tumor cells infected with Ad-mFlt3L lost tumorigenicity and became more immunogenic in syngeniec animal models. Intratumoral injection of Ad-mFlt3L (10 9 expression-forming unit) Â 3 significantly inhibited tumor growth with elicitation of long-lasting antitumor immunity, which is both preventive and curative. The tumor-specific immunity can be partially abrogated by depletion of either CD3 þ CD4 þ T cells or NK cells and can be also re-established in naïve animals by adoptive transfer of splenocytes from treated mice. The results suggest that adenovirus-mediated Flt3L gene therapy may provide a useful strategy for treatment of cancers.

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Vaccination of patients with B–cell lymphoma using autologous antigen–pulsed dendritic cells

Cited by 1,677 publications

References 33 publications

Expression and immunogenicity of a tumor‐associated antigen, 90K/Mac‐2 binding protein, in lung carcinoma

Expression and immunogenicity of a tumor‐associated antigen, 90K/Mac‐2 binding protein, in lung carcinoma

Efficient adenovirus-mediated gene transduction of normal and leukemic hematopoietic cells

Treatment of hepatocellular carcinoma with adenoviral vector-mediated Flt3 ligand gene therapy

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