Human anti-idiotypic antibodies induced a humoral and cellular immune response against a colorectal carcinoma-associated antigen in patients.

Fagerberg, Jan; Wigzell, Hans; Askelöf, Per; Mellstedt, Håkan

doi:10.1073/pnas.92.11.4773

Cited by 77 publications

(40 citation statements)

References 18 publications

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“…The same pattern of expression has been described for the panepithelial glycoprotein EGP of the mouse and the human epithelial glycoprotein antigen/major gastrointestinal tumor-associated protein GA733-2/EGP314 (Bergsagel et al, 1992;Momburg et al, 1987;Zaloudik et al, 1997). Since expression of GA733-2/EGP314 is used as diagnostic and therapeutic tool (Fagerberg et al, 1995;Li et al, 1997), it was of interest to evaluate, whether D5.7A is, indeed, the rat ortholog, which would o er a possibility to elaborate functional activities of the molecule.…”

Section: Resultsmentioning

confidence: 63%

Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314

Würfel

Rösel

Seiter³

et al. 1999

Oncogene

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Screening for surface molecules expressed by metastasizing rat tumors had revealed evidence for metastasisassociation of a molecule also expressed on epithelial cells. The similarity to the expression pro®le of the panepithelial glycoprotein EGP314 prompted us to isolate and sequence the gene and to explore functional features of the molecule in transfected tumor lines. The molecule D5.7A, named according to the antibody, D5.7, used for selection, indeed, is the ortholog of EGP314 with 92% and 80% identity to the murine and the human molecules. Like EGP314, D5.7A has a particular cleavage site, a small cleavage product being resolved under reducing conditions from the membrane anchored part of the molecule. Transfection of a low metastasizing ®brosarcoma, pheochromoblastoma and adenocarcinoma revealed that expression of D5.7A facilitates tumor progression. Depending on the origin of the tumor, D5.7A transfectants either metastasized via the lymphatic system (pheochromoblastoma, adenocarcinoma) or hematogeneously (®brosarcoma). Particularly after proteolytic cleavage, D5.7A facilitated cell ± cell adhesion and provided a proliferative signal upon crosslinking. Thus, the rat ortholog of EGP314 is involved in metastasis formation. Importantly, its functional activities apparently rely on proteolytic cleavage. These ®ndings provide a ®rst evidence on how a panepithelial marker can be involved in tumor progression.

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Section: Resultsmentioning

confidence: 63%

Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314

Würfel

Rösel

Seiter³

et al. 1999

Oncogene

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“…Details of the assay have been previously described in detail (18,19). Briefly, peripheral blood mononuclear cells (PBMC) were stimulated with purified F(ab ¶) 2 fragments of the autologous monoclonal IgG (1 pg/mL to 100 Ag/mL) and polyclonal IgG (Octapharma AB, Stockholm, Sweden) as well as with three allogeneic monoclonal isotype-matched IgG F(ab ¶) 2 fragments (purified from other myeloma patients) and cultured for 6 days.…”

Section: Methodsmentioning

confidence: 99%

Long-term Idiotype Vaccination Combined with Interleukin-12 (IL-12), or IL-12 and Granulocyte Macrophage Colony-Stimulating Factor, in Early-Stage Multiple Myeloma Patients

Hansson

Abdalla

Moshfegh

et al. 2007

Clinical Cancer Research

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Purpose and Experimental Design: Twenty-eight patients with immunoglobulin G myeloma stages I to II were immunized i.d. over 110 weeks with autologous M protein combined with interleukin-12 (IL-12; n = 15) or with IL-12 and granulocyte macrophage colony-stimulating factor (GM-CSF; n = 13). Idiotype-specific T-cell responses were assessed by [ 3 H]thymidine incorporation, enzyme-linked immunospot assay, and delayed-type hypersensitivity reaction. Results: Based on these three assays, idiotype-specific immune responses were noted in 5 of 15 (33%) patients in the IL-12 group and in 11 of 13 (85%) patients in the GM-CSF/IL-12 group (P < 0.01). Immune response was seen only in patients with M-component concentration of <50 g/L. Three of 16 (19%) responders showed a gradually increasing idiotype-specific T-cell response, whereas 11 of 16 (69%) patients showed initial response, which then disappeared rapidly; the latter pattern was frequently associated with subsequent progressive disease. Immune nonresponse was associated with an increase in the numbers of CD4 + /CD25 + cells (regulatory T cells), which was absent in responding patients. Median time to progression for immune responders (n = 16) was 108 weeks compared with 26 weeks for nonresponders (n = 12; P = 0.03). Conclusions: These results indicate that idiotype immunization of myeloma patients with GM-CSF and IL-12 may induce specific T-cell response more frequently than with IL-12 alone and that immune response may correlate with time to progression and nonresponse with increased numbers of regulatory T cells.

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“…Counts per minute (cpm) of the irradiated B cells were subtracted from the T-cell count. For each individual, the highest SI value obtained from the T/B ratio concentration curve is shown, as well as the T/B cell ratio concentration curve (Fagerberg et al, 1995). As background controls, normal control T cells stimulated with activated autologous B cells, as well as autologous T cells stimulated with non-activated leukaemic B cells were used.…”

Section: Activation Of B Cellsmentioning

confidence: 99%

Autologous T lymphocytes may specifically recognize leukaemic B cells in patients with chronic lymphocytic leukaemia

et al. 2000

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Summary. This study analysed a naturally occurring specific cellular immunity against tumour cells in chronic lymphocytic leukaemia (CLL) patients. Five out of eight patients had blood T lymphocytes able to recognize spontaneously and specifically the autologous tumour B cells (proliferation assay). In these five patients, detection of cytokines by realtime reverse transcription polymerase chain reaction (RT-PCR) revealed that granulocyte±macrophage colony-stimulating factor (GM-CSF) was the most abundant cytokine gene expressed by the T cells that recognized the autologous tumour B cells. Other activated cytokine genes were ginterferon (IFN), interleukin (IL)-2 and tumour necrosis factor (TNF)-a, but not IL-4. This profile suggests a type 1 anti-B-CLL T-cell response. CD80 and CD54 were relatively downregulated on the native tumour B cells compared with control normal B cells. Upregulation of CD80 on the leukaemic cells was mandatory for the induction of such a specific T-cell response. CD80 and CD54 monoclonal antibodies inhibited the specific T-cell DNA synthesis proliferation. The proliferative T-cell response was either MHC class I or class II restricted (inhibition by monoclonal antibodies). The specific cytokine gene expression could be found in isolated CD4, as well as CD8, T-cell subsets. This study demonstrated the presence of a potential natural specific CD4, as well as a CD8 type 1 T-cell immunity against the leukaemic CLL tumour B cells in CLL. A further detailed analysis of the spontaneous anti-CLL T-cell immunity is warranted that may facilitate the development of effective anti-tumour vaccines in CLL.

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Human anti-idiotypic antibodies induced a humoral and cellular immune response against a colorectal carcinoma-associated antigen in patients.

Abstract: Induction of immunity against antigens expressed on tumor cells might prevent or delay recurrence of the disease. Six patients operated on for colorectal carcinoma were immunized with human monoclonal anti-idiotypic anti-

Cited by 77 publications

References 18 publications

Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314

Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314

Long-term Idiotype Vaccination Combined with Interleukin-12 (IL-12), or IL-12 and Granulocyte Macrophage Colony-Stimulating Factor, in Early-Stage Multiple Myeloma Patients

Autologous T lymphocytes may specifically recognize leukaemic B cells in patients with chronic lymphocytic leukaemia

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