Preliminary experience in treating lymphocytic leukaemia with antibody to immunoglobulin idiotypes on the cell surfaces

Hamblin, T.J.; Abdul-Ahad, A K; Gordon, J; Stevenson, F K; Stevenson, G T

doi:10.1038/bjc.1980.271

Cited by 134 publications

(25 citation statements)

References 24 publications

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“…The first attempts to use a defined antibody to treat human B cell malignancy was with anti-Id antibody (39,40), which remains an effective strategy. The problem is that each Id Ig is different, and it is expensive and technically demanding to make individual anti-Id antibodies.…”

Section: Dna Fusion Gene Vaccines Against B Cell Malignanciesmentioning

confidence: 99%

DNA vaccines to attack cancer

Stevenson

Ottensmeier

Johnson

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

111

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Delivery of antigens by injection of the encoding DNA allows access to multiple antigen-presenting pathways. Knowledge of immunological processes can therefore be used to modify construct design to induce selected effector functions. Expression can be directed to specific intracellular sites, and additional genes can be fused or codelivered to amplify responses. Therapeutic vaccination against cancer adds a requirement to overcome tolerance and to activate a weakened immune repertoire. Induction of CD4 ؉ T helper cells is critical for both antibody and T cell effector responses. To activate immunity against tumor antigens, we fused the tumor-derived sequences to genes encoding microbial proteins. This strategy engages T helper cells from the large antimicrobial repertoire for linked help for inducing antibody against cell-surface tumor antigens. The principle of linked T cell help also holds for induction of epitope-specific antitumor CD8 ؉ T cells, but the microbial sequence has to be minimized to avoid competition with tumor antigens. Epitope-specific DNA vaccination leads to powerful antitumor attack and can activate immunity from a profoundly tolerized repertoire. Vaccine designs validated in preclinical models are now in clinical trial with immune responses detected against both tumor antigens and fused microbial antigens. DNA priming is highly efficient, but boosting may benefit from increased antigen expression. Physical methods including electroporation provide increased expression without introducing additional competing antigens. A wide range of cancers can be targeted, and objective assays of response will determine efficacy.

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Section: Dna Fusion Gene Vaccines Against B Cell Malignanciesmentioning

confidence: 99%

DNA vaccines to attack cancer

Stevenson

Ottensmeier

Johnson

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

111

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“…Unfortunately it remains a significant stumbling block in RIT. In B cell tumours, where the labelled antibody is commonly directed against the idiotype of the antibody secreted by the tumour cell, some reduction in circulating antigen (lymphoma-secreted antibody) can be obtained by plasmaphoresis, but the reduction is short-lived (Hamblin et al, 1980;Meeker et al, 1985).…”

Section: Carriermentioning

confidence: 99%

Radioimmunotherapy of malignancy using antibody targeted radionuclides

Cobb¹,

Humm²

1986

Br J Cancer

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Summary Antibodies directed against tumour associated antigens provide a means for delivering preferentially cytotoxic radionuclides to the cells of primary and secondary tumours. The factors that influence the effectiveness of the radiation in the tumour compared with its effect on the radiosensitive normal tissues include the specificity of the antibody, the distribution of targeted energy within the tumour and the host's response to the injected foreign antibody. Recently some encouraging results from clinical trials of radioimmunotherapy have been reported in the literature. There is a continual search for more avid and specific antibodies, and the techniques of genetic engineering are being applied to the problem of reducing the antigenicity and mass of the carrier antibody. The improved efficiency of the labelled antibody needs to be supplemented by an identification of those tumours most likely to respond to this form of therapy.

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“…Drug and X-ray treatment of A31 The 2 groups of control non-treatment mice inoculated with 105 A3 1 s.c. died with median survival times of 35 and 36 days (Table II) (Hamblin et al, 1980) or other workers (Rankin et al, 1985). A number of research groups are examining closely the part that anti-idiotype antibodies may play in the therapy of lymphoma used alone , with attached drugs and toxins (Gilliland et al, 1980;Embleton et al, 1983), or carrying cellsterilising amounts of radionuclides (Larsen et al, 1983).…”

Section: Cytogenetic Preparationsmentioning

confidence: 99%

Characterisation of a new murine B cell lymphoma

Cobb¹,

Glennie²,

McBride³

et al. 1986

Br J Cancer

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The characterisation of a new murine B cell lymphoma, A31, is described. Histopathological examination of passaged tumour indicates that initial infiltration occurs in the spleen, lymph nodes, Peyer's patches and liver, while in the terminal phase the bone marrow, gonads and occasionally the central nervous system become involved. The terminal spread is coincidental with the leukaemic phase in the tumour. The tumour cells show typical B cell characteristics in vitro. These include surface immunoglobulin (Ig) of mu, kappa isotype, surface Ia, Thy-1 negativity and an increased uptake of tritiated thymidine following incubation with lipopolysaccharide. A31 cells secrete low levels of IgM into the tissue culture fluid. Short-term culture produced only 100 ng IgM per 10(7) cells over 8 h and no tumour-associated monoclonal band could be detected in the serum of tumour-bearing mice. Chromosomal karyotypes of A31 cells gave model numbers 2n=40 normal, and 2n=41, with partial trisomy of chromosome 2, and trisomy of 17. There was loss of a chromosome 6 and the Y chromosome, together with the translocation of part of an 11 to one of the two unidentified marker chromosomes. The responses of lymphoma-bearing mice to therapeutic levels of cyclophosphamide and vincristine sulphate and also to whole body X-radiation are illustrated. This tumour may help in unravelling the complex biology of B cell lymphoma and because of its low level of Ig secretion, be of particular value in experimental immunotherapy. Images Figure 1 Figure 5

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Preliminary experience in treating lymphocytic leukaemia with antibody to immunoglobulin idiotypes on the cell surfaces

Cited by 134 publications

References 24 publications

DNA vaccines to attack cancer

DNA vaccines to attack cancer

Radioimmunotherapy of malignancy using antibody targeted radionuclides

Characterisation of a new murine B cell lymphoma

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