Anti-idiotype sera raised against surface immunoglobulin of human neoplastic lymphocytes.

Hough, David W.; Eady, R P; Hamblin, T.J.; Stevenson, F K; Stevenson, G T

doi:10.1084/jem.144.4.960

Cited by 45 publications

(20 citation statements)

References 29 publications

(33 reference statements)

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“…This may be Antibody therapy in cancer haematologica | 2014; 99 (10)defined 15 as a failure of immunological effectors to kill antibody-coated targets at antibody levels predicted to lie within the cytotoxic range. It implies a much more prolonged failure than a transient overwhelming of immunological capacity.…”

Section: Problem 3: Effector Modulationmentioning

confidence: 99%

Three major uncertainties in the antibody therapy of cancer

Stevenson

2014

Haematologica

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Antibodies against surface molecules of human tumors are now frequently administered in combination with strong chemotherapy, increasing therapeutic efficacy but making the task of elucidating immunological events more difficult. Experiments on genetically manipulated mice indicate that antibody efficacy is greatest when IgG antibody coating tumor cells is engaged by the Fcγ-receptors of effector cells, chiefly the monocyte/macrophage lineage. Evidence suggests lesser roles for NK cells, neutrophils, receptor-mediated cytotoxicity and complement-mediated cytotoxicity. The classical mode of killing employed by macrophages is phagocytosis, but much has to be learned about optimally activating macrophages for this task, and about any other modes of cytotoxicity used. There is renewed interest in antigenic modulation, which implies removal of therapeutic antibody linked with antigen from target-cell surfaces. It is now apparent that this removal of immune complexes can be achieved either by internalization by the target cell, or by transfer of the complexes to another cell by trogocytosis. In trials, anti-idiotype antibodies surprisingly proved therapeutically more effective than anti-CD20, despite anti-idiotype being more effectively removed from target-cell surfaces by antigenic modulation. This anomalous result might reflect the fact that persistence of anti-CD20 immune complexes in large amounts induces serious effector modulation, which paralyzes macrophage attacks on antibody-coated cells. The case for effector modulation is argued by analogy with the therapeutic suppression of autoimmune inflammation by effector modulation, achieved by infusion either of normal IgG in large amounts, or of anti-red cell IgG in relatively small amounts. ABSTRACTexamined for tumor Id. Very low levels were detected in all patients, but they all subsequently remained in remission and this has been maintained up to the time of writing; a striking example of tumor dormancy.Anti-Id therapy is now in abeyance due to the logistical difficulties involved in preparing individual antibodies for each patient. However, follicular lymphomas have been found to present an unusual glycan on their variable domains, close to the idiotypic epitopes, so there is a prospect that, for these tumors, an antibody of good affinity aimed at the glycan could be an effective single substitute for multiple anti-Id preparations.

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Section: Problem 3: Effector Modulationmentioning

confidence: 99%

Three major uncertainties in the antibody therapy of cancer

Stevenson

2014

Haematologica

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“…The generation of antisera with complement- and cell-mediated specific cytotoxic activity against lymphoma idiotype formed the basis for first attempts to treat malignant lymphomas by specific immunotherapy [36]. Administration of such antisera to patients with lymphocytic leukemia indeed resulted in a decrease in tumor cell mass, but the therapeutic effect was only transient [37].…”

Section: Immunology Of Nhlmentioning

confidence: 99%

Vaccination Strategies in the Treatment of Lymphomas

Veelken

Osterroth²

2002

Oncology

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Malignant lymphomas are clonal neoplasms of lymphoid origin. By definition, all cells of the malignant clone have undergone the same rearrangement of antigen receptor genes and express identical antigen receptor molecules (immunoglobulin for B cell lymphomas, T cell receptor for T cell lymphomas). The hypervariable stretches within the variable regions of these receptors are considered true tumor-specific antigens (‘idiotypes’). In several animal models, protective humoral or cellular immunity can be induced against the malignant lymphoma by vaccination with the tumor-derived idiotype. Successful experimental immunization strategies in animals include idiotype protein vaccines combined with various adjuvants, genetically or immunologically modified lymphoma cells, idiotype-presenting dendritic cells, idiotype-encoding viral vectors, and DNA immunization. Firm evidence for the induction of lymphoma-specific immunity has also been obtained from human idiotype vaccination trials. Furthermore, some trials have provided strong but hitherto formally unproven evidence for clinical benefit of idiotype-vaccinated patients. Alternative vaccination approaches are based on immunologically modified tumor cells. Current research efforts concentrate on the identification of the most efficacious vaccination route, on definitive proof of clinical efficacy, and on the development of convenient methods to manufacture individual idiotype vaccines.

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“…Antibody to the idiotypic determinants on B lymphocytic neoplasms reacts with 36 the neoplastic cells and with only a negligible proportion of normal lymphocytes (Stevenson & Stevenson, 1975;Hough et al, 1976;Haughton et al, 1978;Krolick et al, 1979). Raising the antibody is an individual requirement for each tumour.…”

mentioning

confidence: 99%

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

Hamblin¹,

Abdul-Ahad²,

Gordon³

et al. 1980

Br J Cancer

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134

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Tumour-specific antiserum was raised in sheep against idiotypic determinants on the surface immunoglobulin of neoplastic lymphocytes from a patient with chronic lymphocytic leukaemia (prolymphocytic variant). The complement-activating IgG1 subclass of the anti-idiotype was prepared from the serum in monodisperse form for infusion. Two treatments of 480 and 1200 mg caused the white-cell count to fall by one-third and one-half respectively. However, there was a rapid resurgence, so that by 8 days after each treatment the counts were restored to approximately 85% of their former levels. No change was noted in the size of spleen or lymph nodes. Each treatment probably destroyed 4-8 X 10(11) cells, some 10% of the total tumour load. The antibody was rapidly consumed, and there was evidence of heavy utilization of complement.

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Anti-idiotype sera raised against surface immunoglobulin of human neoplastic lymphocytes.

Cited by 45 publications

References 29 publications

Three major uncertainties in the antibody therapy of cancer

Three major uncertainties in the antibody therapy of cancer

Vaccination Strategies in the Treatment of Lymphomas

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

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