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Frontiers in Immunology 2019The promise of idiotype-based therapeutics has been disappointing forcing a new look at the concept and its potential to generate an effective approach for... (Review)
Review
The promise of idiotype-based therapeutics has been disappointing forcing a new look at the concept and its potential to generate an effective approach for immunotherapy. Here, the idiotype network theory is revisited with regard to the development of efficacious anti-idiotype vaccines. The experience of polyclonal anti-Idiotype reagents in animal models as well as an understanding of the immune response in humans lends to the proposition that polyclonal anti-Idiotype vaccines will be more effective compared to monoclonal-based anti-Idiotype vaccines. This novel strategy can be adapted in Biotech-standard production of therapeutic antibodies.
Topics: Animals; Antibodies, Anti-Idiotypic; Biomarkers; Humans; Immunoglobulin Idiotypes; Immunomodulation; Immunotherapy; Protein Binding; Treatment Outcome; Vaccines
PubMed: 31031777
DOI: 10.3389/fimmu.2019.00808 -
Yonsei Medical Journal Feb 2007The unique antigenic determinants (Idiotype [Id]) of the immunoglobulin expressed on a given B-cell malignancy can serve as a tumor-specific antigen for active... (Review)
Review
The unique antigenic determinants (Idiotype [Id]) of the immunoglobulin expressed on a given B-cell malignancy can serve as a tumor-specific antigen for active immunotherapy. Therapeutic vaccines targeting the tumor-specific idiotype have demonstrated promising results against lymphomas in phase I/II studies and are currently being evaluated in phase III randomized trials. Additional vaccine therapies being developed include those based on DNA, dendritic cells, gene-modified tumor cells. It is hoped that immunotherapeutic agents, used in tandem or in combination, may in the future allow effective treatment of lymphoid malignancies and delay or even replace the need for conventional cytotoxic therapies.
Topics: Cancer Vaccines; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Immunoglobulin Idiotypes; Immunotherapy; Lymphoma
PubMed: 17326239
DOI: 10.3349/ymj.2007.48.1.1 -
Trends in Biotechnology Sep 2022There is an increasing demand for rapid, affordable, in-field screening methods for low molecular weight (LMW) compound detection. Anti-idiotypes (Ab2s) are biologically... (Review)
Review
There is an increasing demand for rapid, affordable, in-field screening methods for low molecular weight (LMW) compound detection. Anti-idiotypes (Ab2s) are biologically derived surrogates that can replace LMW compounds and their protein conjugates in immunoassays. Substitution with anti-idiotypes can improve assay standardisation, reduce cost, and contribute to environmental safety. Their application has been limited by difficult generation processes and varied effects on assay performance. This review examines a recent resurgence in the use of Ab2s within LMW compound detection, driven by the application of phage display and nanobodies. The methods used for Ab2 production are critically discussed and their potential role in improving LMW compound immunoassays is highlighted. Finally, forward-looking ideas for the production of anti-idiotypes are provided, along with barriers to their generation.
Topics: Immunoassay; Immunoglobulin Idiotypes; Molecular Weight
PubMed: 35317925
DOI: 10.1016/j.tibtech.2022.02.008 -
Human Vaccines & Immunotherapeutics May 2013The idiotype of B-cell non-Hodgkin lymphomas has been intensively investigated for its proven immunogenicity as a promising cancer vaccine. Indeed, available data... (Review)
Review
The idiotype of B-cell non-Hodgkin lymphomas has been intensively investigated for its proven immunogenicity as a promising cancer vaccine. Indeed, available data clearly indicate that these vaccines are able to induce tumor-specific immune responses and molecular remissions in patients with follicular lymphoma. However, only one of the three phase III trials performed so far demonstrated a prolonged disease-free survival in vaccinated patients. The observed failures have been mainly ascribed to defects in the study design and not to the limited efficacy of idiotype vaccines per se. Therefore, innovative and optimized idiotype-based vaccine formulations are being developed in order to overcome current limitations and improve the clinical benefit of this immunotherapeutic strategy. Among the most promising advances, the development of "off-the-shelf" vaccines appears of particular relevance, being potentially able to overcome the limitations related to the complex, time-consuming and expensive production of the individualized idiotypic vaccines currently used. Moreover, there is a pressing need to identify biomarkers suitable for the identification of the subset of patients who are most likely to benefit from vaccination. Recent findings also indicate that idiotypic vaccines may be safely and successfully used in additional clinical settings, including lymphoma patients after high-dose chemotherapy and autologous stem cell transplantation.
Topics: Cancer Vaccines; Clinical Trials as Topic; Disease-Free Survival; Humans; Immunoglobulin Idiotypes; Lymphoma, B-Cell; Vaccination
PubMed: 23406835
DOI: 10.4161/hv.23970 -
Nature Reviews. Cancer Sep 2009The clonal immunoglobulin idiotype displayed on the surface of most malignant B cells is a patient- and tumour-specific antigen that can be used for therapeutic... (Review)
Review
The clonal immunoglobulin idiotype displayed on the surface of most malignant B cells is a patient- and tumour-specific antigen that can be used for therapeutic vaccination. Several studies have confirmed the biological efficacy of soluble protein idiotypic vaccination and two clinical trials have shown the clinical efficacy of this procedure. One study has demonstrated clinical benefit associated with idiotypic vaccination. However, three randomized clinical trials have recently failed to achieve their main end points for reasons that are probably unrelated to the vaccine. While scepticism towards this type of non-toxic medical intervention is mounting, such patient-specific treatments might yet see the light of day through better designed clinical trials.
Topics: Cancer Vaccines; Clinical Trials as Topic; Humans; Immunoglobulin Idiotypes; Lymphoma
PubMed: 19701243
DOI: 10.1038/nrc2717 -
Cytotechnology 1997Dendritic cells (DC) are extremely potent antigen presenting cells, uniquely capable of sensitizing naive T cells to protein antigens and eliciting antigen specific... (Review)
Review
Dendritic cells (DC) are extremely potent antigen presenting cells, uniquely capable of sensitizing naive T cells to protein antigens and eliciting antigen specific immune responses. Studies of human DC isolated from peripheral blood indicate that these cells can be used to stimulate and expand antigen specific CD4+ and CD8+ T cells, in vitro. On the basis of these findings we have initiated pilot clinical studies to investigate the ability of DC pulsed ex vivo with tumor associated proteins to stimulate host anti-tumor immunity when re-infused as a vaccine. In the first such study DC pulsed with tumor derived idiotype protein were infused into patients with low grade malignant B cell lymphoma who had failed conventional chemotherapy. The majority of treated patients developed T cell mediated anti-idiotype immune responses and some of the patients experienced tumor regression. These results suggest that DC based immunotherapy is a potentially useful approach to B cell lymphoma and raises the possibility that the approach may prove useful in the treatment of other tumors as well.
Topics: Animals; Antigen Presentation; Antigens, Neoplasm; Dendritic Cells; Humans; Immunoglobulin Idiotypes; Immunotherapy; Lymphoma, B-Cell; Pilot Projects
PubMed: 9474803
DOI: 10.1023/a:1007997918593 -
Fertility and Sterility Feb 2009Sperm immunity in females can reduce the likelihood of natural conception, and sperm antibodies from female sera have been shown to inhibit IVF in humans and in several... (Review)
Review
Sperm immunity in females can reduce the likelihood of natural conception, and sperm antibodies from female sera have been shown to inhibit IVF in humans and in several animal models. The etiology of sperm immunity in human females is unknown, but several possible mechanisms have been proposed, including cross-reactivity with microbial antigens and interferon gamma-mediated potentiation of the antisperm immune response in women whose male partners have sperm autoantibodies in their semen. This article reviews these ideas and postulates a novel hypothesis based on the potential for the generation of anti-idiotype antibodies in women whose partners have sperm antibodies in their semen.
Topics: Antibodies; Antibody Specificity; Autoantibodies; Female; Fertilization in Vitro; History, 20th Century; Humans; Immunoglobulin Idiotypes; Infertility, Female; Interferon-gamma; Male; Risk Factors; Semen; Spermatozoa; Treatment Failure
PubMed: 18281044
DOI: 10.1016/j.fertnstert.2007.11.045 -
Current Pharmaceutical Design Jan 2010After twenty years of use in humans, customized idiotypic vaccination yet remains a non-approved, experimental therapeutic option for patients with lymphoma and myeloma.... (Review)
Review
After twenty years of use in humans, customized idiotypic vaccination yet remains a non-approved, experimental therapeutic option for patients with lymphoma and myeloma. Potentially applicable to all B-cell malignancies whose cells express a clonal immunoglobulin or its epitopes on their surface, this treatment is designed to prevent disease recurrence or progression. Mostly used in follicular lymphoma patients so far, idiotype vaccines have clearly shown biological efficacy, clinical efficacy and clinical benefit in this setting, although no study aiming at regulatory approval of the procedure has been able to meet its main clinical endpoints. In mantle cell lymphoma, only biological efficacy has been proven for idiotypic vaccination, while in multiple myeloma a limited number of studies support the notion of biological and perhaps even clinical efficacy, although no credible evidence of clinical benefit has still emerged. Idiotype vaccines have been produced and administered in a number of substantially different manners. Therefore, the results of most clinical trials cannot be easily compared, and even less pooled together in meaningful meta-analyses. A more creative and yet scientifically sound way to design clinical trials of customized active immunotherapies will be key to the future development of idiotype vaccines, particularly considering that we currently lack any clinical or biological indicator to possibly predict which patients are more likely to respond to idiotypic vaccination from an immunologic point of view. This review aims at summarizing the multifaceted success achieved by idiotype vaccines, as well as at outlining the challenges awaiting them in the near future: how to improve feasibility, immunogenicity and efficacy, as well as how to confirm benefit and gain regulatory approval.
Topics: Cancer Vaccines; Clinical Trials as Topic; Epitopes; Humans; Immunoglobulin Idiotypes; Lymphoma, Non-Hodgkin; Multiple Myeloma
PubMed: 20109139
DOI: 10.2174/138161210790170111 -
Frontiers in Immunology 2024Immune responses to both SARS-CoV-2 infection and its associated vaccines have been highly variable within the general population. The increasing evidence of... (Review)
Review
Immune responses to both SARS-CoV-2 infection and its associated vaccines have been highly variable within the general population. The increasing evidence of long-lasting symptoms after resolution of infection, called post-acute sequelae of COVID-19 (PASC) or "Long COVID," suggests that immune-mediated mechanisms are at play. Closely related endemic common human coronaviruses (hCoV) can induce pre-existing and potentially cross-reactive immunity, which can then affect primary SARS-CoV-2 infection, as well as vaccination responses. The influence of pre-existing immunity from these hCoVs, as well as responses generated from original CoV2 strains or vaccines on the development of new high-affinity responses to CoV2 antigenic viral variants, needs to be better understood given the need for continuous vaccine adaptation and application in the population. Due in part to thymic involution, normal aging is associated with reduced naïve T cell compartments and impaired primary antigen responsiveness, resulting in a reliance on the pre-existing cross-reactive memory cell pool which may be of lower affinity, restricted in diversity, or of shorter duration. These effects can also be mediated by the presence of down-regulatory anti-idiotype responses which also increase in aging. Given the tremendous heterogeneity of clinical data, utilization of preclinical models offers the greatest ability to assess immune responses under a controlled setting. These models should now involve prior antigen/viral exposure combined with incorporation of modifying factors such as age on immune responses and effects. This will also allow for mechanistic dissection and understanding of the different immune pathways involved in both SARS-CoV-2 pathogen and potential vaccine responses over time and how pre-existing memory responses, including potential anti-idiotype responses, can affect efficacy as well as potential off-target effects in different tissues as well as modeling PASC.
Topics: Humans; COVID-19; Post-Acute COVID-19 Syndrome; SARS-CoV-2; Vaccines; Aging; Immunoglobulin Idiotypes
PubMed: 38469293
DOI: 10.3389/fimmu.2024.1345499 -
Annals of Oncology : Official Journal... Feb 1991Human follicular lymphoma can be viewed as a malignancy in evolution. Since this disease is composed of a clonal population of B lymphocytes all expressing a given... (Review)
Review
Human follicular lymphoma can be viewed as a malignancy in evolution. Since this disease is composed of a clonal population of B lymphocytes all expressing a given immunoglobulin light chain and heavy chain, it seems possible that the initial transforming event, the t(14; 18) chromosomal translocation, occurs in a cell already committed to the expression of a particular VH and VL gene. A panel of antibodies has been assembled which define a set of idiotypes expressed repeatedly by B-cell lymphomas. Nonetheless, VH gene usage in follicular lymphoma tumors appears to reflect the normal B-cell repertoire. Growth of follicular lymphoma appears to be partially under normal regulatory control. The expanding malignant B-cell clone grows in follicles with particular apposition to follicular dendritic cells and heavy infiltration with CD4+ T cells. Interaction with T cells can induce the proliferation of follicular lymphoma cells. This tumor eventually evolves into a diffuse large-cell lymphoma which is highly aggressive and lethal. It is now clear that the malignant progression occurs from a single cell within the expanding follicular lymphoma clone. A panel of monoclonal antibodies to cell surface molecules has been generated that inhibit proliferation of diffuse lymphoma cell lines, and some of the target molecules have been partially characterized. Therapeutic application of anti-idiotype monoclonal antibodies has shown a high degree of tumor responsiveness, but ultimately escape of idiotype-negative variant cells occurs. These variants arise as a result of extensive somatic point mutation in the VH and VL genes of follicular lymphoma. Active immunization can result in an immune response by patients directed against the idiotype expressed on their own B-cell tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Cell Communication; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Gene Rearrangement, B-Lymphocyte, Light Chain; Humans; Immunoglobulin Idiotypes; Lymphoma, Follicular
PubMed: 2049308
DOI: 10.1007/978-1-4899-7305-4_18