Idiotype protein vaccination in combination with adjuvant cytokines in patients with multiple myeloma - evaluation of T-cell responses by different read-out systems

Abdalla, Amir Osman; Hansson, Lotta; Eriksson, Ingrid; Näsman-Glaser, Barbro; Rossmann, Eva; Rabbani, Hodjattallah; Mellstedt, Håkan; Österborg, Anders

doi:10.3324/haematol.10095

Cited by 22 publications

(14 citation statements)

References 15 publications

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“…GM-CSF/IL-12 has been used in multiple myeloma patients, where the combined actions of both cytokines led to a reduction in circulating tumor B cells [75][76][77]. Idiotype-specific immune responses were observed in the majority (75-85%) of patients treated with both GM-CSF and IL-12, as compared to 20-30% of the patients treated with IL-12 alone, and were inversely correlated with the frequency of CD4 + /CD25 + T regulatory cells.…”

Section: Granulocyte-macrophage Colony-stimulating Factor (Gm-csf)/il-12mentioning

confidence: 99%

Immunotherapy of cancer by IL-12-based cytokine combinations

Weiss

Subleski

Wigginton

et al. 2007

Expert Opinion on Biological Therapy

204

121

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Cancer is a multi-faceted disease comprising complex interactions between neoplastic and normal cells. Over the past decade, there has been considerable progress in defining the molecular, cellular and environmental contributions to the pathophysiology of tumor development. Despite these advances, the conventional treatment of patients still generally involves surgery, radiotherapy and/ or chemotherapy and the clinical outcome for many of these efforts remains unsatisfactory. Recent studies have highlighted the feasibility of using immunotherapeutic approaches that seek to enhance host immune responses to developing tumors. These strategies include immunomodulatory cytokines, with tumor necrosis factor (TNF) alpha, type I or type II Interferons (IFNs), Interleukins (IL)-2, IL-12, IL-15 and IL-18 being among the most potent inducers of anti-tumor activity in a variety of pre-clinical studies. More recently, some exciting new cytokines have been characterized, such as IL-21, IL-23, IL-27, and their immunomodulatory and anti-tumor effects in vitro and in vivo suggest that they may have considerable promise for future immunotherapy protocols. The promise of cytokine therapy does indeed derive from the identification of these novel cytokines, but even more fundamentally, the field is greatly benefiting from the ever-expanding amount of preclinical data that convincingly demonstrate synergistic and/or novel biological effects that may be achieved through the use of several combinations of cytokines with complementary immunestimulating capabilities. One cytokine in particular, IL-12, holds considerable promise by virtue of the fact that it plays a central role in regulating both innate and adaptive immune responses, can by itself induce potent anti-cancer effects, and synergizes with several other cytokines for increased immunoregulatory and anti-tumor activities. This review will discuss the anti-tumor activity of IL-12, with a special emphasis on its ability to synergize with other cytokines for enhancement of immune effector cell populations and regulation of host-tumor cell interactions and the overall tumor microenvironment.

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Section: Granulocyte-macrophage Colony-stimulating Factor (Gm-csf)/il-12mentioning

confidence: 99%

Immunotherapy of cancer by IL-12-based cytokine combinations

Weiss

Subleski

Wigginton

et al. 2007

Expert Opinion on Biological Therapy

204

121

View full text Add to dashboard Cite

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“…In other studies, Id-KLH vaccines failed to elicit an anti-Id immune response in more than half of the patients [4,12,21]. In Id vaccine trials with myeloma patients using Id-pulsed dendritic cells amongst others, altogether about 55% of patients mounted an Id-specific response and about 12% displayed a clinical response [23,24]. Clinical response was difficult to evaluate in the majority of studies, because vaccines were mostly conducted in a state of minimal residual disease based on the presumption derived from animal studies that vaccinations are more successful in a state of low tumor burden, entailing that most patients had previously received cytoreductive and immunosuppressive therapy [16].…”

Section: Discussionmentioning

confidence: 99%

Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma

et al. 2014

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BackgroundMultiple myeloma is characterized by clonal expansion of B cells producing monoclonal immunoglobulins or fragments thereof, which can be detected in the serum and/or urine and are ideal target antigens for patient-specific immunotherapies.MethodsUsing phage particles as immunological carriers, we employed a novel chemically linked idiotype vaccine in a clinical phase I/II trial including 15 patients with advanced multiple myeloma. Vaccines composed of purified paraproteins linked to phage were manufactured successfully for each patient. Patients received six intradermal immunizations with phage idiotype vaccines in three different dose groups.ResultsPhage idiotype was well tolerated by all study participants. A subset of patients (80% in the middle dose group) displayed a clinical response indicated by decrease or stabilization of paraprotein levels. Patients exhibiting a clinical response to phage vaccines also raised idiotype-specific immunoglobulins. Induction of a cellular immune response was demonstrated by a cytotoxicity assay and delayed type hypersensitivity tests.ConclusionWe present a simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible patient-specific therapy for patients with advanced multiple myeloma and produced promising anti-tumor activity in a subset of patients.

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“…However, the use of GM-CSF in Id-vaccination is controversial, as on the one hand GM-CSF might be important for inducing a T cell response to Id vaccination, which is supported by the fact that GM-CSF in combination with IL-12 leads to a stronger induction of an Id-specific T cell response than IL-12 alone in myeloma patients [31,32]. On the other hand, GM-CSF was shown to induce growth-stimulating effects on human myeloma cells in vitro [33] and extramedullary progression of multiple myeloma [34].…”

Section: Discussionmentioning

confidence: 99%

Chemically linked phage idiotype vaccination in the murine B cell lymphoma 1 model

et al. 2013

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BackgroundB cell malignancies are characterized by clonal expansion of B cells expressing tumor-specific idiotypes on their surface. These idiotypes are ideal target antigens for an individualized immunotherapy. However, previous idiotype vaccines mostly lacked efficiency due to a low immunogenicity of the idiotype. The objective of the present study was the determination of the feasibility, safety and immunogenicity of a novel chemically linked phage idiotype vaccine.MethodsIn the murine B cell lymphoma 1 model, tumor idiotypes were chemically linked to phage particles used as immunological carriers. For comparison, the idiotype was genetically expressed on the major phage coat protein g8 or linked to keyhole limpet hemocynanin. After intradermal immunizations with idiotype vaccines, tolerability and humoral immune responses were assessed.ResultsFeasibility and tolerability of the chemically linked phage idiotype vaccine was demonstrated. Vaccination with B cell lymphoma 1 idiotype expressing phage resulted in a significant survival benefit in the murine B cell lymphoma 1 protection model (60.2 ± 23.8 days vs. 41.8 ± 1.6 days and 39.8 ± 3.8 days after vaccination with wild type phage or phosphate buffered saline, respectively). Superior immunogenicity of the chemically linked phage idiotype vaccine compared to the genetically engineered phage idiotype and keyhole limpet hemocynanin-coupled idiotype vaccine was demonstrated by significantly higher B cell lymphoma 1 idiotype-specific IgG levels after vaccination with chemically linked phage idiotype.ConclusionWe present a novel, simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible therapy and may produce a superior immune response compared to previously employed idiotype vaccination strategies.

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Idiotype protein vaccination in combination with adjuvant cytokines in patients with multiple myeloma - evaluation of T-cell responses by different read-out systems

Cited by 22 publications

References 15 publications

Immunotherapy of cancer by IL-12-based cytokine combinations

Immunotherapy of cancer by IL-12-based cytokine combinations

Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma

Chemically linked phage idiotype vaccination in the murine B cell lymphoma 1 model

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