Breaking Tolerance in a Mouse Model of Multiple Myeloma by Chemoimmunotherapy

Sharabi, Amir; Ghera, Nechama Haran

doi:10.1016/s0065-230x(10)07001-6

Cited by 24 publications

(15 citation statements)

References 133 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adoptive transfer of Tregs from 5T2MM-bearing immunocompetent C57/KalwRij mice into syngeneic mice led, in contrast to Treg infusions in the previously described xenogeneic transplantation model [85], to increased progression of MM disease in recipient mice [87]. These results suggest that cultured Tregs in xenogeneic murine transplantation models are susceptible to bone marrow stroma-mediated neutralization of their suppressive activity, while Tregs isolated from myelomabearing syngeneic mice may be less susceptible to this neutralization [117] or present a more suppressive phenotype.…”

Section: Adoptive T-cell Transfermentioning

confidence: 69%

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

Binsfeld

Fostier

Muller

et al. 2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

View full text Add to dashboard Cite

The majority of multiple myeloma patients relapse with the current treatment strategies, raising the need for alternative therapeutic approaches. Cellular immunotherapy is a rapidly evolving field and currently being translated into clinical trials with encouraging results in several cancer types, including multiple myeloma. Murine multiple myeloma models are of critical importance for the development and refinement of cellular immunotherapy. In this review, we summarize the immune cell changes that occur in multiple myeloma patients and we discuss the cell-based immunotherapies that have been tested in multiple myeloma, with a focus on murine models.

show abstract

Section: Adoptive T-cell Transfermentioning

confidence: 69%

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

Binsfeld

Fostier

Muller

et al. 2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

View full text Add to dashboard Cite

show abstract

“…There is limited information about the kinetics and function of Tregs following CYC induced transient Treg depletion (including recovery to pretreatment levels) in patients with cancer. The duration of the blocked renewal of Tregs following CYC treatment might be important when considering repeated administrations of low-dose CYC at longer intervals using the window opportunity [4, 59]. …”

Section: Cyc In Cancer Therapymentioning

confidence: 99%

“…However, a higher MM incidence (80–85%) was observed in those treated with the high-dose in comparison with the low-dose CYC (40–50%) [4]. Further, mice treated not with low-dose but with high-dose CYC still had residual 5T2MM cells, because adoptive transfer of BM cells from grossly appearing mice 170 days after initiation of treatment into young syngeneic recipients resulted in the development of disease in the BM of the latter 3-4 months afterwards [59]. …”

Section: Cyc In Cancer Therapymentioning

confidence: 99%

“…These shorter time intervals limited the “window of opportunity” by preventing recruitment of effector T cells, NKT, or DCs required for the reduction of MM incidence. Continuous low-dose CYC treatments at 45-day intervals were shown to be most effective in reducing and/or preventing MM development [4, 59]. Moreover, even when the initial injection of a high-dose CYC was chosen, further repeated injections of low-dose CYC at 45-day intervals prevented the disease [59].…”

Section: Cyc In Cancer Therapymentioning

confidence: 99%

See 1 more Smart Citation

Immune Recovery after Cyclophosphamide Treatment in Multiple Myeloma: Implication for Maintenance Immunotherapy

Sharabi

Haran-Ghera

2011

Bone Marrow Research

Self Cite

View full text Add to dashboard Cite

Multiple myeloma (MM) is a progressive B-lineage neoplasia characterized by clonal proliferation of malignant plasma cells. Increased numbers of regulatory T cells (Tregs) were determined in mouse models and in patients with MM, which correlated with disease burden. Thus, it became rational to target Tregs for treating MM. The effects of common chemotherapeutic drugs on Tregs are reviewed with a focus on cyclophosphamide (CYC). Studies indicated that selective depletion of Tregs may be accomplished following the administration of a low-dose CYC. We report that continuous nonfrequent administrations of CYC at low doses block the renewal of Tregs in MM-affected mice and enable the restoration of an efficient immune response against the tumor cells, thereby leading to prolonged survival and prevention of disease recurrence. Hence, distinctive time-schedule injections of low-dose CYC are beneficial for breaking immune tolerance against MM tumor cells.

show abstract

“…A promising alternative strategy is the development of specific immunotherapies selectively targeting myeloma cells [10][11][12][13] . However, a major problem in this area is the immune tolerance to tumor cells and tumor-associated antigens [14,15] . To overcome this problem, this study examined the potential of improving the antigenicity of myeloma through metabolic engineering of its cell surface carbohydrate antigens.…”

Section: Introductionmentioning

confidence: 99%

N-Propionyl polysialic acid precursor enhances the susceptibility of multiple myeloma to antitumor effect of anti-NprPSA monoclonal antibody

Xiong

Liang

et al. 2012

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: To study the antitumor effect of anti-NprPSA monoclonal antibody (mAb) in combination with ManNPr, a precursor of N-propionyl PSA, in multiple myeloma (MM), and to explore the mechanisms of the action. Methods: Human multiple myeloma cell line RPMI-8226 was tested. The cells were pre-treated with ManNPr (1, 2, and 4 mg/mL), and then incubated with anti-NprPSA mAb (1 mg/mL). Cell apoptosis in vitro was detected using MTT assay and flow cytometry. BALB/c nude mice were inoculated sc with RPC5.4 cells. On 5 d after the injection, the mice were administered sc with anti-NprPSA mAb (200 μg/d) and ManNPr (5 mg/d) for 8 d. The tumor size and body weight were monitored twice per week. TUNEL assay was used for detecting apoptosis in vivo. The apoptotic pathway involved was examined using Western blot analysis and caspase inhibitor. Results: Treatment of RPMI-8226 cells with anti-NprPSA mAb alone failed to inhibit cell growth in vitro. In RPMI-8226 cells pretreated with ManNPr, however, the mAb significantly inhibited the cell proliferation, decreased the viability, and induced apoptosis, which was associated with cleavage of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase. In the mouse xenograft model, treatment with the mAb in combination with ManNPr significantly inhibited the tumor growth, and induced significant apoptosis as compared to treatment with the mAb alone. Moreover, apoptosis induced by the mAb in vivo resulted from the activation of the caspases and poly(ADP-ribose) polymerase. Conclusion: The anti-NprPSA mAb in combination with ManNPr is an effective treatment for in vitro and in vivo induction of apoptosis in multiple myeloma.

show abstract

Breaking Tolerance in a Mouse Model of Multiple Myeloma by Chemoimmunotherapy

Cited by 24 publications

References 133 publications

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

Immune Recovery after Cyclophosphamide Treatment in Multiple Myeloma: Implication for Maintenance Immunotherapy

N-Propionyl polysialic acid precursor enhances the susceptibility of multiple myeloma to antitumor effect of anti-NprPSA monoclonal antibody

Contact Info

Product

Resources

About