A therapeutic vaccine using Salmonella-modified tumor cells combined with interleukin-2 induces enhanced antitumor immunity in B-cell lymphoma

Grille, Sofía; Moreno, Marı́a; Brugnini, Andreina; Lens, Daniela; Chabalgoity, José A.

doi:10.1016/j.leukres.2012.10.003

Cited by 20 publications

(15 citation statements)

References 45 publications

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“…We have recently reported that Salmonella induces a rapid up-regulation of CD80, CD86 and CD40 as well as of MHC-II in A20 lymphoma cells despite its low infectivity. 41 These in vitro results suggest that Salmonella might increase the antigen-presenting function of lymphoma cells in vivo so that they can then present their own antigen on MHC-I and II to T cells and activate an anti-tumour immune response.…”

Section: Discussionmentioning

confidence: 92%

Salmonella enterica serovar Typhimurium immunotherapy for B‐cell lymphoma induces broad anti‐tumour immunity with therapeutic effect

et al. 2014

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SummaryDespite the efficacy of current immune-chemotherapy for treatment of Bcell non-Hodgkin lymphoma, a substantial proportion of patients relapse, highlighting the need for new therapeutic modalities. The use of live microorganisms to develop anti-tumoural therapies has evolved since Coley's toxin and is now receiving renewed attention. Salmonella Typhimurium has been shown to be highly effective as an anti-tumour agent in many solid cancer models, but it has not been used in haematooncology. Here, we report that intra-tumoural administration of LVR01 (attenuated S. Typhimurium strain with safety profile) elicits local and systemic anti-tumour immunity, resulting in extended survival in a lymphoma model. LVR01 induces intra-tumoural recruitment of neutrophils and activated CD8 + T cells, as well as increasing the natural killer cell activation status. Furthermore, a systemic specific anti-tumour response with a clear T helper type 1 profile was observed. This approach is an alternative therapeutic strategy for lymphoma patients that could be easily moved into clinical trials.

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Section: Discussionmentioning

confidence: 92%

Salmonella enterica serovar Typhimurium immunotherapy for B‐cell lymphoma induces broad anti‐tumour immunity with therapeutic effect

et al. 2014

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“…These responses are associated to Toll-like receptors recognition of pathogen associated molecular patterns (PAMPs) in the bacteria, such as lipopolysaccharide (LPS), teichoic acid, peptidoglycan, and bacterial CpG DNA [ 41 , 47 ]. Although the LVR01 bacterial strain has been extensively tested as carrier for heterologous antigens for human and veterinary vaccination applications [ 48 – 50 ], its use as anticancer agent is relatively recent [ 42 , 51 ] and therefore is still an open area for investigation. Still, the use of Salmonella for anticancer therapies, either as monotherapy or combined, has received extensive consideration in the last decade, showing different degree of effectivity in a number of animal models of major human cancer types including breast cancer [ 52 – 58 ].…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant administration of Semliki Forest virus expressing interleukin-12 combined with attenuated Salmonella eradicates breast cancer metastasis and achieves long-term survival in immunocompetent mice

et al. 2015

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BackgroundMetastatic breast cancer is a major cause of death among women worldwide; therefore efficient therapeutic strategies are extremely needed. In this work we have developed a gene therapy- and bacteria-based combined neoadjuvant approach and evaluated its antitumor effect in a clinically relevant animal model of metastatic breast cancer.Methods2×108 particles of a Semliki Forest virus vector expressing interleukin-12 (SFV-IL-12) and/or 2×107 units of an aroC− Samonella Typhimurium strain (LVR01) were injected into 4T1 tumor nodules orthotopically implanted in mice. Tumors were surgically resected and long-term survival was determined. IL-12 and interferon-γ were quantified by Enzyme-Linked ImmunoSorbent Assay, bacteria was visualized by inmunohistochemistry and the number of lung metastasis was calculated with a clonogenic assay.ResultsSFV-IL-12 and LVR01 timely inoculated and followed by surgical resection of tumors succeeded in complete inhibition of lethal lung metastasis and long-term survival in 90 % of treated mice. The combined therapy was markedly synergistic compared to each treatment alone, since SFV-IL-12 monotherapy showed a potent antiangiogenic effect, being able to inhibit tumor growth and extend survival, but could not prevent establishment of distant metastasis and death of tumor-excised animals. On the other hand, LVR01 alone also showed a significant, although limited, antitumor potential, despite its ability to invade breast cancer cells and induce granulocyte recruitment. The efficacy of the combined therapy depended on the order in which both factors were administered; inasmuch the therapeutic effect was only observed when SFV-IL-12 was administered previous to LVR01, whereas administration of LVR01 before SFV-IL-12 had negligible antitumor activity. Moreover, pre-treatment with LVR01 seemed to suppress SFV-IL-12 antiangiogenic effects associated to lower IL-12 expression in this group. Re-challenged mice were unable to reject a second 4T1 tumor; however 100 % of them could be totally cured by applying the same neoadjuvant combined regimen. To our knowledge, these are the most encouraging results obtained to date in a post-operatory setting using the highly aggressive 4T1 animal model.ConclusionsSFV-IL-12-based gene therapy combined with Salmonella LVR01 neoadjuvant administration has a synergic antitumor effect and may be a promising therapeutic option to prevent and/or eradicate pre-operatory metastasis in locally advanced breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1618-x) contains supplementary material, which is available to authorized users.

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“…Therapeutic vaccination holds enormous potential as a complementary treatment for NHL, and IL-2 has a wide range of immunologic effects and is able to induce regression of metastatic human tumors [107]. In a preclinical study, a therapeutic vaccine using tumor cells activated by Salmonella infection and IL-2 has been shown to induce antitumor immunity in BCL.…”

Section: Additional Novel Strategiesmentioning

confidence: 99%

Novel Therapies for Aggressive B-Cell Lymphoma

Foon¹,

Takeshita²,

Zinzani

2012

Advances in Hematology

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Aggressive B-cell lymphoma (BCL) comprises a heterogeneous group of malignancies, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and mantle cell lymphoma (MCL). DLBCL, with its 3 subtypes, is the most common type of lymphoma. Advances in chemoimmunotherapy have substantially improved disease control. However, depending on the subtype, patients with DLBCL still exhibit substantially different survival rates. In MCL, a mature B-cell lymphoma, the addition of rituximab to conventional chemotherapy regimens has increased response rates, but not survival. Burkitt lymphoma, the most aggressive BCL, is characterized by a high proliferative index and requires more intensive chemotherapy regimens than DLBCL. Hence, there is a need for more effective therapies for all three diseases. Increased understanding of the molecular features of aggressive BCL has led to the development of a range of novel therapies, many of which target the tumor in a tailored manner and are summarized in this paper.

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A therapeutic vaccine using Salmonella-modified tumor cells combined with interleukin-2 induces enhanced antitumor immunity in B-cell lymphoma

Cited by 20 publications

References 45 publications

Salmonella enterica serovar Typhimurium immunotherapy for B‐cell lymphoma induces broad anti‐tumour immunity with therapeutic effect

Salmonella enterica serovar Typhimurium immunotherapy for B‐cell lymphoma induces broad anti‐tumour immunity with therapeutic effect

Neoadjuvant administration of Semliki Forest virus expressing interleukin-12 combined with attenuated Salmonella eradicates breast cancer metastasis and achieves long-term survival in immunocompetent mice

Novel Therapies for Aggressive B-Cell Lymphoma

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