The tumor-targeting immunocytokine F16-IL2 in combination with doxorubicin: dose escalation in patients with advanced solid tumors and expansion into patients with metastatic breast cancer

Catania, Chiara; Maur, M; Berardi, Rossana; Rocca, Andrea; Giacomo, Anna Maria Di; Spitaleri, Gianluca; Masini, Cristina; Pierantoni, Chiara; González-Iglesias, Reinerio; Zigon, Giulia; Tasciotti, Annaelisa; Giovannoni, Leonardo; Lovato, Valeria; Elia, Giuliano; Menssen, Hans D.; Neri, Dario; Cascinu, Stefano; Conte, Pierfranco; Braud, Filippo de

doi:10.4161/19336918.2014.983785

Cited by 52 publications

(40 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, 16 of these studies assessed the safety and efficacy of FDA-approved cytokines (i.e., G-CSF, GM-CSF, IFN-a2a, IFN-a2b and IL-2) as off-label immunostimulatory interventions, [98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113] while only one trial tested the clinical profile of a hitherto experimental cytokine (i.e., IL-15). 114 The safety and efficacy of G-CSF have been assessed in 11 breast carcinoma patients, who were treated with subcutaneous G-CSF in combination with 5-fluorouracil (5-FU), epirubicin, cyclophosphamide and paclitaxel (NCT02225652).…”

Section: Update On the Development Of Recombinant Cytokines As Immunomentioning

confidence: 99%

“…in combination with doxorubicinbased chemotherapy have been evaluated first in 10 subjects with advanced solid tumors (to identify a recommended dose) and subsequently in 19 breast carcinoma patients (at the recommended dose); 104 and the clinical profile of recombinant IL-15 given i.v. or s.c. has been assessed in 18 individuals with advanced melanoma or RCC.…”

Section: Update On the Development Of Recombinant Cytokines As Immunomentioning

confidence: 99%

“…114 These latter two studies identified doses of F16-IL2 and IL-15 that are suitable for further investigation. 104,114 In addition, IL-15 was found to markedly alter the homeostasis of various circulating lymphocyte subsets, notably natural killer (NK), gd T and memory CD8 C T cells.…”

Section: Update On the Development Of Recombinant Cytokines As Immunomentioning

confidence: 99%

See 2 more Smart Citations

Trial Watch—Immunostimulation with cytokines in cancer therapy

Vacchelli¹,

Aranda

Bloy³

et al. 2015

OncoImmunology

View full text Add to dashboard Cite

During the past decade, great efforts have been dedicated to the development of clinically relevant interventions that would trigger potent (and hence potentially curative) anticancer immune responses. Indeed, developing neoplasms normally establish local and systemic immunosuppressive networks that inhibit tumor-targeting immune effector cells, be them natural or elicited by (immuno)therapy. One possible approach to boost anticancer immunity consists in the (generally systemic) administration of recombinant immunostimulatory cytokines. In a limited number of oncological indications, immunostimulatory cytokines mediate clinical activity as standalone immunotherapeutic interventions. Most often, however, immunostimulatory cytokines are employed as immunological adjuvants, i.e., to unleash the immunogenic potential of other immunotherapeutic agents, like tumor-targeting vaccines and checkpoint blockers. Here, we discuss recent preclinical and clinical advances in the use of some cytokines as immunostimulatory agents in oncological indications.

show abstract

Section: Update On the Development Of Recombinant Cytokines As Immunomentioning

confidence: 99%

Section: Update On the Development Of Recombinant Cytokines As Immunomentioning

confidence: 99%

See 1 more Smart Citation

Trial Watch—Immunostimulation with cytokines in cancer therapy

Vacchelli¹,

Aranda

Bloy³

et al. 2015

OncoImmunology

View full text Add to dashboard Cite

show abstract

“…Indeed, amongst 11 highly immunogenic peptides that have been delivered within an immunization cocktail to glioblastoma patients (clinical trial phase I), one represented tenascin-C (Dutoit et al, 2012;Rampling et al, 2016). Moreover, aptamers and antibodies that specifically bind to tenascin-C were applied to deliver drugs or immune stimulatory chemokines, such as IL2, into the tumor microenvironment of patients with different cancers (Catania et al, 2015;Gutbrodt et al, 2013 ; reviewed in Spenle et al, 2015b). Furthermore, tenascin-C gene expression negatively influences the cytotoxicity of doxorubicin in breast cancer and melanoma spheroids, as well as pancreatic cancer cells (Fukunaga-Kalabis et al, 2010;Oskarsson et al, 2011), suggesting that tenascin-C is a good target for adjuvant chemotherapy.…”

Section: Tenascin-c In Tissuesmentioning

confidence: 99%

Tenascin-C at a glance

Midwood

Chiquet

Tucker

et al. 2016

Journal of Cell Science

326

357

View full text Add to dashboard Cite

Tenascin-C (TNC) is a hexameric, multimodular extracellular matrix protein with several molecular forms that are created through alternative splicing and protein modifications. It is highly conserved amongst vertebrates, and molecular phylogeny indicates that it evolved before fibronectin. Tenascin-C has many extracellular binding partners, including matrix components, soluble factors and pathogens; it also influences cell phenotype directly through interactions with cell surface receptors. Tenascin-C protein synthesis is tightly regulated, with widespread protein distribution in embryonic tissues, but restricted distribution of tenascin-C in adult tissues. Tenascin-C is also expressed de novo during wound healing or in pathological conditions, including chronic inflammation and cancer. First described as a modulator of cell adhesion, tenascin-C also directs a plethora of cell signaling and gene expression programs by shaping mechanical and biochemical cues within the cellular microenvironment. Exploitment of the pathological expression and function of tenascin-C is emerging as a promising strategy to develop new diagnostic, therapeutic and bioengineering tools. In this Cell Science at a Glance article and the accompanying poster we provide a succinct and comprehensive overview of the structural and functional features of tenascin-C and its potential roles in developing embryos and under pathological conditions.

show abstract

“…This drug has generated responses, including a CR in post- allogeneic hematopoietic stem cell transplant AML patients[287]. Its efficacy in combination with doxorubicin is also being investigated in solid tumors[288]. …”

Section: Antibodies As Targeting Vehiclesmentioning

confidence: 99%

Mechanisms of action of therapeutic antibodies for cancer

Redman

Hill

Aldeghaither

et al. 2015

Molecular Immunology

142

View full text Add to dashboard Cite

The therapeutic utility of antibodies and their derivatives is achieved by various means. The FDA has approved several targeted antibodies that disrupt signaling of various growth factor receptors for the treatment of a number of cancers. Rituximab, and other anti-CD20 monoclonal antibodies are active in B cell malignancies. As more experience has been gained with anti-CD20 monoclonal antibodies, the multifactorial nature of their anti-tumor mechanisms has emerged. Other targeted antibodies function to dampen inhibitory checkpoints. These checkpoint inhibitors have recently achieved dramatic results in several cancers, including melanoma. These and related antibodies continue to be investigated in the clinical and pre-clinical settings. Novel antibody structures that target two or more antigens have also made their way into clinical use. Tumor targeted antibodies can also be conjugated to chemo- or radiotherapeutic agents, or catalytic toxins, as a means to deliver toxic payloads to cancer cells. Here we provide a review of these mechanisms and a discussion of their relevance to current and future clinical applications.

show abstract

The tumor-targeting immunocytokine F16-IL2 in combination with doxorubicin: dose escalation in patients with advanced solid tumors and expansion into patients with metastatic breast cancer

Cited by 52 publications

References 22 publications

Trial Watch—Immunostimulation with cytokines in cancer therapy

Trial Watch—Immunostimulation with cytokines in cancer therapy

Tenascin-C at a glance

Mechanisms of action of therapeutic antibodies for cancer

Contact Info

Product

Resources

About