Human fibronectin extra domain B as a biomarker for targeted therapy in cancer

Lieverse, Ritsaert; Marcus, Damiënne; Wiel, Alexander M.A. van der; Limbergen, Evert J. Van; Theys, Jan; Yaromina, Ala; Lambin, Philippe

doi:10.1002/1878-0261.12705

Cited by 33 publications

(25 citation statements)

References 69 publications

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“…For example, L19-TNF and L19-IL-2 immunocytokines conjugate an antibodyrecognizing FN with cytokines (TNF-α and IL-2, respectively) (Neri, 2019). Preclinical data already suggested the robust anti-cancer potential of L19-based immunocytokines (Lieverse et al, 2020), and phase II and III trials are currently testing the clinical benefit of L19-TNF-a and L19-IL-2 in patients with soft tissue sarcoma (NCT03420014) or melanoma (NCT02938299, NCT03567889).…”

Section: Overcoming Cafs-induced Immunosuppressionmentioning

confidence: 99%

Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy

Linares

Marín-Jiménez

Badia-Ramentol

et al. 2021

Front. Cell Dev. Biol.

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Multiple lines of evidence are indicating that cancer development and malignant progression are not exclusively epithelial cancer cell-autonomous processes but may also depend on crosstalk with the surrounding tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are abundantly represented in the TME and are continuously interacting with cancer cells. CAFs are regulating key mechanisms during progression to metastasis and response to treatment by enhancing cancer cells survival and aggressiveness. The latest advances in CAFs biology are pointing to CAFs-secreted factors as druggable targets and companion tools for cancer diagnosis and prognosis. Especially, extensive research conducted in the recent years has underscored the potential of several cytokines as actionable biomarkers that are currently evaluated in the clinical setting. In this review, we explore the current understanding of CAFs secretome determinants and functions to discuss their clinical implication in oncology.

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Section: Overcoming Cafs-induced Immunosuppressionmentioning

confidence: 99%

Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy

Linares

Marín-Jiménez

Badia-Ramentol

et al. 2021

Front. Cell Dev. Biol.

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“…The advantage of conjugated cytokines has been proven with IL-2 therapy dramatically reducing toxicity, while extending half-life from minutes to hours [ 140 , 141 ]. Several IL-2 conjugations have been tested, such as L19-IL2 and TNF-ɑ-IL2 [ 142 , 143 ]. However, even if immune cells are actively attracted to the tumor site, stimuli are still needed to target tumor cells.…”

Section: Immunotherapeutic Options and Conventional Radiotherapymentioning

confidence: 99%

Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy

Marcus

Lieverse

Klein

et al. 2021

Cancers

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Radiotherapy (RT) has been shown to interfere with inflammatory signals and to enhance tumor immunogenicity via, e.g., immunogenic cell death, thereby potentially augmenting the therapeutic efficacy of immunotherapy. Conventional RT consists predominantly of high energy photon beams. Hypofractionated RT regimens administered, e.g., by stereotactic body radiation therapy (SBRT), are increasingly investigated in combination with cancer immunotherapy within clinical trials. Despite intensive preclinical studies, the optimal dose per fraction and dose schemes for elaboration of RT induced immunogenic potential remain inconclusive. Compared to the scenario of combined immune checkpoint inhibition (ICI) and RT, multimodal therapies utilizing other immunotherapy principles such as adoptive transfer of immune cells, vaccination strategies, targeted immune-cytokines and agonists are underrepresented in both preclinical and clinical settings. Despite the clinical success of ICI and RT combination, e.g., prolonging overall survival in locally advanced lung cancer, curative outcomes are still not achieved for most cancer entities studied. Charged particle RT (PRT) has gained interest as it may enhance tumor immunogenicity compared to conventional RT due to its unique biological and physical properties. However, whether PRT in combination with immune therapy will elicit superior antitumor effects both locally and systemically needs to be further investigated. In this review, the immunological effects of RT in the tumor microenvironment are summarized to understand their implications for immunotherapy combinations. Attention will be given to the various immunotherapeutic interventions that have been co-administered with RT so far. Furthermore, the theoretical basis and first evidences supporting a favorable immunogenicity profile of PRT will be examined.

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“…Nevertheless, coupling IL2 to a tumour specific antibody, like L19, reduces the IL2 concentration in blood and increases the concentration in the tumour [30,31], resulting in only low grade toxicity [32]. L19-IL2 is a fully human immunocytokine consisting of the human cytokine IL2 fused to the single-chain (scFv) human antibody fragment L19 targeting extra-domain B (ED-B) explicitly [33]. ED-B of fibronectin (FN) is a type III-FN domain, which can be inserted in the protein molecule by a mechanism of alternative splicing [34].…”

Section: Rationalementioning

confidence: 99%

Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial

et al. 2020

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Background: About 50% of non-small cell lung cancer (NSCLC) patients have metastatic disease at initial diagnosis, which limits their treatment options and, consequently, the 5-year survival rate (15%). Immune checkpoint inhibitors (ICI), either alone or in combination with chemotherapy, have become standard of care (SOC) for most good performance status patients. However, most patients will not obtain long-term benefit and new treatment strategies are therefore needed. We previously demonstrated clinical safety of the tumour-selective immunocytokine L19-IL2, consisting of the anti-ED-B scFv L19 antibody coupled to IL2, combined with stereotactic ablative radiotherapy (SABR).

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Human fibronectin extra domain B as a biomarker for targeted therapy in cancer

Cited by 33 publications

References 69 publications

Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy

Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy

Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy

Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial

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