The immunocytokine L19-TNF eradicates sarcomas in combination with chemotherapy agents or with immune check-point inhibitors

Corbellari, Riccardo; Nadal, Lisa; Villa, Alessandra; Neri, Dario; Luca, Roberto De

doi:10.1097/cad.0000000000000938

Cited by 16 publications

(7 citation statements)

References 48 publications

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“…Another chemotherapeutic, decarbazine, as a single agent was capable of eradicating tumors in three out of four mice, but while administered with L19-mTNF, the number of complete responses increased to four of four. Very similar synergistic effects were observed for L19-mTNF and anti-PD-1 antibody [ 101 ]. Anti-tumor effects mediated by antibody-based TNF-α delivery could also be increased by a proper combination with other cytokines, e.g., IL-2.…”

Section: Tnf-based Immunocytokinessupporting

confidence: 68%

Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects

et al. 2023

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Anti-tumor properties of several cytokines have already been investigated in multiple experiments and clinical trials. However, those studies evidenced substantial toxicities, even at low cytokine doses, and the lack of tumor specificity. These factors significantly limit clinical applications. Due to their high specificity and affinity, tumor-specific monoclonal antibodies or their antigen-binding fragments are capable of delivering fused cytokines to tumors and, therefore, of decreasing the number and severity of side effects, as well as of enhancing the therapeutic index. The present review surveys the actual antibody–cytokine fusion protein (immunocytokine) formats, their targets, mechanisms of action, and anti-tumor and other biological effects. Special attention is paid to the formats designed to prevent the off-target cytokine–receptor interactions, potentially inducing side effects. Here, we describe preclinical and clinical data and the efficacy of the antibody-mediated cytokine delivery approach, either as a single therapy or in combination with other agents.

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Section: Tnf-based Immunocytokinessupporting

confidence: 68%

Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects

et al. 2023

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“…After an improved response rate of ipilimumab and L19‐TNF was demonstrated in two syngeneic murine tumor models (F9, CT23), [ 61 ] a very recent study in a BALB/c derived immunocompetent murine model of sarcoma (WEHI‐164) revealed that the combination of L19‐TNF and PD‐1 inhibition was significantly more effective than PD‐1 inhibition alone. [ 62 ] These results, if confirmed in clinical trials, will have major implications for the standard care of human cancers, including melanomas.…”

Section: Open Questions and Experimental Approaches To Take Activatiomentioning

confidence: 89%

Activated melanoma vessels: A sticky point for successful immunotherapy

Weishaupt

Goerge

Loser

2020

Experimental Dermatology

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Is metastatic melanoma curable?-This question has recently been asked more extensively than ever by patients and physicians. [1] New treatment targets such as immune checkpoint blockade (ICB) with PD-1 and CTLA-4 antibodies have become a routine treatment. They have promising long-term outcomes [2] and response rates (40%-63%). [1] However, it needs to be considered that a significant number of melanoma patients will still develop primary resistance or will show progress in the course of treatment (acquired resistance). [3] A major cause of treatment resistance to immunotherapy is characteristics of the tumor tissue itself that allow the tumor to escape from immune responses. [4] Therefore, a fundamental need in

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“…EDB-FN being upregulated in tumor area experiencing neoangiogenesis, L19 contributes to concentrate IL2 in the malignant bed. 149 L19IL2/L19TNF will be administered once weekly for up to 4 weeks into all injectable lesions. Of note, this combination showed promising results in a Phase II clinical trial in patients with advanced metastatic melanoma who were not candidates to surgery ( Table 2 ).…”

Section: Cytokinesmentioning

confidence: 99%

Trial watch: intratumoral immunotherapy

et al. 2021

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While chemotherapy and radiotherapy remain the first-line approaches for the management of most unresectable tumors, immunotherapy has emerged in the past two decades as a game-changing treatment, notably with the clinical success of immune checkpoint inhibitors. Immunotherapies aim at (re)activating anticancer immune responses which occur in two main steps: (1) the activation and expansion of tumor-specific T cells following cross-presentation of tumor antigens by specialized myeloid cells (priming phase); and (2) the immunological clearance of malignant cells by these antitumor T lymphocytes (effector phase). Therapeutic vaccines, adjuvants, monoclonal antibodies, cytokines, immunogenic cell death-inducing agents including oncolytic viruses, anthracycline-based chemotherapy and radiotherapy, as well as adoptive cell transfer, all act at different levels of this cascade to (re)instate cancer immunosurveillance. Intratumoral delivery of these immunotherapeutics is being tested in clinical trials to promote superior antitumor immune activity in the context of limited systemic toxicity.

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The immunocytokine L19-TNF eradicates sarcomas in combination with chemotherapy agents or with immune check-point inhibitors

Cited by 16 publications

References 48 publications

Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects

Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects

Activated melanoma vessels: A sticky point for successful immunotherapy

Trial watch: intratumoral immunotherapy

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