Antibody-CD20-interferon-alpha fusion protein has superior in vivo activity against human B cell lymphomas compared to Rituximab, and enhanced complement-dependent cytotoxicity in vitro

Yamada, Reiko; Steward, Kristopher K.; Ngarmchamnanrith, Gataree; Trinh, Ryan; Khare, Sanjay D.; Sachdev, Raj; Grewal, Iqbal S.; Morrison, Sherie L.; Timmerman, John M.

doi:10.1186/2051-1426-1-s1-p263

Cited by 2 publications

(3 citation statements)

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“…Moreover, anti-CD20-hIFNα achieved superior in vivo efficacy compared to rituximab and non-targeted IFNα fusion protein against human lymphoma xenografts in SCID mice, eradicating 50–88% of established tumors. These results support the further development of anti-CD20-hIFNα for the treatment of B cell NHL, with a phase I first-in-human clinical trial scheduled to begin in 2015 [51]. …”

Section: Antibody-cytokine Fusion Proteins In Clinical Developmentsupporting

confidence: 53%

“…Based on the above results, a new anti-CD20-hIFNα incorporating the antigen-binding sequences from rituximab and full-length human IgG1/κ constant regions is being developed for the treatment of B cell lymphomas (IGN002) [51]. In pre-clinical studies, the IFNα bioactivity was attenuated to approximately 10–20% of conventional rIFNα, though when targeting CD20 + lymphoma cells, growth inhibitory activity is significantly enhanced over rIFNα.…”

Section: Antibody-cytokine Fusion Proteins In Clinical Developmentmentioning

confidence: 99%

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Antibody-Cytokine Fusion Proteins for Treatment of Cancer: Engineering Cytokines for Improved Efficacy and Safety

Young

Morrison

Timmerman

2014

Seminars in Oncology

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The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing IL-2, IL-12, IL-21, TNFα, and interferons α, β and γ have been constructed and have shown anti-tumor activity in pre-clinical and early phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results.

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Section: Antibody-cytokine Fusion Proteins In Clinical Developmentsupporting

confidence: 53%

Section: Antibody-cytokine Fusion Proteins In Clinical Developmentmentioning

confidence: 99%

Antibody-Cytokine Fusion Proteins for Treatment of Cancer: Engineering Cytokines for Improved Efficacy and Safety

Young

Morrison

Timmerman

2014

Seminars in Oncology

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“…Furthermore, conjugating IFN-I with antibodies represents another effective strategy for improving the efficacy of IFN-I therapy. For example, heterodimers of anti-CD20 antibodies and IFN-α fusion proteins (IGN002), which incorporate rituximab's antigen-binding sequences and full-length human IgG1/κ constant regions, are in development for the treatment of B cell lymphoma [141]. Yang et al demonstrated the efficacy of antibody-IFN-β fusion proteins against various solid tumors in mice, targeting the epidermal growth factor receptor (EGFR) and Her2/ neu [142].…”

Section: Progress In the Clinical Development Of Ifn-i Drugsmentioning

confidence: 99%

cGAS-STING pathway mediates activation of dendritic cell sensing of immunogenic tumors

Li,

Zhao,

Zheng

et al. 2024

Cell. Mol. Life Sci.

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Type I interferons (IFN-I) play pivotal roles in tumor therapy for three decades, underscoring the critical importance of maintaining the integrity of the IFN-1 signaling pathway in radiotherapy, chemotherapy, targeted therapy, and immunotherapy. However, the specific mechanism by which IFN-I contributes to these therapies, particularly in terms of activating dendritic cells (DCs), remains unclear. Based on recent studies, aberrant DNA in the cytoplasm activates the cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING) signaling pathway, which in turn produces IFN-I, which is essential for antiviral and anticancer immunity. Notably, STING can also enhance anticancer immunity by promoting autophagy, inflammation, and glycolysis in an IFN-I-independent manner. These research advancements contribute to our comprehension of the distinctions between IFN-I drugs and STING agonists in the context of oncology therapy and shed light on the challenges involved in developing STING agonist drugs. Thus, we aimed to summarize the novel mechanisms underlying cGAS-STING-IFN-I signal activation in DC-mediated antigen presentation and its role in the cancer immune cycle in this review.

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Antibody-CD20-interferon-alpha fusion protein has superior in vivo activity against human B cell lymphomas compared to Rituximab, and enhanced complement-dependent cytotoxicity in vitro

Cited by 2 publications

References 0 publications

Antibody-Cytokine Fusion Proteins for Treatment of Cancer: Engineering Cytokines for Improved Efficacy and Safety

Antibody-Cytokine Fusion Proteins for Treatment of Cancer: Engineering Cytokines for Improved Efficacy and Safety

cGAS-STING pathway mediates activation of dendritic cell sensing of immunogenic tumors

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