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Jetzt testen 1. Med Innere Medizin Kombi-Abonnement. Jetzt testen 2. Br J Cancer — CrossRef. Kidney Int — CrossRef.

Clin Cancer Res — CrossRef. Case Rep Oncol Med. Am J Kidney Dis. Ann Oncol iv—iv CrossRef. Kidney Int CrossRef.

Intern Med — CrossRef. Nephrol Dial Transplant — CrossRef. Ann Oncol — CrossRef. Curr Probl Cancer — CrossRef.

Clin Med Insights Case Rep. Cancer Treat Rev —60 CrossRef. Nat Rev Nephrol — CrossRef. Cancer Treat Res — Clin Case Rep — CrossRef.

Cancer Immunol Res — CrossRef. OncoImmunology 7:e CrossRef. Autoren: S. Anker L. Hannemann K. Benesova C. Eckert K.

Jordan C. Schulte Dr. Publikationsdatum Leitthema Palliative Versorgung von krebskranken Nierenpatienten. Für Sie gelesen Albuminurie ohne Nierenfunktionsverlust.

Update Nephrologie Kardiovaskuläre Komplikationen. Med Mein e. The immunocytokine showed an increased inhibition of tumor growth compared to untargeted TNF treatment in mouse models of fibrosarcoma and colorectal cancer [ 10 ].

Interestingly, most of the subcutaneous tumor mass became necrotic after a single intravenous administration of LTNF [ 26 ].

A synergistic effect was observed when LTNF was combined to mephalan [ 26 ]. Combination studies with LIL2 and LIL12 also showed strong additive antitumoral effects on models of murine teratocarcinoma and neuroblastoma [ , ].

Phase III clinical studies are currently testing the combination of the fully-human LTNF product Fibromun , administered intravenously, with doxorubicin in soft-tissue sarcoma patients.

Immunohistochemical analyses of tumor sections showed accumulation of the LTNF at sites of tumor neo-angiogenesis [ ].

A potent anticancer activity of LTNF was also observed upon intralesional administration in combination with LIL2 in patients with inoperable metastatic melanoma [ ].

Other antibodies can also be considered for TNF delivery applications. The F8 antibody, specific to EDA fibronectin, was fused to murine TNF in scFv format and used as single agent or in combination with doxorubicin for the treatment of syngeneic murine tumor models of sarcoma.

The combination regimen of doxorubicin and F8-TNF led to complete eradication of the tumor and long-lasting immunoprotection [ 55 , 71 ].

Generally, such retroviral sequences have been found also in the genome of vertebrate species and their expression has been associated with autoimmune diseases, chronic infections or cancer [ , ].

In theory, a TNF-based immunocytokine could cause upregulation of a subset of cytotoxic T cells specific for a retroviral antigen found in human tumors, which would contribute to the antitumoral effect in patients.

Preclinical studies on a murine melanoma model revealed that the therapeutic activity of an anti-melanoma immunoglobulin IgG2a TA99 was significantly potentiated when combined with the TNF antibody fusion protein TAmTNF.

The increased density of leukocytes in the subcutaneous melanoma masses of mice treated with the combination treatment favored tumor cell killing through ADCC [ ].

Interleukin IL12 is a heterodimeric cytokine, composed by the p40 and p35 moieties linked by a disulfide bond, which provides a crucial connection between the innate and the adaptive immune system [ ].

The product, developed by Merck is currently being tested in Phase I trials as monotherapy or in combination with avelumab anti-PD-L1 antibody [ , ].

BC1-IL12 recognizes an epitope on domain 7 of fibronectin, which is cryptic i. The fusion protein consists of the full IgG1 linked to the IL12 heterodimer at the C-terminus of the heavy chain.

Efficient in vivo localization [ ] and anti-tumor activity have been confirmed in various mouse models of cancer [ 54 ].

When tested on patients with malignant melanoma in a Phase I clinical study, BC1-IL12 led to disease stabilization in 6 out of 11 patients for at least 4 months [ ].

The heterodimeric nature of the IL12 and of the resulting fusion proteins allows the implementation of various types of immunocytokine formats Figure 2 [ 7 , 17 , 29 , 32 ], which however may represent a challenge for successful protein production.

In the formats studied so far, the p35 and p40 subunits were typically connected by a peptide linker. Halin et al. The fusion protein was compared to untargeted IL12 in therapy studies on a mouse model of lung metastasis and two subcutaneous tumor models.

ILL19 displayed much stronger inhibition of tumor progression compared to the untargeted control and increased leukocyte infiltrate into the tumor masses.

Other formats were investigated with the aim to increase tumor:organ ratios. ILSIP L19 featuring a C-terminal CH4 domain of human IgE in order to favor the homodimerization of the fusion protein, accumulated mainly in the liver and exhibited modest tumor uptake compared to a heterotrimeric fusion protein having p40 linked to scFv L19 forming a non covalent dimer with scFv L19 -p This fusion protein showed an efficient tumor uptake in F9 teratocarcinoma mouse tumor models, with tumor:organ ratios of —, 24 hours after intravenous administration [ 29 ].

The F8 antibody, specific to EDA fibronectin, was fused to murine IL12 in different formats [ 17 , 32 ] and tested both in vitro and in vivo.

ILF8-F8 efficiently inhibited tumor growth in three different immunocompetent syngeneic models of cancer.

The effect was strongly potentiated by combination with paclitaxel [ 17 ]. Our group systematically explored the targeted delivery of cytokines from the TNF superfamily e.

A lower accumulation compared to TNF fusions was observed in the tumor mass of various murine cancer models [ ].

Recent work of the group of Roland Kontermann showed that better tumor homing properties might be achieved if the TNF superfamily cytokines are expressed as single chain polypeptides [ 30 , ] Figure 2.

IL15 is a pro-inflammatory cytokine that features certain functional redundancies with IL2, as both cytokines signal through the beta and gamma subunits of the same receptor.

Targeted delivery of GM-CSF to the tumors showed enhanced antitumor activity [ 50 , 74 ], as well as increased antigen processing and presentation [ , ].

Finally, it is conceivable to fuse two cytokines the same antibody, in order to exploit a synergistic benefit by the simultaneous presence of the two payloads at the site of disease.

The in vivo activity of cytokines and of their derivatives depends on the immunological environment and on the concentration of the cytokine at the site of disease.

Certain payloads may display a pro- or anti-inflammatory action depending on the immunological context [ — ]. More examples, reviewed by Cavaillon JM e.

Even though research has mainly focused on immunocytokines directed against oncological targets, potential applications in chronic inflammatory diseases have recently gained momentum.

One product based on IL10 F8-IL10 is currently being investigated in Phase II clinical trials in patients with rheumatoid arthritis or ulterative colitis, while other products have shown promising signs of efficacy in animal models [ 14 , ].

IL10 is a homodimeric, pleiotropic cytokine, with a potential to display an immunosuppressive activity at sites of inflammation, for example by reducing antigen presentation and the release of pro-inflammatory mediators [ ].

Recombinant IL10 has been tested in various mouse models of inflammation showing encouraging results [ 60 , 61 ].

Initial clinical studies have shown no significant differences in remission rates or disease improvements were reported [ , ].

However, a pegylated version of murine IL10 induced rejection of solid and metastasizing tumors in mice by induction of cytotoxic T cells [ , ].

In clinical trials the recombinant pegylated interleukin PEG-rIL increased the density of activated intratumoral cytotoxic T cells in patients [ ].

The antibody-cytokine fusion LIL10 selectively localized to sites of inflammation in mouse models [ 13 ].

In the mouse model of collagen induced arthritis CIA , LIL10 treatment induced a significant inhibition of disease progression, compared to control mice treated with saline or with an IL10 fusion based on an antibody of irrelevant specificity [ 13 ].

Similarly, fusion of IL10 with the F8 antibody specific to EDA fibronectin [ ] showed disease targeting and an encouraging activity in the murine CIA model [ , ], both, alone or in combination with methotrexate or a TNF inhibitor.

The product was also active in a mouse model of endometriosis [ 63 ]. IL4 production is limited to a small subset of hematopoietic cells and the effects are mediated by a high affinity heterodimeric IL4 receptor.

Recombinant IL4 reduced disease progression in preclinical models of rheumatoid arthritis [ ], but failed to reproduce these results in human clinical studies[ ].

By contrast, recombinant IL4 switched the immune environment to a T H 2 pattern and markedly improved conditions in patients with moderate-to-severe T H 1 mediated psoriasis [ ].

The antibody-based delivery of IL4 at the site of chronic inflammation is thought to generate a more specific and focused immunomodulatory action.

The F8-IL4 fusion protein Tetravil , based on the EDA targeting antibody in diabody format, selectively accumulated in the proximity of newly formed blood vessels in arthritic paws and toes of mice with CIA.

The combination therapy rapidly resolved the inflammatory process in the paws, by recruiting TH2 cells and Tregs and by normalizing the concentration of pro-inflammatory cytokines [ 14 , , ].

In addition, treatment with F8-IL4 significantly inhibited endometriotic lesion growth in a mouse model, compared to untargeted IL4, which did not exhibit in vivo activity [ 62 ].

The therapeutic effect of F8-IL4 was also observed in imiquimod-induced and contact-hypersensitivity-induced mouse models of skin inflammation [ ].

Motivated by these encouraging data, F8-IL4 is currently being considered for clinical testing for the treatment of rheumatoid arthritis and endometriosis [ ].

A large variety of immunocytokines has been generated for multiple therapeutic applications in the past two decades. Even though only a few of those proceeded to clinical stage so far, the potential of antibody-cytokine fusion proteins is enormous.

Immunocytokines may synergize with several combination partners, such as cytotoxic drugs [ 26 , 44 , 53 , 71 , — , ], radiation [ 44 , 96 , , ], monoclonal antibodies [ 44 , 99 , ], SMDCs [ ], antibody drug conjugates [ , ], cancer vaccines [ , ], immunecheckpoint inhibitors [ 39 , 56 , 57 , , , ], bispecific antibodies [ — ], and other immunocytokines[ 17 , 57 , , , — , , ].

Over the next few years, the outcome of on-going clinical trials will shed light on the therapeutic benefit that can be achieved, while new protein engineering approaches will contribute to the development of second-generation products.

The authors would like to thank Jonathan Kiefer and Dr. Samuele Cazzamalli for proofreading the manuscript.

National Center for Biotechnology Information , U. N Biotechnol. Author manuscript; available in PMC Mar Author information Copyright and License information Disclaimer.

Copyright notice. The publisher's final edited version of this article is available at N Biotechnol. See other articles in PMC that cite the published article.

Abstract Antibody-cytokine fusion proteins represent a novel class of biopharmaceuticals, with the potential to increase the therapeutic index of cytokine payloads and to promote leukocyte infiltration at the site of disease.

From cytokines to immunocytokines Cytokines are small immunoregulatory proteins, which are secreted by leukocytes and, in some cases, by endothelial cells, fibroblasts and stromal cells.

Immunocytokine formats Antibodies can be used in full immunoglobulin G IgG format, in order to exploit the stability and long circulatory half-life of these products.

Open in a separate window. Figure 1. Figure 2. Targets for oncological and non-oncological conditions Ideal target antigens for the development of immunocytokine products should be abundantly expressed at the site of disease and absent in healthy tissues.

Cytokine payloads Both for cancer therapy as well as for the treatment of chronic inflammation, several cytokine payloads have been developed and tested in preclinical trials.

Payloads can broadly be grouped into five distinct categories in the mouse: i. Immunocytokines for cancer therapy The targeted delivery of cytokines to the tumor aims at inducing a local pro-inflammatory environment, which may activate and recruit immune cells.

Table 1 List of immunocytokines in clinical trials. IL2-based immunocytokines Interleukin-2 IL2 is one of the best-characterized cytokines for tumor therapy applications, since the corresponding recombinant human protein is a product on the market e.

IL based immunocytokines Interleukin IL12 is a heterodimeric cytokine, composed by the p40 and p35 moieties linked by a disulfide bond, which provides a crucial connection between the innate and the adaptive immune system [ ].

Immunocytokines for the therapy of chronic inflammatory conditions The in vivo activity of cytokines and of their derivatives depends on the immunological environment and on the concentration of the cytokine at the site of disease.

Conclusions A large variety of immunocytokines has been generated for multiple therapeutic applications in the past two decades. Acknowledgements The authors would like to thank Jonathan Kiefer and Dr.

References 1. Murphy KP, et al. Janeway Immunology. New York: Garland Science; Geertsen PF, et al. Safety and efficacy of subcutaneous and continuous intravenous infusion rIL-2 in patients with metastatic renal cell carcinoma.

Br J Cancer. Lejeune F, et al. Rationale for using TNF alpha and chemotherapy in regional therapy of melanoma. J Cell Biochem.

Leonard JP, et al. Effects of single-dose interleukin exposure on interleukinassociated toxicity and interferon-gamma production.

Baldo BA. Side effects of cytokines approved for therapy. Drug Saf. Lode HN, et al. Immunocytokines: a promising approach to cancer immunotherapy.

Pharmacol Ther. Halin C, et al. Enhancement of the antitumor activity of interleukin by targeted delivery to neovasculature.

Nat Biotechnol. Pancook JD, et al. Eradication of established hepatic human neuroblastoma metastases in mice with severe combined immunodeficiency by antibody-targeted interleukin Cancer Immunol Immunother.

Targeted interleukin-2 therapy for spontaneous neuroblastoma metastases to bone marrow. J Natl Cancer Inst. Balza E, et al.

Targeted delivery of tumor necrosis factor-alpha to tumor vessels induces a therapeutic T cell-mediated immune response that protects the host against syngeneic tumors of different histologic origin.

Clin Cancer Res. Carnemolla B, et al. Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix.

Gillies SD, et al. Trachsel E, et al. Antibody-mediated delivery of IL inhibits the progression of established collagen-induced arthritis.

Arthritis Res Ther. Antibody-based delivery of IL4 to the neovasculature cures mice with arthritis.

Yokota T, et al. Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms.

Cancer Res. Borsi L, et al. Selective targeting of tumoral vasculature: comparison of different formats of an antibody L19 to the ED-B domain of fibronectin.

Int J Cancer. Pasche N, et al. The antibody-based delivery of interleukin to the tumor neovasculature eradicates murine models of cancer in combination with paclitaxel.

Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. Strohl WR.

Improving the efficacy of antibody-interleukin 2 fusion proteins by reducing their interaction with Fc receptors. Shinkawa T, et al.

The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity.

J Biol Chem. Theoretical analysis of antibody targeting of tumor spheroids: importance of dosage for penetration, and affinity for retention.

Adams GP, et al. Avidity-mediated enhancement of in vivo tumor targeting by single-chain Fv dimers. Wu AM, et al.

Tumor localization of anti-CEA single-chain Fvs: improved targeting by non-covalent dimers. Selective targeted delivery of TNFalpha to tumor blood vessels.

Ongaro T, et al. A novel anti-cancer Linterleukin fusion protein with an optimized peptide linker efficiently localizes in vivo at the site of tumors.

J Biotechnol. Fellermeier S, et al. Advancing targeted co-stimulation with antibody-fusion proteins by introducing TNF superfamily members in a single-chain format.

An engineered antibody-interleukin fusion protein with enhanced tumor vascular targeting properties.

Krippner-Heidenreich A, et al. J Immunol. Schneider B, et al. Potent antitumoral activity of TRAIL through generation of tumor-targeted single-chain fusion proteins.

Cell Death Dis. Sommavilla R, et al. Expression, engineering and characterization of the tumor-targeting heterodimeric immunocytokine F8-IL Protein Eng Des Sel.

Neri D, Bicknell R. Tumour vascular targeting. Nat Rev Cancer. Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy.

Nat Rev Drug Discov. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Rybak JN, et al. The extra-domain A of fibronectin is a vascular marker of solid tumors and metastases.

Zardi L, et al. Transformed human cells produce a new fibronectin isoform by preferential alternative splicing of a previously unobserved exon.

EMBO J. Extracellular pH controls pre-mRNA alternative splicing of tenascin-C in normal, but not in malignantly transformed, cells.

Nicolini V, et al. A novel antibodyBBL fusion protein for targeted costimulation in cancer immunotherapy.

J Immunother. Mach JP, et al. Use of radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintigraphy.

Immunol Today. Violet JA, et al. Fractionated I anti-CEA radioimmunotherapy: effects on xenograft tumour growth and haematological toxicity in mice.

Fallon J, et al. Villa A, et al. A high-affinity human monoclonal antibody specific to the alternatively spliced EDA domain of fibronectin efficiently targets tumor neo-vasculature in vivo.

Pini A, et al. Design and use of a phage display library. Human antibodies with subnanomolar affinity against a marker of angiogenesis eluted from a two-dimensional gel.

Brack SS, et al. Tumor-targeting properties of novel antibodies specific to the large isoform of tenascin-C.

Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells. Hornick JL, et al. Chimeric CLL-1 antibody fusion proteins containing granulocyte-macrophage colony-stimulating factor or interleukin-2 with specificity for B-cell malignancies exhibit enhanced effector functions while retaining tumor targeting properties.

Dela Cruz JS, et al. Immunity, inflammation, and cancer. Hristodorov D, et al. Macrophage-targeted therapy: CDbased immunotoxins for treatment of chronic inflammatory diseases.

Toxins Basel ; 4 9 — Gutbrodt KL, et al. Antibody-based delivery of interleukin-2 to neovasculature has potent activity against acute myeloid leukemia.

Sci Transl Med. Lo KM, et al. Probst P, et al. Schwager K, et al. J Invest Dermatol. De Luca R, et al. Mol Cancer Ther. Natural killer cell-mediated eradication of neuroblastoma metastases to bone marrow by targeted interleukin-2 therapy.

Yang RK, et al. Intratumoral hu Powrie F, et al. Walmsley M, et al. Interleukin inhibition of the progression of established collagen-induced arthritis.

Arthritis Rheum. Quattrone F, et al. Reprod Sci. The antibody-mediated targeted delivery of interleukin inhibits endometriosis in a syngeneic mouse model.

Hum Reprod. Hu P, et al. J Pharmacol Exp Ther. Penichet ML, et al. Hum Antibodies. Vasuthasawat A, et al.

Targeted immunotherapy using anti-CDinterferon alpha fusion proteins and bortezomib results in synergistic protection against multiple myeloma.

Xuan C, et al. Targeted delivery of interferon-alpha via fusion to anti-CD20 results in potent antitumor activity against B-cell lymphoma.

Frey K, et al. Antibody-based targeting of interferon-alpha to the tumor neovasculature: a critical evaluation.

Integr Biol Camb ; 3 4 — Hemmerle T, et al. The antibody-based targeted delivery of TNF in combination with doxorubicin eradicates sarcomas in mice and confers protective immunity.

Hess C, Neri D. Tumor-targeting properties of novel immunocytokines based on murine IL1beta and IL6.

Hemmerle T, Neri D. The dose-dependent tumor targeting of antibody-IFNgamma fusion proteins reveals an unexpected receptor-trapping mechanism in vivo.

Cancer Immunol Res. The antibody-mediated targeted delivery of interleukin and GM-CSF to the tumor neovasculature inhibits tumor growth and metastasis.

Tumor-targeting properties of antibody-vascular endothelial growth factor fusion proteins. A critical evaluation of the tumor-targeting properties of bispecific antibodies based on quantitative biodistribution data.

Venetz D, et al. Glycosylation profiles determine extravasation and disease-targeting properties of armed antibodies.

Hutmacher C, Neri D. Antibody-cytokine fusion proteins: Biopharmaceuticals with immunomodulatory properties for cancer therapy. Adv Drug Deliv Rev.

Interleukin Biology, Design and Application. Trends Immunol. Benczik M, Gaffen SL. The interleukin IL -2 family cytokines: survival and proliferation signaling pathways in T lymphocytes.

Immunol Invest. Atkins MB, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of patients treated between and J Clin Oncol.

Klapper JA, et al. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma : a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between and Rosenberg SA.

IL the first effective immunotherapy for human cancer. Xiang J, et al. Single-chain antibody variable region-targeted interleukin-2 stimulates T cell killing of human colorectal carcinoma cells.

Immunol Cell Biol. Savage P, et al. A recombinant single-chain antibody interleukin-2 fusion protein. Cell Biophys.

Becker JC, et al. T cell-mediated eradication of murine metastatic melanoma induced by targeted interleukin 2 therapy. J Exp Med. Dolman CS, et al.

Suppression of human prostate carcinoma metastases in severe combined immunodeficient mice by interleukin 2 immunocytokine therapy. Sabzevari H, et al.

A recombinant antibody-interleukin 2 fusion protein suppresses growth of hepatic human neuroblastoma metastases in severe combined immunodeficiency mice.

Albertini MR, et al. Phase II trial of hu A pilot trial of hu Journal of Clinical Oncology. Shusterman S, et al. Antitumor activity of hu A feasibility and phase II study of the hu Gillies SD.

A new platform for constructing antibody-cytokine fusion proteins immunocytokines with improved biological properties and adaptable cytokine activity.

A low-toxicity ILbased immunocytokine retains antitumor activity despite its high degree of IL-2 receptor selectivity.

Gillessen S, et al. A phase I dose-escalation study of the immunocytokine EMD Selectikine in patients with advanced solid tumours.

Eur J Cancer. NHS-IL2 combined with radiotherapy: preclinical rationale and phase Ib trial results in metastatic non-small cell lung cancer following first-line chemotherapy.

J Transl Med. Group M. Management Report. Kaufman HL, et al. Targeted modified IL-2 NHS-IL2, MSB combined with stereotactic body radiation in advanced melanoma patients after progression on ipilimumab: Assessment of safety, clinical, and biologic activity in a phase 2a study.

Klein C, et al. Abstract Tumor-targeted, engineered IL-2 variant IL-2v -based immunocytokines for the immunotherapy of cancer.

Krieg C, et al. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Carmenate T, et al.

Human IL-2 mutein with higher antitumor efficacy than wild type IL Levin AM, et al. Exploiting a natural conformational switch to engineer an interleukin-2 'superkine'.

Merchant AM, et al. An efficient route to human bispecific IgG. Van Brummelen E, et al. Bachanova V, et al.

The immunocytokine F8-IL2 improves the therapeutic performance of sunitinib in a mouse model of renal cell carcinoma. J Urol. Marlind J, et al.

Antibody-mediated delivery of interleukin-2 to the stroma of breast cancer strongly enhances the potency of chemotherapy. Moschetta M, et al.

Paclitaxel enhances therapeutic efficacy of the F8-IL2 immunocytokine to EDA-fibronectin-positive metastatic human melanoma xenografts.

Pretto F, et al. Preclinical evaluation of IL2-based immunocytokines supports their use in combination with dacarbazine, paclitaxel and TNF-based immunotherapy.

Schliemann C, et al. Complete eradication of human B-cell lymphoma xenografts using rituximab in combination with the immunocytokine LIL2.

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