Immunocytokines: a novel class of products for the treatment of chronic inflammation and autoimmune conditions

Abstract

Antibody-cytokine fusion proteins, often referred to as immunocytokines, represent a novel class of biopharmaceutical agents that combine the disease-homing activity of certain antibodies with the immunomodulatory properties of cytokine payloads. Originally, immunocytokines were mainly developed for cancer therapy applications. More recently, however, the use of antiinflammatory cytokines for the treatment of chronic inflammatory conditions and to treat autoimmune diseases has been considered. This review analyzes basic principles in the design of immunocytokines and describes the most advanced products in preclinical and clinical development.

Tumor angiogenesis revisited: Regulators and clinical implications

“…An alternative therapeutic strategy to angiogenesis inhibitors, which block neovascularization, is represented by “vascular targeting,” which relies on mAbs that recognize specific markers on newly formed blood vessels or in the stroma surrounding these vessels. These Abs selectively deliver potent therapeutic payloads (such as drugs, cytokines, radionuclides, photosensitizers, and toxins) to disease sites where neoangiogenesis takes place …”

“…These Abs selectively deliver potent therapeutic payloads (such as drugs, cytokines, radionuclides, photosensitizers, and toxins) to disease sites where neoangiogenesis takes place. 419,420 Several antigens have been identified using immunohistochemical, proteomic, or transcriptomic screenings. 421,422 Well-known examples are represented by the alternatively spliced extradomains A and B of fibronectin, as well as the extradomain A1 of tenascin-C.…”

Comparative evaluation of bolus and fractionated administration modalities for two antibody-cytokine fusions in immunocompetent tumor-bearing mice

“…The successful treatment of a growing number of tumor types with immune checkpoint inhibitors [1][2][3][4][5][6][7][8][9] has stimulated the interest in the exploration of alternative and complementary approaches for the selective boosting of T cell and NK cell activity against cancer. For many years, pro-inflammatory cytokines have been considered as a promising class of biopharmaceuticals for immunotherapy applications, but the practical applicability of cytokine therapies has been limited by severe toxicity at low doses, preventing escalation to therapeutically active regimens [10,11]. In spite of these limitations, some products have gained marketing authorization and have provided a therapeutic benefit for a small proportion of patients.…”

The immunocytokine L19-TNF eradicates Sarcomas in combination with Chemotherapy agents or with immune check-point inhibitors

“…The use of recombinant cytokines for cancer therapy may cause substantial toxicities already at low doses, therefore limiting their clinical use and preventing escalation to therapeutically active dose regimens [23][24][25][26]. To increase the therapeutic efficacy of cytokine payloads, the generation of fusion proteins with tumor-homing antibodies has been proposed.…”

“…To increase the therapeutic efficacy of cytokine payloads, the generation of fusion proteins with tumor-homing antibodies has been proposed. Antibodycytokine fusion proteins (also termed "immunocytokines") are capable of increasing the therapeutic index of the corresponding cytokine payload, as results of a selective localization at the site of disease [24][25][26][27][28].…”