Armed antibodies for cancer treatment: a promising tool in a changing era

Abstract

Advances in the understanding of tumor immunology and molecular biology of melanoma cells have favored a larger application of immunotherapy and targeted therapies in the clinic. Several selective mutant gene inhibitors and immunomodulating antibodies have been reported to improve overall survival or progression-free survival in metastatic melanoma patients. However, despite impressive initial responses, patients treated with selective inhibitors relapse quickly, and toxicities associated to the use of immunomodulating antibodies are not easily manageable. In this sense, the concept of using antibodies as delivery vehicles for the preferential in vivo localization of the drug at the site of disease with reduction of side effects has raised particular interest. Antibody-cytokine fusion proteins (termed immunocytokines) represent a new simple and effective way to deliver the immunomodulatory payload at the tumor site, with the aim of inducing both local and systemic antitumoral immune responses and limiting systemic toxicities. Several clinical trials have been conducted and are actually ongoing with different immunocytokines, in several tumor histotypes. In metastatic melanoma patients, different drug delivery modalities such as systemic, loco-regional and intratumoral are under investigation. In this review, the rationale for the use of L19-IL2 and L19-TNF, two clinical stage immunocytokines produced by the Philogen group, as well as opportunities for their future development will be discussed.

Intralesional PV‐10 for in‐transit melanoma—A single‐center experience

“…With the introduction of novel systemic agents targeting immune checkpoints (ipilimumab, pembrolizumab, nivolumab), and mutations in the MAP kinase pathway (dabrafenib and trametinib), the treatment options for patients with unresectable metastases have increased and the prognosis for these patients has significantly improved [6][7][8][16][17][18][19]. However, these agents may be associated with significant toxicity and in the case of PD-1 targeted therapy require frequent hospital visits for infusions [16].…”

“…The effective treatment options for metastatic and locoregional inoperable disease melanoma have rapidly improved over the last 5 years [6][7][8][16][17][18][19]. With the introduction of novel systemic agents targeting immune checkpoints (ipilimumab, pembrolizumab, nivolumab), and mutations in the MAP kinase pathway (dabrafenib and trametinib), the treatment options for patients with unresectable metastases have increased and the prognosis for these patients has significantly improved [6][7][8][16][17][18][19].…”

Tumor-directed immunotherapy can generate tumor-specific T cell responses through localized co-stimulation

“…Antibodies with higher isoelectric point may be retained in the acidic environment. Another promising approach would be to generate antibodies that preferentially bind their target at lower pH, designing the antibody binding site to depend on the protonated form of histidine residues [37, 39]. Further, a class of proteolytically triggered antibodies engineered to remain inert until enzymatically activated in the tumor microenvironment has been described [40].…”

WOMEN IN CANCER THEMATIC REVIEW: Ovarian cancer–peritoneal cell interactions promote extracellular matrix processing

“…Both L19-IL2 (Darleukin) and L19-TNF (Fibromun) have shown promising results in phase I clinical trials in patients with advanced cancer and are currently being evaluated in further phase I/II trials (Danielli et al 2015).…”