By Witold Lasek, Radoslaw Zagozdzon, Marek Jakóbisiak
This e-book discusses the immunotherapeutic power of Interleukin 12 within the context of medical oncology, in addition to antitumor results proven in preclinical experiences and scientific trials in melanoma immunotherapy. as a result of its skill to turn on either innate (NK cells) and adaptive (cytotoxic T lymphocytes) immunities, Interleukin 12 (IL-12) has been considered as a promising candidate for tumor immunotherapy. besides the fact that, regardless of the encouraging ends up in animal types, basically very modest antitumor results were proven in early scientific trials. lately, numerous medical reports were initiated during which IL-12 was once utilized as an adjuvant in melanoma vaccines, in gene remedy together with locoregional injections of IL-12 plasmid, and within the type of tumor-targeting immunocytokines (IL-12 fused to monoclonal antibodies).
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Sample text
1999). 1 Early Clinical Trials 45 earlier. c. in 28-day cycles on days 1, 8, and 15) (Motzer et al. 1998). A similar trial with escalating doses of IL-12 was conducted with melanoma patients (Bajetta et al. 1998). Genetics Institute applied “more aggressive” dosing regimen: consecutive intravenous daily injections of IL-12. In a phase I trial, maximal tolerated dose of 500 ng/kg per day was determined. Unexpectedly, this dose was found toxic in the phase II trial and severe side effects of the treatment developed in 12 of 17 enrolled patients leading to death of two patients.
2014). Antitumor effects of IL-12 were evaluated in various treatment schedules: intravenous (Atkins et al. 1997; Robertson et al. 1999; Gollob et al. 2000) versus subcutaneous (Bajetta et al. 1998; Motzer et al. 1998) or even intraperitoneal application (Lenzi et al. 2002), daily—5 consecutive injections every three weeks (Atkins et al. 1997; Robertson et al. 1999; Wadler et al. 2004), or at 1 (Bajetta et al. 1998; Motzer et al. 1998; Haicheur et al. 2000), 2 (Gollob et al. 2000) or 3 (Portielje et al.
Very promising and actively explored IL-12-based approach in preclinical studies (and also in current clinical trials) is improving adoptive T cell therapy by transduction of effector cells with IL-12 gene. There have been several variants of this approach in recent investigations: – application of TCR-engineered T cells, targeting tumor-specific antigen, expressing independently IL-12 (Zhang et al. 2011; Kerkar et al. 2013; Galvan et al. 2015); – treatment with IL-12-secreting T cells expressing tumor-targeted chimeric antigen receptors (CAR) (Chmielewski et al.