One thing I realized at SITC this year was that not many people know (or care?) about the difference between the IL-15s now being tested in trials. There are: the recombinant human (rh)IL-15, the IL-15/IL-15Ralpha heterodimer (hetIL-15), and ALT-803, the “super-agonist”. You’re better of reading a more comprehensive review, but some highlights are below.
- The simplest, oldest, and seemingly most potent is the plain vanilla rhIL-15.
- Four dosing strategies have so far been tested: bolus (too toxic, published), subcutaneous (OK, about as good as ALT-803 in increasing NKs and CD8+ T cells, also published), 10-day continuous infusion (the most potent, but who wants to sit in a hospital for 10 days, should be published soon), and a 5-day infusion (same 40-fold increase in NK numbers in half the time! presented at SITC)
- None of the patients in any of the regimens had a RECIST response, but most mounted an impressive lymphocytosis, leading to several planned combination trials
It is available for investigator-initiated studies through CTEP. They will also give a few vials for preclinical studies.
Novartis owns hetIL-15, and is running the phase I alone and in combination with their anti-PD-1. Nothing published, but I’ll have more to say about it next year.
ALT-803 is an IL-15/IL-15Ralpha heterodimer blessed with a single point mutation which confers upon it both increased binding to the common gamma chain, and validity to the claim of new IP.
- It is the only one shown to have efficacy as a single agent (though not in solid tumors), and the only one to be part of a published and/or presented combination (with nivolumab in NSCLC, and with rituximab in FL).
- What’s presented so far makes it less potent than rhIL-15 in increasing cell counts, but more convenient to give: via once-weekly subcutaneous injections for an 8-fold increase in NKs.
- The company, Altor Biosciences, had been fairly open to IITs — one of them is currently open at NCI’s GU Malignancies Branch — but maybe not so much since being acquired in August 2018 by NantCell, a Patrick Soon-Shiong company.
There’s more, of course, but I’ll end instead with another plug for our review of cytokines in cancer therapy.