Towards a more patient-centric assessment of immunogenicity for low-risk biologics in immuno-oncology clinical trials
Hassanein M, Wang Y, Yin D & Baltrukonis D | Bioanalysis, 13(17), 1309 – 1312, (2021)
Keywords: • biotherapeutic • clinical impact • immunogenicity • immunotherapies • incidence of antidrug antibodies • IO • monoclonal antibodies • neutralizing antibodies • reporting
Immune check point inhibitors & their clinical immunogenicity profile; a decade in the making
The approval of ipilimumab, the first cancer immunotherapy for patients with advanced melanoma in 2011 ushered a new dawn for cancer treatment and provided additional therapeutic option for millions of patients around the world [1,2]. A decade later, cancer immunotherapies, also referred to as immuno-oncology (IO) agents, are now viewed as the ‘fifth pillar’ of cancer therapy, joining the standard of care treatments that include surgery, chemotherapy, radiation and targeted therapy [3]. The impressive clinical success of immune check point inhibitors (ICIs), a subclass of cancer immunotherapies, led to the approval of seven anti-PD-1/PD-L1 and one anti-CTLA-4 monoclonal antibodies (mAbs) with many more agents in the drug pipeline [4]. All approved ICIs to date are either humanized or fully human mAbs, which are typically classified as low risk molecules [4–7]. This has been long recognized by the European Medicines Agency (EMA) and in its 2012 guideline on immunogenicity assessment of mAbs intended for in vivo clinical use, which states that “mAbs are not expected to induce antibodies that cross-react and neutralize an endogenous counterpart (as can occur with EPO)” [8].
