Dr Christian Klein talks to ecancertv at the 1st Immunotherapy of Cancer Conference ( ITOC ) meeting in Munich.

He describes a novel class of monomeric tumour-targeted immunocytokines that comprise a single IL-2 variant (IL2v) with abolished CD25 binding that is fused to the C-terminus of a tumour specific antibody with a heterodimeric Fc devoid of FcgR and C1q binding.

For tumour targeting, human/humanized high affinity antibodies against CEA or FAP were selected. CEA- and FAP-IL2v activity was tested on effector cells by assessing the activation of P-STAT5, cell proliferation, sensitivity to Fas-induced apoptosis, expression of activation markers and cytokine release upon treatment.

Compared to classical IL-2-based immunocytokines, CEA-IL2v and FAP-IL2v demonstrate superior safety, PK and tumour targeting due to abolished CD25 binding, monovalency and high-affinity to tumour antigens while failing to preferentially induce Tregs. CEA-IL2v and FAP-IL2v retain the capacity to activate and expand NK and CD8 effector T cells both in the periphery and tumour microenvironment supporting their further nonclinical and clinical investigation for immunotherapy of cancer.