Th72 - Engineering of Alpha/Beta Selective IL-2 Muteins for Antigen Activated T cells in Solid Tumors

Thursday, June 23, 2022

6:15 PM – 7:30 PM PT

Presenting Author(s)

SV

Sandro Vivona, PhD

Director of Biochemistry and Biophysics
Synthekine
Menlo Park, California, United States

Co-Author(s)

JE

Jan Emmerich, n/a

synthekine
Menlo Park, California, United States
rR

romina Renier, n/a

Synthekine
Menlo Park, California, United States
nr

nav ratti, n/a

Synthekine
menlo Park, California, United States
SM

Scott McCauley, n/a

Synthekine
Menlo Park, California, United States
BJ

Bhargavi Jayaraman, n/a

Synthekine
menlo park, California, United States
mB

michele Bauer, n/a

Synthekine
menlo park, California, United States
mS

marie Semana, n/a

Synthekine
menlo park, California, United States
RD

Rene De Waal Malefyt, n/a

Synthekine
Menlo Park, California, United States
RK

Rob Kastelein, n/a

Synthekine
Menlo Park, California, United States
MO

Martin Oft, n/a

Synthekine
Menlo Park, California, United States
PL

Patrick Lupardus, n/a

Synthekine
Menlo Park, California, United States

Interleukin-2 (IL-2) potently stimulates cytotoxicity, survival, and the proliferation of T and NK-cells, but it also stimulates regulatory T-cells (Treg). High dose IL-2 monotherapy induces complete responses in cancer patients, but severe acute toxicities including capillary leak syndrome (CLS) limit its application. Here we describe new IL-2-partial agonists selective for the high affinity, trimeric IL-2 receptor, IL-2Ra/b/g (CD25/122/132) expressed on activated T cells. These a/b-IL2 do not activate CD25^- NK cells allowing continuous treatment without acute toxicities in non-human primates and mice. This enables improved efficacy and single agent complete responses in mouse tumor models and a significant increase of tumor infiltrating CD8+ T-cells (TIL) and the TIL/Treg ratio in tumors, compared to wt or IL-2Rb/g-selective IL-2s. a/b-IL2 may improve clinical success of IL-2 in cancer patients.