On June 12, 2023 Parthenon Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), reported that the Journal for ImmunoTherapy of Cancer (JITC) has published results from an international panel of cancer experts convened to provide an initial consensus on the role of immune exclusion in cancer (Press release, Parthenon Therapeutics, JUN 12, 2023, View Source [SID1234632688]).
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The article "Developing a Definition of Immune Exclusion in Cancer: Results of a Modified Delphi Workshop," identifies key characteristics of and issues relevant to the role immune exclusion plays in resistance to checkpoint therapy and is now available online. The work described in the paper was performed in collaboration with multiple US and international academic institutions.
"Immune exclusion until now has not had a well-defined profile, but we know it exists across multiple tumor types," said J. Paul Eder, MD, Chief Medical Officer of Parthenon Therapeutics. "In collaboration with academic leaders, Parthenon is pioneering how to recognize and define immune exclusion in cancer and understand the mechanisms underlying it. By modulating the tumor microenvironment and breaking down the barrier that tumors construct to protect them from an immune attack, we think we can overcome immune exclusion and thus, improve patient outcomes."
Parthenon recently initiated a Phase 1 trial for its lead candidate PRTH-101 first-in-human clinical trial in patients with immune-excluded solid tumors (NCT05753722).
About PRTH-101
PRTH-101 is a therapeutic antibody that specifically binds to and blocks DDR1, a protein expressed on tumor cells that binds collagen to make a minimally permeable physical barrier that blocks immune cells from interacting with and attacking tumor cells. Thus, these "immune cell-excluded" solid tumors are resistant to attack by the immune system (as well as other existing therapies). By disabling DDR1, the collagen fibers lose alignment and loosen, creating gaps in the tumor barrier, thus allowing T-cells to enter and naturally attack the tumor. The creation of DDR1-directed collagen alignment does not appear to have a normal physiological surrogate and may therefore be unique to pathologies such as neoplasia, potentially allowing for relatively safe interventions. Thus, blockade of DDR1 represents a unique and "orthogonal" approach to stimulating the immune-based antitumor activity, and such blockade shows both single agent anti-tumor activity as well as marked augmentation of immunity enhanced by PD-1 blockade.
Tumor types which show particularly high levels of DDR1-associated collagen barriers include colorectal, ovarian, and non-small cell lung cancer. Currently, there are no approved drugs that target DDR1.