AUTOANTIBODIES AS BIOMARKER OF PARANEOPLASTIC  ENCEPHALITIS ASSOCIATED WITH TESTICULAR CANCER

AUTOANTIBODIES AS BIOMARKER OF PARANEOPLASTIC  ENCEPHALITIS ASSOCIATED WITH TESTICULAR CANCER

Researchers at the Chan Zuckerberg Biohub, UCSF and the Mayo Clinic have discovered a novel biomarker for an autoimmune disease that affects patients with testicular cancer.  The disease, known as “testicular cancer-associated paraneoplastic encephalitis,” can cause severe neurological symptoms.  The symptoms include loss of limb control, eye movement, and in some cases, speech.  The disease begins with testicular cancer, which in some cases causes the immune system to attack the brain.  Affected patients are often misdiagnosed and appropriate treatment is delayed.

Stage of Research

The inventors have identified a highly specific and unique biomarker for paraneoplastic encephalitis using programmable phage display.  Using this powerful tool, the researchers evaluated cerebrospinal fluid from a 37-year-old patient who had a history of testicular cancer and debilitating neurological symptoms, including vertigo, imbalance and slurred speech. The enhanced phage technology identified autoantibodies targeting Kelch-like protein 11 (KLHL11) found in the testes and parts of the brain. These results were correlated and validated with additional patient samples.

Applications

  • A stand-alone diagnostic for testicular cancer-associated paraneoplastic encephalitis
  • A diagnostic panel component for cancer and related autoimmune disease

Advantages

  • Autoantibodies to KLHL11 are a specific biomarker for testicular cancer-associated paraneoplastic encephalitis
  • Until the discovery of Kelch11 autoantibodies, there was no diagnostic marker for this disease
  • Accurate diagnosis now allows appropriate and timely treatment

Stage of Development

Research – in vitro

Publications

Mandel-Brehm C, Dubey D, Kryzer TJ, O’Donovan BD., Tran B, Vazquez SE, Sample HA, Zorn KC, Khan LM, Bledsoe IO, McKeon A, Pleasure SJ, Lennon VA, DeRisi JL, Wilson MR, Pittock, SJ. Kelch-like Protein 11 Seminoma-associated Paraneoplastic Encephalitis. N Engl J Med 381:47-54 (2019)

PCT publication WO2020/190700

Related Web Links

https://derisilab.ucsf.edu

Keywords

Autoantibody, diagnosis, antibody, neurology, testicular cancer, KLHL11

Reference

Chan Zuckerberg CZB-118F, UCSF SF2018-036, Mayo Ventures 2018-354

Patent Information:
For Information, Contact:
CZBiohub Admin
Inteum Hosted Admin
CZ Biohub
ip@czbiohub.org
Inventors:
Joseph DeRisi
Michael Wilson
Caleigh Mandel-Brehm
Brian O'Donovan
Sean Pittock
Divyanshu Dubey
Thomas Kryzer
Vanda Lennon
Andrew McKeon
Keywords:
Antibody
Autoantibody
Diagnosis
KLHL11
Neurology
Testicular Cancer