Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell–driven tumor immunity
Abstract
MICA and MICB proteins can be expressed on tumors and act as “kill me” signals to the immune system. But tumors often disguise themselves by shedding these proteins, which prevents specialized natural killer (NK) cells from recognizing and destroying the cancer. Ferrari de Andrade et al. engineered antibodies directed against the site responsible for the proteolytic shedding of MICA and MICB (see the Perspective by Cerwenka and Lanier). The approach effectively locked MICA and MICB onto tumors so that NK cells could spot them for elimination. The antibodies exhibited preclinical efficacy in multiple tumor models, including humanized melanoma. Furthermore, the strategy reduced lung cancer metastasis after NK cell–mediated tumor lysis.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 30, 2018
- Source ID
- 10.1126/science.aao0505
Entities
People
- Adrienne M. Luoma
- Bettina Franz
- Charles Yoon
- Christopher J. Harvey
- Daphne Tsoucas
- Deng Pan
- F Stephen Hodi
- Glenn Dranoff
- Guo-cheng Yuan
- Jason W Pyrdol
- Kai Wucherpfennig
- Kenneth F May
- Lucas Ferrari de Andrade
- Rong En Tay
- Sebastian Kobold
- Soumya Badrinath
- Yoshinaga Ito
Organizations
- American Society of Clinical Oncology
- Brigham and Women's Hospital
- Dana–Farber Cancer Institute
- Harvard Medical School
- Melanoma Research Alliance
- National Cancer Institute
- Prostate Cancer Foundation