Neoleukin-2 enhances anti-tumour immunity downstream of peptide vaccination targeted by an anti-MHC class II VHH
Abstract
Cancer-specific mutations can lead to peptides of unique sequence presented on MHC class I to CD8 T cells. These neoantigens can be potent tumour-rejection antigens, appear to be the driving force behind responsiveness to anti-CTLA-4 and anti-PD1/L1-based therapies and have been used to develop personalized vaccines. The platform for delivering neoantigen-based vaccines has varied, and further optimization of both platform and adjuvant will be necessary to achieve scalable vaccine products that are therapeutically effective at a reasonable cost. Here, we developed a platform for testing potential CD8 T cell tumour vaccine candidates. We used a high-affinity alpaca-derived VHH against MHC class II to deliver peptides to professional antigen-presenting cells. We show in vitro and in vivo that peptides derived from the model antigen ovalbumin are better able to activate naive ovalbumin-specific CD8 T cells when conjugated to an MHC class II-specific VHH when compared with an irrelevant control VHH. We then used the VHH-peptide platform to evaluate a panel of candidate neoantigens in vivo in a mouse model of pancreatic cancer. None of the candidate neoantigens tested led to protection from tumour challenge; however, we were able to show vaccine-induced CD8 T cell responses to a melanoma self-antigen that was augmented by combination therapy with the synthetic cytokine mimetic Neo2/15.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 01, 2020
- Source ID
- 10.1098/rsob.190235
Entities
People
- Amelia Mitchell-gears
- David M. Knipe
- Hee-jin Jeong
- Hidde Ploegh
- Jessica R. Ingram
- Kevin Zhangxu
- Lestat R. Ali
- Md Aladdin Bhuiyan
- Michael Dougan
- Michael J. Walsh
- Patrick T. Bruck
- Stephanie J. Crowley
- Stephanie K Dougan
Organizations
- Boston Children's Hospital
- Dana–Farber Cancer Institute
- Harvard Medical School
- Hongik University
- National Institutes of Health
- United States Department of Defense
- University of Leeds