Healthy donor T cell receptors expand functional neoantigen recognition beyond patient vaccination
Year: 2026
Type: article
Abstract: T cells, emphasizing the critical need for comprehensive functional validation before patient vaccination. Here, we provide a direct comparison of neoantigen-specific T cell responses between vaccinated patients with cancer and HLA-matched healthy donors. Despite vaccination, patient-derived T cells recognized only a small fraction of predicted neoantigens, whereas healthy donor T cells consistently exhibited broader and more robust neoantigen reactivity. Furthermore, we successfully expanded neoantigen-specific T cells from allogeneic donors, revealing that their T cell receptors (TCRs) can recognize targets that the patient's own T cells fail to engage with, partly due to poor T cell fitness. Collectively, these results indicate that cancer vaccines may be insufficient to overcome intrinsic defects in patient-derived T cell responses, supporting the use of healthy donor-derived TCRs as a complementary approach.
Source: Science Advances
Authors: Hong Kai Teo, Shuting Han, Thamizhanban Manoharan, Yi Ren, Cyrus Zai Ming Cheng, Soon Chai Loo, Zhewang Lin, Jiaqi Li, Who-Whong Wang, Si-Lin Koo, Malini Rethnam, Choon Kong Yap, Bei-En Siew, Gwyneth Shook-Ting Soon, Wai-Kit Cheong, Kai-Yin Lee, Ian Jse-Wei Tan, Bettina Lieske, Ker-Kan Tan, Han Chong Toh, Iain Bee Huat Tan, Gloryn Chia
Institutions: National University of Singapore, Institute for Health Innovation & Technology, National Cancer Centre Singapore, Agency for Science, Technology and Research, Genome Institute of Singapore, National University Hospital, National University Health System, SingHealth Duke-NUS Academic Medical Centre, Duke-NUS Medical School
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Award: G5835809272
OpenAlex ID: W7154712240