Euro-Global Conference on Biotechnology and Bioengineering

September 06-08, 2021 | Online Event

September 06-08, 2021 | Online Event
ECBB 2021

Yan Zhang

Speaker at Biotechnology and Bioengineering 2021 - Yan Zhang
Shanghai Jiao Tong University, China
Title : The immunogenicity and anti-tumor efficacy of a rationally designed neoantigen vaccine for B16F10 mouse melanoma


Tumor neoantigens are ideal targets for cancer immunotherapy as they are recognized by host immune system as foreigners and can elicit tumor-specific immune responses. However, existing strategies utilizing RNA or long peptides for the neoantigen vaccines render limited immune responses since only 20%-30% of neoantigens predicted in silico to bind MHC I molecules are capable of eliciting immune responses with the majority of responding T cells are CD4+. Therefore, it warrants further exploration to enhance neoantigen-specific CD8+ T cells responses. Since neoantigens are naturally weak antigens, we asked whether foreign T help epitopes could enhance their immunogenicity. In present study, we chose four weak B16F10 neoantigens as vaccine targets, and fused them to the transmembrane domain of diphtheria toxin, namely DTT-neoAg. Strikingly, the vaccine elicited anti-tumor CD8+ T cells responses and enhanced tumor infiltration of both T cells and NK cells. Impressively, DTT-neoAg vaccine significantly deterred tumor growth with the inhibition rate reached 88% in the preventive model and 100% in therapeutic model at low dose of tumor challenge. Furthermore, after second challenge with higher dose of tumor cells, 33.3% of the immunized mice remain tumor-free for 6 months in the therapeutic model. Because DTT is a nontoxic domain of diphtheria toxin, it may be not of great concern in terms of safety as a Th epitope provider. Thus the fusion strategy employed by this study may become a feasible and powerful approach for development of personalized cancer vaccine.

Presentation Learning Outcome

  • Our DTT-neoAg vacccine significantly expand the pool of effective vaccine targets, which should benefit cancer patients with intermediate/low mutation burdens such as Ovary cancer, Prostate cancer, low grade Glioma, Chronic lymphocytic leukemia, and Acute myeloid leukemia.
  • The strategy of using DTT to enhance the immune response of weak immunogenic neoantigen could be applied to any weakly immunogenic antigen.
  • In our novel neoantigen vaccine design, neoantigen targets selection only needs to consider that mutations are non-synonymous and that the corresponding proteins are highly expressed. Immunogenicity prediction and immune response verification can be skipped. This will simplify the neoantigen screening process.
  • Since DTT is a non-toxic domain of the toxin molecule, its safety would not be of great concern as a vaccine adjuvant. It will be more feasible for development of personalized cancer vaccines in clinical trials.


Dr. Yan Zhang studied Biochemistry and Molecular Biology at Nankai University, and was fortunate to study in the research group of Zihe Rao academician and graduated as MS in 2013. She then joined the research group of Prof. Rongxiu Li at State Key Laboratory of Microbial metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University. She will receive her PhD degree in 2020 at the same institution. She has published 3 research articles in SCI (E) journals.