1. Academic Validation
  2. Peptide Blocking of PD-1/PD-L1 Interaction for Cancer Immunotherapy

Peptide Blocking of PD-1/PD-L1 Interaction for Cancer Immunotherapy

  • Cancer Immunol Res. 2018 Feb;6(2):178-188. doi: 10.1158/2326-6066.CIR-17-0035.
Chunlin Li 1 2 Nengpan Zhang 1 Jundong Zhou 3 Chen Ding 1 4 Yaqing Jin 1 2 Xueyuan Cui 1 5 Kefeng Pu 1 Yimin Zhu 6
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China.
  • 2 University of Chinese Academy of Sciences, Beijing, China.
  • 3 Nanjing Medical University, Affiliated Suzhou Hospital, Department Radio Oncology, Suzhou, China.
  • 4 China Pharmaceutical University, Nanjing, China.
  • 5 Shanghai University, Shanghai, China.
  • 6 CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China. ymzhu2008@sinano.ac.cn.
Abstract

Immunotherapy has become a promising alternative therapeutic approach for Cancer patients. Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been verified to be a successful means for Cancer therapy in clinical trials. mAb targeting PD-L1 has been approved to treat urothelial carcinoma, non-small cell lung Cancer, or Merkel cell carcinoma by the FDA. However, the high cost of the antibody can limit its application. In our study, targeting PD-L1 peptide (TPP-1), which specifically binds to PD-L1 with high affinity, was identified through Bacterial surface display methods. Using a T-cell activation assay and mixed lymphocyte reaction, TPP-1 was verified to interfere with the interaction of PD-1/PD-L1. To examine the inhibitory effect of TPP-1 on tumor growth in vivo, a xenograft mouse model using H460 cells was established. The growth rate of tumor masses in TPP-1 or PD-L1 antibody-treated mice was 56% or 71% lower than that in control peptide-treated mice, respectively, indicating that TPP-1 inhibits, or at least retards, tumor growth. IHC of the tumors showed that IFNγ and granzyme B expression increased in the TPP-1 or PD-L1 antibody-treated groups, indicating that TPP-1 attenuates the inhibitory effect of PD-L1 on T cells and that T cells may get reactivated. On the basis of our data, TPP-1 peptide could work as an alternative to Antibodies for tumor immunotherapy. Cancer Immunol Res; 6(2); 178-88. ©2017 AACR.

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