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
  • 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. [email protected].
PMID: 29217732 DOI: 10.1158/2326-6066.CIR-17-0035
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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