Details

Autor(en) / Beteiligte

• Li, Chunlin
• Zhang, Nengpan
• Zhou, Jundong
• Ding, Chen
• Jin, Yaqing
• Cui, Xueyuan
• Pu, Kefeng
• Zhu, Yimin

Titel

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

Ist Teil von

• Cancer immunology research, 2018-02, Vol.6 (2), p.178-188

Ort / Verlag

United States

Erscheinungsjahr

2018

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 , 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. .