Thématique :
- Foie
Originalité :
Très original
Solidité :
A confirmer
Doit faire évoluer notre pratique :
Pas encore
Nom du veilleur :
Professeur Jean-Marie PERON
Coup de coeur :
  2017 Feb. pii: S0016-5085(17)30132-4.  
  doi: 10.1053/j.gastro.2017.02.001  
  Association Between High-avidity T-cell Receptors, Induced by Alpha Fetoprotein-derived Peptides, and Anti-tumor Effects in Patients with Hepatocellular Carcinoma.  
  Nakagawa H, Mizukoshi E, Kobayashi E, Tamai T, Hamana H, Ozawa T, Kishi H, Kitahara M, Yamashita T, Arai K, Terashima T, Iida N, Fushimi K, Muraguchi A, Kaneko S  



Levels of alpha fetoprotein (AFP) are measured for surveillance and diagnosis of hepatocellular carcinoma (HCC). We performed a phase 1 trial to evaluate the safety and efficacy of AFP-derived peptides as an anti-tumor vaccine for patients with advanced HCC, and characterized induction of AFP-specific T-cell receptors (TCRs).


We performed a prospective study, of 15 patients with HCC seen at Kanazawa University Hospital in Japan from March 2010 through March 2012. Each patient was given a subcutaneous injection of 3 mg of AFP-derived peptides (AFP357 and AFP403) in an emulsion with incomplete Freund's adjuvant every other week for at least 6 weeks. Patients were evaluated every 8 weeks by radiologic imaging; adverse events and toxicities were categorized and graded using the common terminology criteria for adverse events. Criteria for discontinuation included unacceptable toxicities and disease progression defined as progressive disease using the Response Evaluation Criteria In Solid Tumors criteria. Patients' immune responses were monitored using an interferon-gamma enzyme-linked immunospot assay. Peptide-specific TCRs were assessed using a rapid TCR cloning and evaluation system. The observation period was 730 days. A complete response was defined as the disappearance of all tumors; stable disease was defined as tumors whose total diameter ranged from less than 30% to more than 20% of the baseline measurement, without new lesions.


We did not observe any serious adverse reactions to the peptides, which were well tolerated. Of the 15 patients who received at least 3 injections, 5 (33%) had an immune response to the peptides. One of the 15 patients had a complete response and disease stabilized in 8 patients. In 4 of the 15 patients, we detected AFP357-specific CD8 T-cells; we cloned 14 different TCRs with different avidities for the peptide. A TCR with the highest avidity was observed in the patient who achieved a complete response for more than 2 years.


In a phase 1 trial, administration of AFP-derived peptides to 15 patients with HCC did not cause adverse events and produced T-cells with receptors that reacted to the peptides; 1 patient had a complete response and tumor growth slowed in 8 patients. T-cells from the patient with a complete response expressed a highly functional TCR induced by the peptide vaccines. UMIN-CTR no: UMIN000003514.


Question posée
Immunothérapie du CHC par administration de peptides stimulant une réponse immune contre les cellules exprimant l’AFP.
Question posée
Etude de phase 1, montrant la bonne tolérance de cette approche d’immunothérapie. Cinq patients ont développé une réponse immune spécifique et 1, une réponse complète.

Une piste d’immunothérapie intéressante ciblant les patients avec des tumeurs exprimant l’AFP. A confirmer sur une phase 2.