Mark Yarchoan, Associate Professor at Johns Hopkins Hospital, shared a post on X:
“Excited to share our newest study in Nature Medicine on a vaccine targeting the recurrent fusion DNAJ-PKAc in fibrolamellar carcinoma (FLC), a rare liver cancer affecting kids and young adults.”
FLC is driven by a currently “undruggable” fusion protein, DNAJ-PKAc. The fusion is intronic → creates a nearly universal neoantigen for FLC We tested a 24aa vaccine spanning the fusion +IPI/NIVO (NCT04248569).
Among 12 patients completing the 10-week priming phase:
9/12 with DNAJ-PKAc T cell responses
3/12 achieved partial responses – 5 pts (all 3 responders and 2 SD pts) in CR years later Responders all had immune responses, suggesting “on-target” vaccine-mediated immunity.
Similar to other peptide vaccines, most of the T cell responses to our vaccine were CD4 T cell responses.
TCR profiling revealed multiple class II-restricted TCRs targeting DNAJ-PKAc. We hope to bring these forward at TCR-T therapy in the future.
No patient lost expression of the target antigen (c/w oncogenic addiction) and no loss of HLA expression, providing support for oncogene-targeted CD4 responses. One patient who progressed responded to anti-CTLA4 rechallenge – suggests exhaustion mech of res.
This work was primarily funded by the NCI, NIH, with support from the fibrolamellar cancer foundation (FCF) and BMS. Thank you to our patients and research teams!”
Title: A therapeutic peptide vaccine for fibrolamellar hepatocellular carcinoma: a phase 1 trial
Authors: Marina Baretti, Allison M. Kirk, Brian H. Ladle, Zeal Kamdar, Kayla J. Bendinelli, Won Jin Ho, Samir Adhikari, Nicholas A. Clark, Balaji Sundararaman, Hao Wang, Heng-Chung Kung, Jeric Hernandez, Hanfei Qi, Sarah M. Shin, Alexei Hernandez, Mari Nakazawa, Stefan A. Schattgen, Jeremy Chase Crawford, Mark Furth, Robert A. Anders, Chris Thoburn, Neeha Zaidi, Amanda L. Huff, Julie Nauroth, Elizabeth Jaffee, Mikhail V. Pogorelyy, Paul G. Thomas, Mark Yarchoan
Read The Full Article at Nature Medicine.
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