https://www.nature.com/articles/s41586-024-08507-5
"Personalized cancer vaccines (PCVs) can generate circulating immune responses
against predicted neoantigens. However, whether such responses can target
cancer driver mutations, lead to immune recognition of a patient’s tumour and
result in clinical activity are largely unknown. These questions are of
particular interest for patients who have tumours with a low mutational burden.
Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766)
to test a neoantigen-targeting PCV in patients with high-risk, fully resected
clear cell renal cell carcinoma (RCC; stage III or IV) with or without
ipilimumab administered adjacent to the vaccine. At a median follow-up of
40.2 months after surgery, none of the 9 participants enrolled in the study had
a recurrence of RCC. No dose-limiting toxicities were observed. All patients
generated T cell immune responses against the PCV antigens, including to RCC
driver mutations in
VHL,
PBRM1,
BAP1,
KDM5C and
PIK3CA. Following
vaccination, there was a durable expansion of peripheral T cell clones.
Moreover, T cell reactivity against autologous tumours was detected in seven
out of nine patients. Our results demonstrate that neoantigen-targeting PCVs in
high-risk RCC are highly immunogenic, capable of targeting key driver mutations
and can induce antitumour immunity. These observations, in conjunction with the
absence of recurrence in all nine vaccinated patients, highlights the promise
of PCVs as effective adjuvant therapy in RCC."
Via mhoye and Susan ****
Cheers,
*** Xanni ***
--
mailto:xanni@xanadu.net Andrew Pam
http://xanadu.com.au/ Chief Scientist, Xanadu
https://glasswings.com.au/ Partner, Glass Wings
https://sericyb.com.au/ Manager, Serious Cybernetics
